Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [<sup>18</sup>F]Fluoro-PEG-Folate

<div>Representative immunofluorescence images of <svg height="14.2262pt" id="M88" style="vertical-align:-3.429501pt" version="1.1" viewbox="-0.0498162 -10.7967 28.8966 14.2262" width="28.8966pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z" id="g121-68"></path></g><g transform="matrix(.013,0,0,-0.013,6.877,0)"><path d="M631 18C609 24 585 35 559 65C534 91 514 117 478 169C448 214 406 281 389 313C462 346 516 399 516 485C516 545 490 590 449 616C412 641 363 650 290 650H42V622C120 615 128 612 128 527V125C128 40 120 34 38 28V0H300V28C221 34 212 40 212 125V284H244C295 284 312 272 329 244C359 195 395 133 430 84C475 19 516 -3 592 -7C603 -8 615 -8 627 -8L631 18ZM212 316V563C212 591 215 602 223 607C231 613 248 617 277 617C352 617 423 577 423 469C423 415 407 375 368 345C343 324 310 316 260 316H212Z" id="g121-80"></path></g><g transform="matrix(.013,0,0,-0.013,15.08,0)"><path d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z" id="g113-224"></path></g><g transform="matrix(.0091,0,0,-0.0091,22.635,-5.741)"><path d="M556 236V289H337V504H275V289H56V236H275V-4H337V236H556Z" id="g54-36"></path></g></svg> macrophages in spleen sections of healthy (<svg height="8.55521pt" id="M89" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 27.8368 8.55521" width="27.8368pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path 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" id="g113-111"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z" id="g117-34"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path 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" id="g113-52"></path></g></svg>) and saline- (<svg height="8.55521pt" id="M90" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 27.8368 8.55521" width="27.8368pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path 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" id="g113-111"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z" id="g117-34"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z" id="g113-53"></path></g></svg>) and MTX-treated (<svg height="8.55521pt" id="M91" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 27.8368 8.55521" width="27.8368pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path 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" id="g113-111"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z" id="g117-34"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z" id="g113-53"></path></g></svg>) rats. ((a), (b)) Images represent <svg height="14.2262pt" id="M92" style="vertical-align:-3.429501pt" version="1.1" viewbox="-0.0498162 -10.7967 28.8966 14.2262" width="28.8966pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z" id="g121-68"></path></g><g transform="matrix(.013,0,0,-0.013,6.877,0)"><path d="M631 18C609 24 585 35 559 65C534 91 514 117 478 169C448 214 406 281 389 313C462 346 516 399 516 485C516 545 490 590 449 616C412 641 363 650 290 650H42V622C120 615 128 612 128 527V125C128 40 120 34 38 28V0H300V28C221 34 212 40 212 125V284H244C295 284 312 272 329 244C359 195 395 133 430 84C475 19 516 -3 592 -7C603 -8 615 -8 627 -8L631 18ZM212 316V563C212 591 215 602 223 607C231 613 248 617 277 617C352 617 423 577 423 469C423 415 407 375 368 345C343 324 310 316 260 316H212Z" id="g121-80"></path></g><g transform="matrix(.013,0,0,-0.013,15.08,0)"><path d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z" id="g113-224"></path></g><g transform="matrix(.0091,0,0,-0.0091,22.635,-5.741)"><path d="M556 236V289H337V504H275V289H56V236H275V-4H337V236H556Z" id="g54-36"></path></g></svg> macrophages in the spleen of saline-treated and MTX-treated rats, respectively. ((c), (d)) Isotype control stained spleen sections of saline-treated and MTX-treated rats, respectively. (e) Bar graph representation of quantifications of <svg height="14.2262pt" id="M93" style="vertical-align:-3.429501pt" version="1.1" viewbox="-0.0498162 -10.7967 28.8966 14.2262" width="28.8966pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z" id="g121-68"></path></g><g transform="matrix(.013,0,0,-0.013,6.877,0)"><path d="M631 18C609 24 585 35 559 65C534 91 514 117 478 169C448 214 406 281 389 313C462 346 516 399 516 485C516 545 490 590 449 616C412 641 363 650 290 650H42V622C120 615 128 612 128 527V125C128 40 120 34 38 28V0H300V28C221 34 212 40 212 125V284H244C295 284 312 272 329 244C359 195 395 133 430 84C475 19 516 -3 592 -7C603 -8 615 -8 627 -8L631 18ZM212 316V563C212 591 215 602 223 607C231 613 248 617 277 617C352 617 423 577 423 469C423 415 407 375 368 345C343 324 310 316 260 316H212Z" id="g121-80"></path></g><g transform="matrix(.013,0,0,-0.013,15.08,0)"><path d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z" id="g113-224"></path></g><g transform="matrix(.0091,0,0,-0.0091,22.635,-5.741)"><path d="M556 236V289H337V504H275V289H56V236H275V-4H337V236H556Z" id="g54-36"></path></g></svg> macrophages in spleen of saline-treated and MTX-treated rats. