Stem cell therapy has shown great clinical potential in oncology, injury, inflammation, and cardiovascular disease. However, due to the technical limitations of the in vivo visualization of transplanted stem cells, the therapeutic mechanisms and biosafety of stem cells in vivo are poorly defined, which limits the speed of clinical translation. The commonly used methods for the in vivo tracing of stem cells currently include optical imaging, magnetic resonance imaging (MRI), and nuclear medicine imaging. However, nuclear medicine imaging involves radioactive materials, MRI has low resolution at the cellular level, and optical imaging has poor tissue penetration in vivo. It is difficult for a single imaging method to simultaneously achieve the high penetration, high resolution, and noninvasiveness needed for in vivo imaging. However, multimodal imaging combines the advantages of different imaging modalities to determine the fate of stem cells in vivo in a multidimensional way. This review provides an overview of various multimodal imaging technologies and labeling methods commonly used for tracing stem cells, including optical imaging, MRI, and the combination of the two, while explaining the principles involved, comparing the advantages and disadvantages of different combination schemes, and discussing the challenges and prospects of human stem cell tracking techniques.

Jia Yang

Min Yan

Zhong Wang

Cong Zhang

Miao Guan

Zhenglong Sun

Optical and MRI Multimodal Tracing of Stem Cells In Vivo

<i>Objective</i>. In this study, we utilized gonadotropin-releasing hormone analogue-modified indocyanine green (GnRHa-ICG) to improve the accuracy of intraoperative recognition and resection of endometriotic lesions. <i>Methods</i>. Gonadotropin-releasing hormone receptor (GnRHR) expression was detected in endometriosis tissues and cell lines via immunohistochemistry and western blotting. The in vitro binding capacities of GnRHa, GnRHa-ICG, and ICG were determined using fluorescence microscopy and flow cytometry. In vivo imaging was performed in mouse models of endometriosis using a near-infrared fluorescence (NIRF) imaging system and fluorescence navigation system. The ex vivo binding capacity was determined using confocal fluorescence microscopy. <i>Results</i>. GnRHa-ICG exhibited a significantly stronger binding capacity to endometriotic cells and tissues than ICG. In mice with endometriosis, GnRHa-ICG specifically imaged endometriotic tissues (EMTs) after intraperitoneal administration, whereas ICG exhibited signals in the intestine. GnRHa-ICG showed the highest fluorescence signals in the EMTs at 2 h and a good signal-to-noise ratio at 48 h postadministration. Compared with traditional surgery under white light, targeted NIRF imaging-guided surgery completely resected endometriotic lesions with a sensitivity of 97.3% and specificity of 77.8%. No obvious toxicity was observed in routine blood tests, serum biochemicals, or histopathology in mice. <i>Conclusions</i>. GnRHa-ICG specifically recognized and localized endometriotic lesions and guided complete resection of lesions with high accuracy.

Jing Peng

Qiyu Liu

Tao Pu

Mingxing Zhang

Meng Zhang

Ming Du

Guiling Li

Xiaoyan Zhang

Congjian Xu

Targeted Imaging of Endometriosis and Image-Guided Resection of Lesions Using Gonadotropin-Releasing Hormone Analogue-Modified Indocyanine Green

[<sup>18</sup>F]SynVesT-1 is a PET radiopharmaceutical that binds to the synaptic vesicle protein 2A (SV2A) and serves as a biomarker of synaptic density with widespread clinical research applications in psychiatry and neurodegeneration. The initial goal of this study was to concurrently conduct PET imaging studies with [<sup>18</sup>F]SynVesT-1 at our laboratories. However, the data in the first two human PET studies had anomalous biodistribution despite the injected product meeting all specifications during the prerelease quality control protocols. Further investigation, including imaging in rats as well as proton and carbon 2D-NMR spectroscopic studies, led to the discovery that a derivative of the precursor had been received from the manufacturer. Hence, we report our investigation and the first-in-human study of [<sup>18</sup>F]SDM-4MP3, a structural variant of [<sup>18</sup>F]SynVesT-1, which does not have the requisite characteristics as a PET radiopharmaceutical for imaging SV2A in the central nervous system.

Kimberly L. Desmond

Anton Lindberg

Armando Garcia

Junchao Tong

Michael B. Harkness

Elena Dobrota

Kelly Smart

Carme Uribe

Jeffrey H. Meyer

Sylvain Houle

Antonio P. Strafella

Songye Li

Yiyun Huang

Neil Vasdev

First-in-Human PET Imaging of [<sup>18</sup>F]SDM-4MP3: A Cautionary Tale

Amyotrophic lateral sclerosis (ALS) is a disease leading to progressive motor degeneration and ultimately death. It is a complex disease that can take a significantly long time to be diagnosed, as other similar pathological conditions must be ruled out for a definite diagnosis of ALS. Noninvasive imaging of ALS has shed light on disease pathology and altered biochemistry in the ALS brain. Other than magnetic resonance imaging (MRI), two types of functional imaging, positron emission tomography (PET) and single photon emission computed tomography (SPECT), have provided valuable data about what happens in the brain of ALS patients compared to healthy controls. PET imaging has revealed a specific pattern of brain metabolism through [<sup>18</sup>F]FDG, while other radiotracers have uncovered neuroinflammation, changes in neuronal density, and protein aggregation. SPECT imaging has shown a general decrease in regional cerebral blood flow (rCBF) in ALS patients. This educational review summarizes the current state of ALS imaging with various PET and SPECT radiopharmaceuticals to better understand the pathophysiology of ALS.

Ayaan M. Jamali

Manasa Kethamreddy

Brian J. Burkett

John D. Port

Mukesh K. Pandey

PET and SPECT Imaging of ALS: An Educational Review

Synaptic density in the central nervous system can be measured <i>in vivo</i> using PET with [<sup>18</sup>F]SynVesT-1. While [<sup>18</sup>F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson’s disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [<sup>18</sup>F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [<sup>18</sup>F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential (<span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.27282pt" id="M1" height="11.7978pt" version="1.1" viewBox="-0.0498162 -8.52498 29.1171 11.7978" width="29.1171pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-67" d="M372 352C427 368 507 407 507 502C507 548 486 592 451 616C420 638 376 650 301 650H44V622C124 616 128 610 128 527V123C128 40 122 34 36 28V0H257C336 0 402 12 453 40C512 72 548 124 548 191C548 291 471 335 372 350V352ZM213 362V558C213 591 216 602 226 608C235 614 258 618 282 618C377 618 415 558 415 490C415 406 369 362 260 362H213ZM213 328H258C380 328 450 283 450 181C450 76 377 35 296 34C231 34 213 53 213 125V328Z"/></g><g transform="matrix(.013,0,0,-0.013,7.673,0)"><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(.0091,0,0,-0.0091,15.019,3.132)"><path id="g190-79" d="M719 650H483V622C553 619 576 606 581 560C585 532 588 487 588 394V148H585L167 650H20V622C67 618 88 610 109 585C127 562 129 557 129 484V264C129 173 126 124 123 93C118 44 92 31 35 28V0H272V28C204 32 181 44 176 95C173 124 170 172 170 264V515H172L598 -9H629V394C629 487 631 532 635 563C639 606 663 619 719 622V650Z"/></g><g transform="matrix(.0091,0,0,-0.0091,21.78,3.132)"><path id="g190-69" d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z"/></g></svg>)</span> using centrum semiovale (CS) as a reference region. The SRTM2 method was used with <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.181499pt" id="M2" height="14.8721pt" version="1.1" viewBox="-0.0498162 -11.6906 15.3399 14.8721" width="15.3399pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-108" d="M480 416C480 431 465 448 438 448C388 448 312 383 252 330C217 299 188 273 155 237H153L257 680C262 700 263 712 253 712C240 712 183 684 97 674L92 648L126 647C166 646 172 645 163 606L23 -6L29 -12C51 -5 77 2 107 8C115 62 130 128 142 180C153 193 179 220 204 241C231 170 259 106 288 54C317 0 336 -12 358 -12C381 -12 423 2 477 80L460 100C434 74 408 54 398 54C385 54 374 65 351 107C326 154 282 241 263 299C296 332 351 377 403 377C424 377 436 372 445 368C449 366 456 368 462 375C472 386 480 402 480 416Z"/></g><g transform="matrix(.0091,0,0,-0.0091,6.474,3.132)"><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(.0091,0,0,-0.0091,11.445,-5.996)"><path id="g50-31" d="M310 541L304 571C290 586 211 619 185 610L80 76L131 52L310 541Z"/></g></svg> fixed to either a sample average value (0.037 min<sup>-1</sup>) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="23.848pt" style="vertical-align:-3.42938pt" id="M3" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 23.848 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,7.71,0)"><path id="g113-116" d="M352 391C352 416 319 448 267 448C236 448 173 423 147 400C107 364 96 332 96 304C96 248 143 210 193 181C241 153 258 124 258 100C258 72 232 38 184 38C151 38 107 66 81 108C77 114 64 116 55 111C34 99 23 84 23 65C23 29 81 -12 134 -12C220 -12 325 61 325 141C325 184 297 215 234 256C194 282 161 309 161 346C161 380 188 401 217 401C255 401 279 380 301 353C308 344 313 341 325 347C341 355 352 371 352 391Z"/></g><g transform="matrix(.013,0,0,-0.013,16.217,0)"><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="21.939pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="27.430183800000002 -8.34882 21.939 11.7782"><g transform="matrix(.013,0,0,-0.013,27.48,0)"><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 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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)"><use xlink:href="#g50-51"/></g><g transform="matrix(.013,0,0,-0.013,13.098,0)"><path id="g190-116" d="M319 325C317 349 306 409 297 431C277 440 250 449 209 449C117 449 57 389 57 319C57 243 122 209 182 182C232 159 261 135 261 91C261 48 227 21 190 21C130 21 85 79 68 145L41 140C41 104 51 36 58 22C75 7 121 -12 172 -12C252 -12 337 35 337 126C337 195 286 231 210 262C166 281 126 304 126 348C126 388 152 417 191 417C240 417 274 378 294 318L319 325Z"/></g><g transform="matrix(.013,0,0,-0.013,21.518,0)"><use xlink:href="#g117-92"/></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:-0.6370001pt" height="12.2284pt" version="1.1" viewBox="32.7311838 -11.5914 21.924 12.2284"><g transform="matrix(.013,0,0,-0.013,32.781,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,39.021,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,41.985,0)"><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,-0.013,48.226,0)"><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 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version="1.1" viewBox="35.3311838 -9.3079 22.52 9.9449"><g transform="matrix(.013,0,0,-0.013,35.381,0)"><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,-0.013,41.621,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,47.861,0)"><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> with no difference in bias between the control and PD groups. With SRTM2, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.27282pt" id="M7" height="11.7978pt" version="1.1" viewBox="-0.0498162 -8.52498 29.1171 11.7978" width="29.1171pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g190-67"/></g><g transform="matrix(.013,0,0,-0.013,7.673,0)"><use xlink:href="#g190-81"/></g><g transform="matrix(.0091,0,0,-0.0091,15.019,3.132)"><use xlink:href="#g190-79"/></g><g transform="matrix(.0091,0,0,-0.0091,21.78,3.132)"><use xlink:href="#g190-69"/></g></svg> estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="31.749pt" style="vertical-align:-0.6369991pt" id="M8" height="9.9449pt" version="1.1" viewBox="-0.0498162 -9.3079 31.749 9.9449"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g190-99"/></g><g transform="matrix(.013,0,0,-0.013,6.447,0)"><use xlink:href="#g190-106"/></g><g transform="matrix(.013,0,0,-0.013,9.971,0)"><use xlink:href="#g190-98"/></g><g transform="matrix(.013,0,0,-0.013,15.638,0)"><use xlink:href="#g190-116"/></g><g transform="matrix(.013,0,0,-0.013,24.118,0)"><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="16.257pt" style="vertical-align:-0.6369991pt" height="9.9449pt" version="1.1" viewBox="35.3311838 -9.3079 16.257 9.9449"><g transform="matrix(.013,0,0,-0.013,35.381,0)"><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,-0.013,41.622,0)"><use xlink:href="#g121-35"/></g></svg>).</span></span> While these are preliminary results from a small sample of patients with PD (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="17.789pt" style="vertical-align:-0.2063999pt" id="M9" height="8.32035pt" version="1.1" viewBox="-0.0498162 -8.11395 17.789 8.32035"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-111" d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"/></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><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="6.416pt" style="vertical-align:-0.2063999pt" height="8.32035pt" version="1.1" viewBox="21.3711838 -8.11395 6.416 8.32035"><g transform="matrix(.013,0,0,-0.013,21.421,0)"><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></span> this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [<sup>18</sup>F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.

