<i>Background</i>. To identify parameters based on dual-imaging <sup>18</sup>F-AlF-NOTA-octreotide (<sup>18</sup>F-OC) and 18-fluorodeoxyglucose (<sup>18</sup>F-FDG) positron emission tomography (PET) for predicting the prognosis of neuroendocrine neoplasms (NENs). <i>Materials and Methods</i>. Sixty-six patients (age: <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="39.544pt" style="vertical-align:-0.3499298pt" id="M1" height="9.65783pt" version="1.1" viewBox="-0.0498162 -9.3079 39.544 9.65783"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-110" d="M797 0V26C739 32 732 36 732 103V296C732 394 682 449 605 449C576 449 550 437 529 423C504 407 475 389 446 366C425 418 382 449 334 449C303 449 279 437 253 421C222 403 201 385 180 371V452C135 432 85 419 41 411V388C99 379 102 374 102 310V103C102 38 93 32 27 26V0H238V26C189 32 180 38 180 103V338C210 363 250 390 289 390C351 390 377 348 377 275V103C377 37 368 32 306 26V0H520V26C465 32 456 38 456 101V296C456 314 455 326 453 338C491 369 529 390 565 390C628 390 653 345 653 274V107C653 36 642 32 583 26V0H797Z"/></g><g transform="matrix(.013,0,0,-0.013,10.595,0)"><path id="g190-102" d="M380 106C343 72 306 56 265 56C195 56 116 112 115 248C235 252 361 262 377 265C396 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-12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g><g transform="matrix(.013,0,0,-0.013,24.59,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.975pt" style="vertical-align:-0.3499298pt" height="8.69875pt" version="1.1" viewBox="35.076183799999995 -8.34882 21.975 8.69875"><g transform="matrix(.013,0,0,-0.013,35.126,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,41.366,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,47.606,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,50.57,0)"><use xlink:href="#g113-57"/></g></svg></span> years) who underwent both <sup>18</sup>F-OC and <sup>18</sup>F-FDG PET/CT imaging were enrolled in our retrospective study. The following PET parameters were measured: the maximum standardized uptake value (SUV<sub>max</sub>) and the volumetric parameters—<sup>18</sup>F-OC SSR-derived tumor volume (TV) and somatostatin receptor expression (SRE, TV multiplied by the mean standardized uptake value (SUV<sub>mean</sub>)) and the <sup>18</sup>F-FDG-derived multiple tumor volume (MTV) and tumor lesion glycolysis (TLG). The NETPET grade based on dual-imaging PET images was assessed. Progression-free survival (PFS) was set as an endpoint. Univariate and multivariate survival analyses were performed for PET parameters and clinical tumor data. <i>Results</i>. In the univariate survival analyses of clinical information, PFS was significantly associated with age (>45.5 vs ≤45.5, years, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M3" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g></svg>)</span></span> and the presence of bone metastases (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.2064009pt" id="M4" height="8.8423pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 8.8423"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.2064009pt" height="8.8423pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 8.8423"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-53"/></g></svg>).</span></span> Higher values for the <sup>18</sup>F-FDG and <sup>18</sup>F-OC volumetric parameters and the NETPET grade were adverse factors for PFS according to the dual-imaging PET parameters. In the multivariate survival analysis, the NETPET grade and SRE were predictors of PFS in NEN patients. <i>Conclusion</i>. The NETPET grade is a potential noninvasive prognostic biomarker for NENs.

Jiale Hou

Tingting Long

Yi Yang

Dengming Chen

Shuo Hu

The Potential Prognostic Value of Dual-Imaging PET Parameters Based on <sup>18</sup>F-FDG and <sup>18</sup>F-OC for Neuroendocrine Neoplasms

[<sup>18</sup>F]tetrafluoroborate (TFB) has been introduced as the <sup>18</sup>F-labeled PET imaging probe for the human sodium iodide symporter (NIS). Noninvasive NIS imaging using [<sup>18</sup>F]TFB has received much interest in recent years for evaluating various NIS-expressing tumors. Cancers are a global concern with enormous implications; therefore, improving diagnostic methods for accurate detection of cancer is extremely important. Our aim was to investigate the PET imaging capabilities of [<sup>18</sup>F]TFB in NIS-transfected lung cell line A549 and endogenous NIS-expressing tumor cells, such as thyroid cancer K1 and gastric cancer MKN45, and broaden its application in the medical field. Western blot and flow cytometry were used to assess the NIS expression level. Radioactivity counts of [<sup>18</sup>F]TFB, <i>in vitro</i>, in the three tumor cells were substantially higher than those in the KI inhibition group in the uptake experiment. <i>In vivo</i> PET imaging clearly delineated the three tumors based on the specific accumulation of [<sup>18</sup>F]TFB in a mouse model. <i>Ex vivo</i> biodistribution investigation showed high [<sup>18</sup>F]TFB absorption in the tumor location, which was consistent with the PET imaging results. These results support the use of NIS-transfected lung cell line A549 and NIS-expressing tumor cells MKN45 and K1, to investigate probing capabilities of [<sup>18</sup>F]TFB. We also demonstrate, for the first time, the feasibility of [<sup>18</sup>F]TFB in diagnosing stomach cancer. In conclusion, this study illustrates the promising future of [<sup>18</sup>F]TFB for tumor diagnosis and NIS reporter imaging.

Mengda Niu

Jingjing Qin

Liang Wang

Yujia He

Chuanhuizi Tian

Yanyan Chen

Pufeng Huang

Zhiping Peng

Evaluation of [<sup>18</sup>F]tetrafluoroborate as a Potential PET Imaging Agent in a Sodium Iodide Symporter-Transfected Cell Line A549 and Endogenous NIS-Expressing Cell Lines MKN45 and K1

<i>Objectives</i>. In patients with prostate cancer (PC) receiving prostate-specific membrane antigen- (PSMA-) targeted radioligand therapy (RLT), higher baseline standardized uptake values (SUVs) are linked to improved outcome. Thus, readers deciding on RLT must have certainty on the repeatability of PSMA uptake metrics. As such, we aimed to evaluate the test-retest repeatability of lesion uptake in a large cohort of patients imaged with <sup>18</sup>F-DCFPyL. <i>Methods</i>. In this prospective, IRB-approved trial (<a target="_blank" href="https://clinicaltrials.gov/ct2/show/NCT03793543">NCT03793543</a>), 21 patients with history of histologically proven PC underwent two <sup>18</sup>F-DCFPyL PET/CTs within 7 days (mean 3.7, range 1 to 7 days). Lesions in the bone, lymph nodes (LN), and other organs were manually segmented on both scans, and uptake parameters were assessed (maximum (SUV<sub>max</sub>) and mean (SUV<sub>mean</sub>) SUVs), PSMA-tumor volume (PSMA-TV), and total lesion PSMA (TL-PSMA, defined as <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="75.573pt" style="vertical-align:-3.272861pt" id="M1" height="12.0262pt" version="1.1" viewBox="-0.0498162 -8.75334 75.573 12.0262"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-81" d="M46 650V622C120 617 128 613 128 525V125C128 42 120 34 40 28V0H311V28C221 34 212 39 212 124V281L286 262C297 261 316 261 331 263C429 275 526 338 526 468C526 533 501 579 462 609C422 638 364 650 293 650H46ZM212 559C212 588 215 600 223 606C230 613 251 618 279 618C361 618 430 572 430 464C430 337 350 302 285 302C252 302 225 309 212 314V559Z"/></g><g transform="matrix(.013,0,0,-0.013,7.319,0)"><path id="g190-84" d="M409 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407 475 389 446 366C425 418 382 449 334 449C303 449 279 437 253 421C222 403 201 385 180 371V452C135 432 85 419 41 411V388C99 379 102 374 102 310V103C102 38 93 32 27 26V0H238V26C189 32 180 38 180 103V338C210 363 250 390 289 390C351 390 377 348 377 275V103C377 37 368 32 306 26V0H520V26C465 32 456 38 456 101V296C456 314 455 326 453 338C491 369 529 390 565 390C628 390 653 345 653 274V107C653 36 642 32 583 26V0H797Z"/></g><g transform="matrix(.0091,0,0,-0.0091,110.622,3.132)"><path id="g190-102" d="M380 106C343 72 306 56 265 56C195 56 116 112 115 248C235 252 361 262 377 265C396 269 400 277 400 297C400 374 333 449 250 449H249C198 449 144 421 103 376S37 269 37 201C37 88 109 -12 232 -12C263 -12 332 6 395 84L380 106ZM225 412C281 412 315 364 314 312C314 297 308 292 290 292C232 290 176 289 120 289C135 370 180 412 225 412Z"/></g><g transform="matrix(.0091,0,0,-0.0091,114.545,3.132)"><path id="g190-98" d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z"/></g><g transform="matrix(.0091,0,0,-0.0091,118.457,3.132)"><path id="g190-111" d="M524 0V26C466 32 460 36 460 104V297C460 393 411 449 331 449C302 449 276 437 248 419C223 402 201 387 181 372V451C137 432 90 420 42 411V388C96 378 102 374 102 310V104C102 38 97 33 29 26V0H246V26C187 32 181 36 181 104V339C211 365 250 390 290 390C357 390 381 345 381 276V109C381 40 374 32 315 26V0H524Z"/></g></svg>))</span></span>. Repeatability was determined using Pearson’s correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. <i>Results</i>. In total, 230 pairs of lesions (177 bone, 38 LN, and 15 other) were delineated, demonstrating a wide range of SUV<sub>max</sub> (1.5–80.5) and SUV<sub>mean</sub> (1.4–24.8). Including all sites of suspected disease, SUVs had a strong interscan correlation (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="24.361pt" style="vertical-align:-1.1198pt" id="M2" height="12.7112pt" version="1.1" viewBox="-0.0498162 -11.5914 24.361 12.7112"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-83" d="M610 18C585 26 567 34 540 68C517 97 499 128 476 171C452 215 425 276 413 304C496 332 570 394 570 494C570 555 545 595 509 619S419 650 364 650H139L133 622C216 615 219 612 203 527L129 132C112 40 105 36 23 28L17 0H279L285 28C199 34 194 40 211 132L239 284H284C320 284 334 275 351 236C374 182 394 140 420 93C459 23 495 -1 592 -8H600L610 18ZM480 485C480 424 449 372 403 342C374 323 338 316 293 316H245L291 562C296 589 301 601 311 608S337 618 358 618C432 618 480 575 480 485Z"/></g><g transform="matrix(.0091,0,0,-0.0091,8.151,-5.741)"><path id="g50-51" d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"/></g><g transform="matrix(.013,0,0,-0.013,16.73,0)"><path id="g117-94" d="M531 285V335L57 550V494L473 310L57 127V71L531 285ZM531 -40V10H57V-40H531Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.924pt" style="vertical-align:-1.1198pt" height="12.7112pt" version="1.1" viewBox="27.942183800000002 -11.5914 21.924 12.7112"><g transform="matrix(.013,0,0,-0.013,27.992,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,34.232,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,37.196,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g><g transform="matrix(.013,0,0,-0.013,43.438,0)"><use xlink:href="#g113-58"/></g></svg>),</span></span> with high repeatability for SUV<sub>mean</sub> and SUV<sub>max</sub> (wCOV, 7.3% and 12.1%, respectively). High SUVs showed significantly improved wCOV relative to lower SUVs (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M3" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="34.445pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 34.445 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.845,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>),</span></span> indicating that high SUVs are more repeatable, relative to the magnitude of the underlying SUV. Repeatability for PSMA-TV and TL-PSMA, however, was low (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="47.669pt" style="vertical-align:-1.11981pt" id="M4" height="9.87315pt" version="1.1" viewBox="-0.0498162 -8.75334 47.669 9.87315"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-120" d="M696 437H516V411C580 402 587 397 574 345C555 271 527 183 505 114H503C461 222 420 328 383 432H357C315 316 278 214 241 118H239C214 195 189 274 165 350C151 396 156 402 216 411V437H9V411C57 405 65 398 83 346C125 226 162 108 199 -11H227C267 100 308 199 346 300C387 195 428 97 468 -11H497C542 124 587 257 617 337C637 392 646 404 696 411V437Z"/></g><g transform="matrix(.013,0,0,-0.013,8.905,0)"><path id="g190-68" d="M614 175C564 76 510 21 408 21C256 21 146 149 146 336C146 488 235 629 402 629C510 629 570 586 597 480L626 488C620 541 614 582 606 638C578 643 510 665 429 665C206 665 44 527 44 316C44 157 153 -15 402 -15C474 -15 558 5 586 11C604 45 629 119 643 165L614 175Z"/></g><g transform="matrix(.013,0,0,-0.013,17.641,0)"><path id="g190-80" d="M381 665C170 665 44 498 44 318C44 125 188 -15 369 -15C552 -15 703 117 703 333C703 534 550 665 381 665ZM359 629C491 629 601 517 601 306C601 114 502 21 390 21C249 21 146 158 146 346S248 629 359 629Z"/></g><g transform="matrix(.013,0,0,-0.013,27.13,0)"><use xlink:href="#g190-87"/></g><g transform="matrix(.013,0,0,-0.013,40.038,0)"><use xlink:href="#g117-94"/></g></svg><span class="irelop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.893pt" style="vertical-align:-1.11981pt" height="9.87315pt" version="1.1" viewBox="51.2511838 -8.75334 21.893 9.87315"><g transform="matrix(.013,0,0,-0.013,51.301,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.013,0,0,-0.013,57.541,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.013,0,0,-0.013,63.781,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,66.745,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg></span>%). Across all metrics for LN and bone lesions, interscan correlation was again strong (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="24.361pt" style="vertical-align:-1.1198pt" id="M5" height="12.7112pt" version="1.1" viewBox="-0.0498162 -11.5914 24.361 12.7112"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-83"/></g><g transform="matrix(.0091,0,0,-0.0091,8.151,-5.741)"><use xlink:href="#g50-51"/></g><g transform="matrix(.013,0,0,-0.013,16.73,0)"><use xlink:href="#g117-94"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.924pt" style="vertical-align:-1.1198pt" height="12.7112pt" version="1.1" viewBox="27.942183800000002 -11.5914 21.924 12.7112"><g transform="matrix(.013,0,0,-0.013,27.992,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,34.232,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,37.196,0)"><use xlink:href="#g113-58"/></g><g transform="matrix(.013,0,0,-0.013,43.438,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g></svg>).</span></span> Moreover, LN-based SUV<sub>mean</sub> also achieved the best wCOV (3.8%), which was significantly reduced when compared to osseous lesions (7.8%, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M6" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="34.445pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 34.445 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.845,0)"><use xlink:href="#g113-50"/></g></svg>).</span></span> This was also noted for SUV<sub>max</sub> (wCOV, LN 8.8% vs. bone 12.0%, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M7" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-52"/></g></svg>).</span></span> On a compartment-based level, wCOVs for volumetric features were ≥22.8%, demonstrating no significant differences between LN and bone lesions (PSMA-TV, <i>P</i> =0.63; TL-PSMA, <i>P</i> =0.9). Findings on an entire tumor burden level were also corroborated in a hottest lesion analysis investigating the SUV<sub>max</sub> of the most intense lesion per patient (<span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M8" height="11.7978pt" version="1.1" viewBox="-0.0498162 -11.5914 13.2276 11.7978" width="13.2276pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-83"/></g><g transform="matrix(.0091,0,0,-0.0091,8.151,-5.741)"><use xlink:href="#g50-51"/></g></svg>,</span> 0.99; wCOV, 11.2%). <i>Conclusion</i>. In this prospective test-retest setting, SUV parameters demonstrated high repeatability, in particular in LNs, while volumetric parameters demonstrated low repeatability. Further, the large number of lesions and wide distribution of SUVs included in this analysis allowed for the demonstration of a dependence of repeatability on SUV, with higher SUVs having more robust repeatability.

Rudolf A. Werner

Bilêl Habacha

Susanne Lütje

Lena Bundschuh

Takahiro Higuchi

Philipp Hartrampf

Sebastian E. Serfling

Thorsten Derlin

Constantin Lapa

Andreas K. Buck

Markus Essler

Kenneth J. Pienta

Mario A. Eisenberger

Mark C. Markowski

Laura Shinehouse

Rehab AbdAllah

Ali Salavati

Martin A. Lodge

Martin G. Pomper

Michael A. Gorin

Ralph A. Bundschuh

Steven P. Rowe

High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with <sup>18</sup>F-DCFPyL

Immune therapy of T-cell lymphoma requires assessment of tumor-expressed programmed cell death protein-1 (PD-1). Herein, we developed an immuno-PET technique that quantitatively images and monitors regulation of PD-1 expression on T-cell lymphomas. <i>Methods</i>. Anti-PD-1 IgG underwent sulfhydryl moiety-specific conjugation with maleimide-deferoxamine and <sup>89</sup>Zr labeling. Binding assays and Western blotting were performed in EL4 murine T-cell lymphoma cells. In vivo pharmacokinetics, biodistribution, and PET were performed in mice. <i>Results</i>. <sup>89</sup>Zr-PD-1 IgG binding to EL4 cells was completely blocked by cold antibodies, confirming excellent target specificity. Following intravenous injection into mice, <sup>89</sup>Zr-PD-1 IgG showed biexponential blood clearance and relatively low normal organ uptake after five days. PET/CT and biodistribution demonstrated high EL4 tumor uptake that was suppressed by cold antibodies. In EL4 cells, phorbol 12-myristate 13-acetate (PMA) increased <sup>89</sup>Zr-PD-1 IgG binding (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="38.461pt" style="vertical-align:-0.3499298pt" id="M1" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 38.461 8.69875"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 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width="21.997pt" style="vertical-align:-0.3499298pt" height="8.69875pt" version="1.1" viewBox="41.317183799999995 -8.34882 21.997 8.69875"><g transform="matrix(.013,0,0,-0.013,41.367,0)"><use xlink:href="#g113-52"/></g><g transform="matrix(.013,0,0,-0.013,47.607,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,53.847,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,56.811,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g></svg></span>%) and dose-dependent augmentation of PD-1 expression (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="32.221pt" style="vertical-align:-0.3499298pt" id="M2" height="9.65783pt" version="1.1" viewBox="-0.0498162 -9.3079 32.221 9.65783"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-54"/></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,15.444,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g><g transform="matrix(.013,0,0,-0.013,24.59,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="49.682pt" style="vertical-align:-0.3499298pt" height="9.65783pt" version="1.1" viewBox="35.076183799999995 -9.3079 49.682 9.65783"><g transform="matrix(.013,0,0,-0.013,35.126,0)"><use xlink:href="#g113-52"/></g><g transform="matrix(.013,0,0,-0.013,41.366,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,44.33,0)"><use xlink:href="#g113-57"/></g><g transform="matrix(.013,0,0,-0.013,53.476,0)"><path id="g117-33" d="M535 230V280H52V230H535Z"/></g><g transform="matrix(.013,0,0,-0.013,64.012,0)"><path id="g190-103" d="M54 437L27 408L31 397H101V103C101 37 94 32 30 26V0H266V25C187 33 180 36 180 110V397H288C299 404 304 428 298 437H180V477C179 562 190 610 203 630C214 647 230 659 256 659C289 659 318 641 337 622C346 612 355 612 364 619C374 627 380 635 383 643C388 655 387 667 378 678C362 697 333 710 299 712C260 707 225 689 189 659C135 613 119 563 112 541S101 490 101 458V437H54Z"/></g><g transform="matrix(.013,0,0,-0.013,67.743,0)"><path id="g190-112" d="M257 449C165 449 37 374 37 209C37 98 119 -12 256 -12C355 -12 473 65 473 226C473 349 381 449 257 449ZM244 416C333 416 380 320 380 204C380 67 329 21 267 21C184 21 130 115 130 241C130 354 184 416 244 416Z"/></g><g transform="matrix(.013,0,0,-0.013,74.282,0)"><path id="g190-109" d="M238 0V26C174 32 166 38 166 104V712C132 700 70 683 18 677V653C81 647 87 645 87 577V104C87 38 78 32 15 26V0H238Z"/></g><g transform="matrix(.013,0,0,-0.013,77.571,0)"><path id="g190-101" d="M517 51L485 54C448 58 441 63 441 115V712C404 700 337 684 285 678V653C357 648 362 645 362 580V437C339 446 309 449 295 449C159 449 38 340 38 201C38 61 143 -12 223 -12C234 -12 261 -6 301 17L362 53V-12C420 9 495 22 517 26V51ZM362 85C338 67 301 51 266 51C201 51 128 109 128 228C128 373 212 411 259 411C296 411 338 395 362 360V85Z"/></g></svg></span> of controls by 200 ng/ml). FACS showed strong PD-1 expression on all EL4 cells and positive but weaker expression on <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="32.221pt" style="vertical-align:-0.3499298pt" id="M3" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 32.221 8.69875"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,15.444,0)"><use xlink:href="#g113-55"/></g><g