Sarah L. Martin

Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [<sup>18</sup>F]SynVesT-1 PET in Parkinson’s Disease

Magnetic particle imaging (MPI) is a new tracer-based imaging modality that is useful in diagnosing various pathophysiology related to the vascular system and for sensitive tracking of cytotherapies. MPI uses nonradioactive and easily assimilated nanometer-sized iron oxide particles as tracers. MPI images the nonlinear Langevin behavior of the iron oxide particles and has allowed for the sensitive detection of iron oxide-labeled therapeutic cells in the body. This review will provide an overview of MPI technology, the tracer, and its use in vascular imaging and cytotherapies using molecular targets.

Prashant Chandrasekharan

Renesmee Kuo

K. L. Barry Fung

Chinmoy Saayujya

Jacob Bryan

Mariam Yousuf

Benjamin Fellows

Caylin Colson

Quincy Huynh

Owen Doyle

Allison Hartley

Khadija Yousuf

Patrick Goodwill

Steven Conolly

Magnetic Particle Imaging in Vascular Imaging, Immunotherapy, Cell Tracking, and Noninvasive Diagnosis

Noninvasive monitoring of allograft rejection is beneficial for the prognosis of patients with organ transplantation. Recently, IL-27/IL-27R<i>α</i> was proved in close relation with inflammatory diseases, and <sup>125</sup>I-anti-IL-27R<i>α</i> mAb our group developed demonstrated high accumulation in the rejection of the allograft. However, antibody imaging has limitations in the imaging background due to its large molecular weight. Therefore, we developed a novel radiotracer (iodine-125-labeled recombinant IL-27) to evaluate the advantage in the targeting and imaging of allograft rejection. In vitro specific binding of <sup>125</sup>I-rIL-27 was determined by saturation and competitive assay. Blood clearance, biodistribution, phosphor autoradioimaging, and IL-27R<i>α</i> expression were studied on day 10 after transplantation (top period of allorejection). Our results indicated that <sup>125</sup>I-rIL-27 could bind with IL-27R<i>α</i> specifically and selectively in vitro. The blood clearance assay demonstrated fast blood clearance with 13.20 <i>μ</i>l/h of <sup>125</sup>I-rIL-27 staying in the blood after 24 h. The whole-body phosphor autoradiography and biodistribution assay indicated a higher specific uptake of <sup>125</sup>I-rIL-27 and a clear radioimage in allograft than in syngraft at 24 h, while a similar result was obtained at 48 h in the group of <sup>125</sup>I-anti-IL-27R<i>α</i> mAb injection. Meanwhile, a higher expression of IL-27R<i>α</i> was found in the allograft by Western blot. The accumulation of radioactivity of <sup>125</sup>I-rIL-27 was highly correlated with the expression of IL-27R<i>α</i> in the allograft. In conclusion, <sup>125</sup>I-rIL-27 could be a promising probe for acutely monitoring allograft rejection with high specific binding towards IL-27R<i>α</i> on allograft and low imaging background.