transform="matrix(.013,0,0,-0.013,24.59,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="15.711pt" style="vertical-align:-0.3499298pt" height="8.69875pt" version="1.1" viewBox="35.076183799999995 -8.34882 15.711 8.69875"><g transform="matrix(.013,0,0,-0.013,35.126,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.013,0,0,-0.013,41.366,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,44.33,0)"><use xlink:href="#g113-50"/></g></svg></span>% of the mouse spleen lymphocytes. PMA stimulation led to <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="25.983pt" style="vertical-align:-0.3499298pt" id="M4" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 25.983 8.69875"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,9.204,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g><g transform="matrix(.013,0,0,-0.013,18.352,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="15.686pt" style="vertical-align:-0.3499298pt" height="8.69875pt" version="1.1" viewBox="28.838183800000003 -8.34882 15.686 8.69875"><g transform="matrix(.013,0,0,-0.013,28.888,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,35.128,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,38.092,0)"><use xlink:href="#g113-52"/></g></svg>-</span></span>fold increase in the proportion of the strongest PD-1 expressing EL4 cells but failed to influence that of PD-1+ mouse lymphocytes. In mice, PMA treatment increased <sup>89</sup>Zr-PD-1 IgG uptake in EL4 lymphomas from <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="25.981pt" style="vertical-align:-0.3499298pt" id="M5" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 25.981 8.69875"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-55"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,9.204,0)"><use xlink:href="#g113-55"/></g><g transform="matrix(.013,0,0,-0.013,18.35,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="15.688pt" style="vertical-align:-0.3499298pt" height="8.69875pt" version="1.1" viewBox="28.8361838 -8.34882 15.688 8.69875"><g transform="matrix(.013,0,0,-0.013,28.886,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,35.126,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,38.09,0)"><use xlink:href="#g113-55"/></g></svg></span> to <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="32.222pt" style="vertical-align:-0.3499298pt" id="M6" height="8.69875pt" version="1.1" viewBox="-0.0498162 -8.34882 32.222 8.69875"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-52"/></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,15.444,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 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xlink:href="#g113-50"/></g></svg>),</span></span> and tumor uptake closely correlated with PD-1 level (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="16.751pt" style="vertical-align:-0.2063904pt" id="M8" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 16.751 8.55521"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-115" d="M393 379C402 394 400 411 393 422C384 437 365 448 348 448C301 448 237 372 186 285H182L193 335C210 408 205 448 178 448C150 448 80 402 29 344L45 321C80 355 114 373 122 373C128 373 130 365 124 330C106 228 76 98 50 -5L57 -12C82 -5 112 3 132 6L172 203C196 256 234 304 254 329C275 355 293 367 306 367C318 367 330 360 342 348C347 343 355 343 365 350S386 367 393 379Z"/></g><g transform="matrix(.013,0,0,-0.013,9.12,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.175pt" style="vertical-align:-0.2063904pt" height="8.55521pt" version="1.1" viewBox="20.3331838 -8.34882 28.175 8.55521"><g transform="matrix(.013,0,0,-0.013,20.383,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,26.623,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,29.587,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.013,0,0,-0.013,35.829,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.013,0,0,-0.013,42.071,0)"><use xlink:href="#g113-50"/></g></svg>,</span></span> <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M9" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-50"/></g></svg>).</span></span> On immunohistochemistry of tumor sections, infiltrating CD8<i>α</i>+ T lymphocytes constituted a small fraction of tumor cells. The entire tumor section showed strong PD-1 staining that was even stronger for PMA-treated mice. Investigation of involved signaling revealed that PMA increased EL4 cell and tumor HIF-1<i>α</i> accumulation and NF<i>κ</i>B and JNK activation. <i>Conclusion</i>. <sup>89</sup>Zr-PD-1 IgG offered high-contrast PET imaging of tumor PD-1 in mice. This was found to mostly represent binding to EL4 tumor cells, although infiltrating T lymphocytes may also have contributed. PD-1 expression on T-cell lymphomas was upregulated by PMA stimulation, and this was reliably monitored by <sup>89</sup>Zr-PD-1 IgG PET. This technique may thus be useful for understanding the mechanisms of PD-1 regulation in lymphomas of living subjects.

Kyung-Ho Jung

Jin Hee Lee

Mina Kim

Young Seok Cho

Kyung-Han Lee

<sup>89</sup>Zr Immuno-PET Imaging of Tumor PD-1 Reveals That PMA Upregulates Lymphoma PD-1 through NF<i>κ</i>B and JNK Signaling

Location and extent of necrosis are valuable information in the management of myocardial infarction (MI). <i>Methods</i>. We investigated 2-deoxy-2-<sup>18</sup>F-fluoro glucaric acid (FGA), a novel infarct-avid agent, for positron emission tomography (PET) of MI. We synthesized FGA from commercially available <sup>18</sup>F-fluoro-2-deoxy-2-D-glucose (FDG). MI was induced in mice by permanently occluding the left anterior descending coronary artery. Biodistribution of FGA was assessed 1 h after FGA injection (11 MBq). PET/CT was conducted 1 h, 6 h, 1 d, 3 d, and 4 d after MI. Subcellular compartment of FGA accumulation in necrosis was studied by tracing the uptake of biotin-labeled glucaric acid with streptavidin-HRP in H<sub>2</sub>O<sub>2</sub>-treated H9c2 cardiomyoblasts. Streptavidin-reactive protein bands were identified by LC-MS/MS. <i>Results</i>. We obtained a quantitative yield of FGA from FDG within 7 min (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="119.798pt" style="vertical-align:-3.403299pt" id="M1" height="12.7112pt" version="1.1" viewBox="-0.0498162 -9.3079 119.798 12.7112"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-115" d="M181 342V451C133 431 89 419 40 411V388C98 381 102 377 102 311V104C102 38 95 32 33 26V0H263V26C186 32 181 38 181 104V287C203 343 235 372 261 372C277 372 289 366 304 352C310 346 318 345 330 350C349 359 362 379 362 399C362 422 338 449 304 449C256 449 213 393 183 342H181Z"/></g><g transform="matrix(.013,0,0,-0.013,4.823,0)"><path id="g190-98" d="M433 39L423 65C413 59 399 54 387 54C370 54 352 69 352 114V299C352 352 342 392 307 422C285 440 255 449 225 449C168 437 102 399 75 379C56 365 44 353 44 339C44 315 69 296 87 296C101 296 111 303 116 319C124 349 133 371 145 385C156 397 171 404 190 404C241 404 275 364 275 291V274C253 256 180 229 120 209C65 190 39 159 39 110C39 47 88 -12 159 -12C189 -12 237 25 277 52C282 35 288 21 301 8C312 -3 333 -12 348 -12L433 39ZM275 84C256 65 221 48 195 48C164 48 124 73 124 124C124 161 146 180 185 198C206 208 254 229 275 240V84Z"/></g><g transform="matrix(.013,0,0,-0.013,10.53,0)"><path id="g190-101" d="M517 51L485 54C448 58 441 63 441 115V712C404 700 337 684 285 678V653C357 648 362 645 362 580V437C339 446 309 449 295 449C159 449 38 340 38 201C38 61 143 -12 223 -12C234 -12 261 -6 301 17L362 53V-12C420 9 495 22 517 26V51ZM362 85C338 67 301 51 266 51C201 51 128 109 128 228C128 373 212 411 259 411C296 411 338 395 362 360V85Z"/></g><g transform="matrix(.013,0,0,-0.013,17.394,0)"><path id="g190-106" d="M135 536C164 536 186 560 186 587C186 617 164 639 136 639C109 639 85 617 85 587C85 560 109 536 135 536ZM252 0V26C188 32 181 38 181 106V451C138 433 90 420 39 412V388C99 379 102 374 102 312V106C102 38 95 32 32 26V0H252Z"/></g><g transform="matrix(.013,0,0,-0.013,20.878,0)"><path 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transform="matrix(.013,0,0,-0.013,39.936,0)"><path id="g190-102" d="M380 106C343 72 306 56 265 56C195 56 116 112 115 248C235 252 361 262 377 265C396 269 400 277 400 297C400 374 333 449 250 449H249C198 449 144 421 103 376S37 269 37 201C37 88 109 -12 232 -12C263 -12 332 6 395 84L380 106ZM225 412C281 412 315 364 314 312C314 297 308 292 290 292C232 290 176 289 120 289C135 370 180 412 225 412Z"/></g><g transform="matrix(.013,0,0,-0.013,45.461,0)"><path id="g190-110" d="M797 0V26C739 32 732 36 732 103V296C732 394 682 449 605 449C576 449 550 437 529 423C504 407 475 389 446 366C425 418 382 449 334 449C303 449 279 437 253 421C222 403 201 385 180 371V452C135 432 85 419 41 411V388C99 379 102 374 102 310V103C102 38 93 32 27 26V0H238V26C189 32 180 38 180 103V338C210 363 250 390 289 390C351 390 377 348 377 275V103C377 37 368 32 306 26V0H520V26C465 32 456 38 456 101V296C456 314 455 326 453 338C491 369 529 390 565 390C628 390 653 345 653 274V107C653 36 642 32 583 26V0H797Z"/></g><g 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191 -49 173 -84C149 -128 130 -153 98 -172C81 -184 73 -193 73 -209C73 -233 101 -257 129 -257C143 -257 156 -252 161 -232C175 -179 197 -122 264 38C333 203 364 286 390 339C417 395 425 403 478 411V437Z"/></g><g transform="matrix(.013,0,0,-0.013,112.167,0)"><path id="g117-92" d="M512 230V281L75 514V456L453 256V254L75 55V-3L512 230Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="22.52pt" style="vertical-align:-3.403299pt" height="12.7112pt" version="1.1" viewBox="123.38018380000001 -9.3079 22.52 12.7112"><g transform="matrix(.013,0,0,-0.013,123.43,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g><g transform="matrix(.013,0,0,-0.013,129.672,0)"><use xlink:href="#g113-58"/></g><g transform="matrix(.013,0,0,-0.013,135.913,0)"><path id="g121-35" d="M594 629L561 652L159 -9L190 -32L594 629ZM194 635C92 635 49 534 49 453C49 374 92 272 193 272C295 272 338 374 338 454S295 635 194 635ZM193 605C257 605 265 504 265 453C265 405 257 302 194 302C133 302 122 403 122 454S133 605 193 605ZM567 351C465 351 421 250 421 169C421 90 465 -12 566 -12S710 90 710 170S667 351 567 351ZM566 322C628 322 637 221 637 169C637 121 628 18 567 18S494 119 494 170C494 223 506 322 566 322Z"/></g></svg>).</span></span> Cardiac uptake of FGA was significantly higher in MI mice than that in control mice. Imaging after 1 h of FGA injection delineated MI for 3 days after MI induction, with negligible background signal from surrounding tissues. Myocardial injury was verified by tetrazolium staining and plasma troponin (47.63 pg/mL control versus 311.77 pg/mL MI). In necrotic H9c2 myoblasts, biotinylated glucaric acid accumulated in nuclear fraction. LC-MS/MS primarily identified fibronectin in necrotic cells as a putative high fidelity target of glucaric acid. <i>Conclusion</i>. FGA/PET detects infarct early after onset of MI and FGA accumulation in infarct persists for 3 days. Its retention in necrotic cells appears to be a result of interaction with fibronectin that is known to accumulate in injured cardiac tissue.