Shanshan Zhao

Qian Liu

Feng Gao

Guihua Hou

Development and Evaluation of a Novel Radiotracer <sup>125</sup>I-rIL-27 to Monitor Allotransplant Rejection by Specifically Targeting IL-27R<i>α</i>

<i>Purpose</i>. Study the effects of 13-cis-retinoic acid (13-RA), a synthetic analogue of a vitamin A used for the treatment of severe acne, on the blood flow in the rat brain using technetium-99m hexamethyl propylene amine oxime (<sup>99m</sup>Tc-HMPAO) imaging. <i>Methods</i>. A total of 30 adult male Wistar rats were divided into the control (C), low-dose (L), and high-dose (H) groups. The L and H rats were exposed subcutaneously to 0.3 and 0.5 mg, respectively, of 13-RA per kg of body weight for seven days. Brain blood flow imaging was performed using a gamma camera. Then, a region of interest (ROI) around the brain (target, T), a whole-body region (WB), and a background region (BG) was selected and delimited. The net <sup>99m</sup>Tc-HMPAO brain counts were calculated as the net target counts, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="37.582pt" style="vertical-align:-2.26807pt" id="M1" height="11.5564pt" version="1.1" viewBox="-0.0498162 -9.28833 37.582 11.5564"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-79" d="M719 650H483V622C553 619 576 606 581 560C585 532 588 487 588 394V148H585L167 650H20V622C67 618 88 610 109 585C127 562 129 557 129 484V264C129 173 126 124 123 93C118 44 92 31 35 28V0H272V28C204 32 181 44 176 95C173 124 170 172 170 264V515H172L598 -9H629V394C629 487 631 532 635 563C639 606 663 619 719 622V650Z"/></g><g transform="matrix(.013,0,0,-0.013,9.659,0)"><path id="g190-85" d="M592 498C586 556 582 629 581 675H560C545 656 537 650 510 650H115C87 650 74 652 60 675H40C38 620 33 555 28 495H57C69 539 77 568 89 585C102 607 122 616 205 616H267V123C267 44 259 34 168 28V0H454V28C360 34 352 44 352 123V616H422C498 616 514 608 531 584C542 568 552 543 562 495L592 498Z"/></g><g transform="matrix(.013,0,0,-0.013,17.576,0)"><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,-0.013,29.951,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="53.109pt" style="vertical-align:-2.26807pt" height="11.5564pt" version="1.1" viewBox="41.164183799999996 -9.28833 53.109 11.5564"><g transform="matrix(.013,0,0,-0.013,41.214,0)"><path id="g113-41" d="M300 -147C201 -63 143 98 143 270S200 602 300 686L282 710C136 610 70 450 70 271V270C70 89 136 -72 282 -170L300 -147Z"/></g><g transform="matrix(.013,0,0,-0.013,45.712,0)"><use xlink:href="#g190-85"/></g><g transform="matrix(.013,0,0,-0.013,56.669,0)"><path id="g117-33" d="M535 230V280H52V230H535Z"/></g><g transform="matrix(.013,0,0,-0.013,67.205,0)"><path id="g190-67" d="M372 352C427 368 507 407 507 502C507 548 486 592 451 616C420 638 376 650 301 650H44V622C124 616 128 610 128 527V123C128 40 122 34 36 28V0H257C336 0 402 12 453 40C512 72 548 124 548 191C548 291 471 335 372 350V352ZM213 362V558C213 591 216 602 226 608C235 614 258 618 282 618C377 618 415 558 415 490C415 406 369 362 260 362H213ZM213 328H258C380 328 450 283 450 181C450 76 377 35 296 34C231 34 213 53 213 125V328Z"/></g><g transform="matrix(.013,0,0,-0.013,75.11,0)"><path id="g190-72" d="M692 302H438V274C537 267 543 260 543 188V103C543 61 531 48 511 37C489 26 458 20 424 20C231 20 146 188 146 333C146 517 258 630 411 630C507 630 582 597 606 474L634 480C627 546 622 601 619 636C586 643 510 665 426 665C230 665 44 552 44 321C44 122 191 -15 411 -15C491 -15 573 7 635 21C629 49 628 81 628 116V202C628 261 632 266 692 274V302Z"/></g><g transform="matrix(.013,0,0,-0.013,84.469,0)"><path id="g113-42" d="M275 270C275 450 212 609 64 710L45 686C145 604 203 442 203 270S147 -63 45 -147L64 -170C213 -68 275 89 275 270Z"/></g><g transform="matrix(.013,0,0,-0.013,88.967,0)"><path id="g113-48" d="M368 703H309L44 -163H104L368 703Z"/></g></svg><span class="isep"/><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="60.312pt" style="vertical-align:-2.26807pt" height="11.5564pt" version="1.1" viewBox="94.27818380000001 -9.28833 60.312 11.5564"><g transform="matrix(.013,0,0,-0.013,94.328,0)"><use xlink:href="#g113-41"/></g><g transform="matrix(.013,0,0,-0.013,98.826,0)"><path id="g190-88" d="M956 650H736V622C814 613 818 602 804 542C789 471 733 275 691 141H689C628 314 570 476 514 641H485C434 478 377 312 323 142H321C277 284 238 419 199 554C184 605 186 613 259 622V650H16V622C77 615 92 606 117 524C172 346 228 170 281 -11H312C363 151 419 312 475 488H477C528 343 597 150 652 -11H683C765 269 826 458 848 522C878 605 887 613 956 622V650Z"/></g><g transform="matrix(.013,0,0,-0.013,111.449,0)"><use xlink:href="#g190-67"/></g><g transform="matrix(.013,0,0,-0.013,122.074,0)"><use xlink:href="#g117-33"/></g><g transform="matrix(.013,0,0,-0.013,132.611,0)"><use xlink:href="#g190-67"/></g><g transform="matrix(.013,0,0,-0.013,140.516,0)"><use xlink:href="#g190-72"/></g><g transform="matrix(.013,0,0,-0.013,149.874,0)"><use xlink:href="#g113-42"/></g></svg></span> in all groups. At the end of the <sup>99m</sup>Tc-HMPAO brain blood flow imaging, the brain, heart, kidney, lung, and liver were rapidly removed, and their uptake was determined. Brain histopathological analysis was performed using hematoxylin and eosin stains. In addition, the plasma fatty acids were studied using gas chromatography/mass spectrometry. <i>Results</i>. There were highly significant differences between L and H in comparison to C and across the groups. The <sup>99m</sup>Tc-HMPAO radioactivity in the brain showed increased uptake in a dose-dependent manner. There were also significant changes in the brain tissues and decreased free fatty acids among the groups compared to C. <i>Conclusion</i>. 13-RA increases <sup>99m</sup>TcHMPAO brain perfusion, uptake, and function and reduces fatty acids.