Vibhudutta Awasthi

Hariprasad Gali

Andria F. Hedrick

Huining Da

Venkateswararao Eeda

Diwakar Jain

Positron Emission Tomography (PET) with <sup>18</sup>F-FGA for Diagnosis of Myocardial Infarction in a Coronary Artery Ligation Model

We developed an immuno-PET technique that monitors modulation of tumor CD133 expression, which is required for the success of CD133-targeted therapies. <i>Methods</i>. Anti-CD133 antibodies were subjected to sulfhydryl moiety-specific <sup>89</sup>Zr conjugation. <sup>89</sup>Zr-CD133 IgG was evaluated for specific activity and radiolabel stability. Colon cancer cells underwent binding assays and Western blotting. Biodistribution and PET studies were performed in mice. <i>Results</i>. <sup>89</sup>Zr-CD133 IgG showed excellent target specificity with <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="32.224pt" style="vertical-align:-0.4673595pt" id="M1" height="8.85534pt" version="1.1" viewBox="-0.0498162 -8.38798 32.224 8.85534"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g><g transform="matrix(.013,0,0,-0.013,6.241,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g><g transform="matrix(.013,0,0,-0.013,12.483,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.013,0,0,-0.013,15.447,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.013,0,0,-0.013,24.593,0)"><path id="g117-37" d="M535 290V340H323V533H265V340H52V290H265V84H323V290H535ZM535 -22V28H52V-22H535Z"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="25.573pt" style="vertical-align:-0.4673595pt" height="8.85534pt" version="1.1" viewBox="35.079183799999996 -8.38798 25.573 8.85534"><g transform="matrix(.013,0,0,-0.013,35.129,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.013,0,0,-0.013,41.369,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,44.333,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.013,0,0,-0.013,50.576,0)"><path id="g121-35" d="M594 629L561 652L159 -9L190 -32L594 629ZM194 635C92 635 49 534 49 453C49 374 92 272 193 272C295 272 338 374 338 454S295 635 194 635ZM193 605C257 605 265 504 265 453C265 405 257 302 194 302C133 302 122 403 122 454S133 605 193 605ZM567 351C465 351 421 250 421 169C421 90 465 -12 566 -12S710 90 710 170S667 351 567 351ZM566 322C628 322 637 221 637 169C637 121 628 18 567 18S494 119 494 170C494 223 506 322 566 322Z"/></g></svg></span> blocking of HT29 cell binding by an excess antibody. Intravenous <sup>89</sup>Zr-CD133 IgG followed biexponential blood clearance and showed CD133-specific uptake in HT29 tumors. <sup>89</sup>Zr-CD133 IgG PET/CT and biodistribution studies confirmed high HT29 tumor uptake with lower activities in the blood and normal organs. In HT29 cells, celecoxib dose-dependently decreased CD133 expression and <sup>89</sup>Zr-CD133 IgG binding that reached <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="32.223pt" style="vertical-align:-0.4673595pt" id="M2" height="8.85534pt" version="1.1" viewBox="-0.0498162 -8.38798 32.223 8.85534"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-58"/></g><g transform="matrix(.013,0,0,-0.013,12.481,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,15.445,0)"><use xlink:href="#g113-58"/></g><g transform="matrix(.013,0,0,-0.013,24.592,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="25.574pt" style="vertical-align:-0.4673595pt" height="8.85534pt" version="1.1" viewBox="35.0781838 -8.38798 25.574 8.85534"><g transform="matrix(.013,0,0,-0.013,35.128,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,41.368,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,44.332,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,50.572,0)"><use xlink:href="#g121-35"/></g></svg></span> (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M3" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 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xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M5" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-50"/></g></svg>)</span></span> of baseline levels by 50 <i>μ</i>M, respectively. Celecoxib treatment of mice significantly suppressed tumor CD133 expression to <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="32.223pt" style="vertical-align:-0.4673595pt" id="M6" height="8.85534pt" version="1.1" viewBox="-0.0498162 -8.38798 32.223 8.85534"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.013,0,0,-0.013,12.482,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,15.446,0)"><use xlink:href="#g113-54"/></g><g transform="matrix(.013,0,0,-0.013,24.592,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="25.573pt" style="vertical-align:-0.4673595pt" height="8.85534pt" version="1.1" viewBox="35.079183799999996 -8.38798 25.573 8.85534"><g transform="matrix(.013,0,0,-0.013,35.129,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.013,0,0,-0.013,41.371,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,44.335,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g><g transform="matrix(.013,0,0,-0.013,50.575,0)"><use xlink:href="#g121-35"/></g></svg></span> of controls (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M7" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.182pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 28.182 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.605,0)"><use xlink:href="#g113-54"/></g></svg>)</span></span> and reduced tumor <sup>89</sup>Zr-CD133 IgG uptake from <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="32.221pt" style="vertical-align:-0.4673595pt" id="M8" height="8.85534pt" version="1.1" viewBox="-0.0498162 -8.38798 32.221 8.85534"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-54"/></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,15.444,0)"><use xlink:href="#g113-54"/></g><g transform="matrix(.013,0,0,-0.013,24.59,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="25.576pt" style="vertical-align:-0.4673595pt" height="8.85534pt" version="1.1" viewBox="35.076183799999995 -8.38798 25.576 8.85534"><g transform="matrix(.013,0,0,-0.013,35.126,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,41.366,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,44.33,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g><g transform="matrix(.013,0,0,-0.013,50.571,0)"><use xlink:href="#g121-35"/></g></svg></span> at baseline to <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="32.221pt" style="vertical-align:-3.40337pt" id="M9" height="12.6917pt" version="1.1" viewBox="-0.0498162 -9.28833 32.221 12.6917"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,15.444,0)"><use xlink:href="#g113-52"/></g><g transform="matrix(.013,0,0,-0.013,24.59,0)"><use xlink:href="#g117-37"/></g></svg><span class="ibiop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="44.669pt" style="vertical-align:-3.40337pt" height="12.6917pt" version="1.1" viewBox="35.076183799999995 -9.28833 44.669 12.6917"><g transform="matrix(.013,0,0,-0.013,35.126,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.013,0,0,-0.013,41.366,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,44.33,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,50.57,0)"><use xlink:href="#g121-35"/></g><g transform="matrix(.013,0,0,-0.013,60.398,0)"><path id="g190-74" d="M303 0V28C221 34 213 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283C51 215 94 168 139 149C123 129 91 103 51 88C50 78 53 60 62 46C75 25 100 2 136 -9C112 -28 73 -59 53 -79C38 -94 29 -113 29 -135C30 -192 91 -257 203 -257C336 -257 452 -160 452 -59C452 39 371 59 309 59C275 59 240 58 203 58C158 58 140 77 140 96C140 110 157 129 170 138C186 135 205 133 221 133C306 133 396 185 396 293C396 328 384 360 366 381L423 378C439 387 459 413 468 429L463 437ZM219 418C277 418 314 362 314 284C314 205 275 166 231 165C176 165 137 221 137 299C137 376 177 418 219 418ZM241 -11C285 -11 314 -14 339 -24C367 -36 384 -61 384 -95C384 -157 335 -206 240 -206C166 -206 108 -165 108 -110C108 -82 128 -54 154 -32C172 -17 195 -11 241 -11Z"/></g></svg></span> (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="19.289pt" style="vertical-align:-0.6370001pt" id="M10" height="9.2729pt" version="1.1" viewBox="-0.0498162 -8.6359 19.289 9.2729"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><use xlink:href="#g117-91"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="21.918pt" style="vertical-align:-0.6370001pt" height="9.2729pt" version="1.1" viewBox="22.8711838 -8.6359 21.918 9.2729"><g transform="matrix(.013,0,0,-0.013,22.921,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><use xlink:href="#g113-50"/></g></svg>).</span></span> Celecoxib-induced CD133 reduction in HT29 cells and tumors was associated with substantial suppression of AKT activation. There were also reduced HIF-1<i>α</i> accumulation and I<i>κ</i>B<i>α</i>/NF<i>κ</i>B phosphorylation. <i>Conclusion</i>. <sup>89</sup>Zr-CD133 IgG PET provides high-contrast tumor imaging and monitors celecoxib treatment-induced modulation of tumor CD133 expression, which was found to occur through AKT inhibition. This technique may thus be useful for screening drugs that can effectively suppress colon cancer stem cells.

Eun Ji Lee

Celecoxib-Induced Modulation of Colon Cancer CD133 Expression Occurs through AKT Inhibition and Is Monitored by <sup>89</sup>Zr Immuno-PET

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<p><em>Molecular Imaging</em> is a peer-reviewed journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. <em>Molecular Imaging</em> covers all imaging modalities.</p>


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<p>Chief Editor Henry VanBrocklin is a Professor at the University of California, San Francisco, USA, and Director of its Radiopharmaceutical Research Program. His research interests include short-lived radioisotope production and the creation of fluorine-18 and carbon-11 labeling chemistry strategies</p>


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Molecular Imaging - Table of contents 2022

title

Molecular Imaging is a peer-reviewed journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. Molecular Imaging covers all imaging modalities.

Molecular Imaging

Table of Contents

Table of Contents: 2022

The Potential Prognostic Value of Dual-Imaging PET Parameters Based on ¹⁸F-FDG and ¹⁸F-OC for Neuroendocrine Neoplasms

Evaluation of [¹⁸F]tetrafluoroborate as a Potential PET Imaging Agent in a Sodium Iodide Symporter-Transfected Cell Line A549 and Endogenous NIS-Expressing Cell Lines MKN45 and K1

High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with ¹⁸F-DCFPyL

⁸⁹Zr Immuno-PET Imaging of Tumor PD-1 Reveals That PMA Upregulates Lymphoma PD-1 through NFκB and JNK Signaling

Positron Emission Tomography (PET) with ¹⁸F-FGA for Diagnosis of Myocardial Infarction in a Coronary Artery Ligation Model

Celecoxib-Induced Modulation of Colon Cancer CD133 Expression Occurs through AKT Inhibition and Is Monitored by ⁸⁹Zr Immuno-PET

Molecular Imaging

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Table of Contents: 2022

The Potential Prognostic Value of Dual-Imaging PET Parameters Based on 18F-FDG and 18F-OC for Neuroendocrine Neoplasms

Evaluation of [18F]tetrafluoroborate as a Potential PET Imaging Agent in a Sodium Iodide Symporter-Transfected Cell Line A549 and Endogenous NIS-Expressing Cell Lines MKN45 and K1

High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with 18F-DCFPyL

89Zr Immuno-PET Imaging of Tumor PD-1 Reveals That PMA Upregulates Lymphoma PD-1 through NFκB and JNK Signaling

Positron Emission Tomography (PET) with 18F-FGA for Diagnosis of Myocardial Infarction in a Coronary Artery Ligation Model

Celecoxib-Induced Modulation of Colon Cancer CD133 Expression Occurs through AKT Inhibition and Is Monitored by 89Zr Immuno-PET