Fatma Al-Saeedi

Peramaiyan Rajendran

13-<i>cis</i>-Retinoic Acid Affects Brain Perfusion and Function: In Vivo Study

<i>Objective</i>. Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is overexpressed in various cancers which has led to the development of therapeutic anti-Siglec-15 monoconal antibodies (mAbs). In these preclinical studies, the therapeutic mAb, NC318 (antihuman/murine Siglec-15 mAb), was labeled with zirconium-89 and evaluated in human Siglec-15 expressing cancer cells and mouse xenografts for potential use as a clinical diagnostic imaging agent. <i>Methods</i>. Desferrioxamine-conjugated NC318 was radiolabeled with zirconium-89 to synthesize [<sup>89</sup>Zr]Zr-DFO-NC318. Cancer cell lines expressing variable Siglec-15 levels were used for in vitro cell binding studies and tumor xenograft mouse models for biodistributions. [<sup>89</sup>Zr]Zr-DFO-NC318 biodistribution and PET imaging studies to determine tissue uptakes (tissue : muscle ratios, T : M) included pharmacokinetic evaluation in Siglec-15+tumor xenografts and immunocompetent mice, blocking with nonradioactive NC318 (20, 100, and 300 <i>μ</i>g) and xenografts with low/negligible Siglec-15 expressing tumors. <i>Results</i>. [<sup>89</sup>Zr]Zr-DFO-NC318 exhibited high affinity (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.291101pt" id="M1" height="11.927pt" version="1.1" viewBox="-0.0498162 -8.6359 15.014 11.927" width="15.014pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-76" d="M743 650H503L496 622L527 618C563 613 564 603 532 573C449 495 371 431 323 392C301 374 272 355 246 346L280 522C297 609 300 614 379 622L385 650H135L129 622C209 614 215 609 198 522L124 133C106 39 99 35 23 28L17 0H271L277 28C193 35 192 39 208 133L239 316C264 328 280 325 303 288C368 183 435 90 502 0H652L659 28C602 34 584 43 543 94C495 154 403 283 347 369L574 554C634 603 659 612 735 624L743 650Z"/></g><g transform="matrix(.0091,0,0,-0.0091,9.23,3.132)"><path id="g50-101" d="M538 684C542 703 539 710 529 710C512 710 455 682 363 674L361 644H396C444 644 448 642 438 594L405 438C373 450 347 451 336 451C288 451 200 416 147 374C69 312 24 207 24 113C24 29 60 -12 94 -12C126 -12 156 4 196 30C231 53 296 100 346 166H348L328 81C311 10 325 -12 348 -12C380 -12 450 24 512 98L495 125C466 97 431 70 417 70C408 70 408 80 411 98L538 684ZM390 373L361 240C336 196 210 56 145 56C132 56 113 73 113 131C113 216 156 338 220 379C243 394 266 402 303 402C331 402 375 388 390 373Z"/></g></svg>~4 nM) for Siglec-15 and distinguished between moderate and negligible Siglec-15 expression levels in cancer cell lines. The highest [<sup>89</sup>Zr]Zr-DFO-NC318 uptakes occurred in the spleen and lymph nodes of the Siglec-15+tumor xenografts at all time points followed by Siglec-15+tumor uptake which was lower although highly retained. In immunocompetent mice, the spleen and lymph nodes exhibited lower uptakes indicating that the athymic xenografts had increased Siglec-15+ immune cells. Specific [<sup>89</sup>Zr]Zr-DFO-NC318 binding to Siglec-15 was proven with NC318 blocking studies in which dose-dependent decreases in Siglec-15+tumor T : Ms were observed. Higher than expected, tumor T : Ms were seen in lower expressing tumors likely due to the contribution of murine Siglec-15+ immune cells in the tumor microenvironment as confirmed by immunohistochemistry. Siglec-15+tumors were identified on PET images whereas low/negligible expressing tumors showed lower uptakes. <i>Conclusions</i>. In vitro and in vivo [<sup>89</sup>Zr]Zr-DFO-NC318 uptakes correlated with Siglec-15 expression levels in target tissues. Despite uptake in immune cell subsets in the tumor microenvironment, these results suggest that clinical [<sup>89</sup>Zr]Zr-DFO-NC318 PET imaging may have value in selecting patients for Siglec-15-targeted therapies.

Elaine M. Jagoda

Falguni Basuli

Colleen Olkowski

Ido Weiss

Tim E. Phelps

Karen Wong

Anita Thien Ton

Kelly C. Lane

Steve Adler

Donna Butcher

Elijah F. Edmondson

Sol Langermann

Peter L. Choyke

Immuno-PET Imaging of Siglec-15 Using the Zirconium-89-Labeled Therapeutic Antibody, NC318

About this journal

<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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<p><em>Molecular Imaging</em> is an official journal of the Society of Nuclear Medicine and Molecular Imaging (SNMMI).</p>


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Molecular Imaging - Table of contents 2023

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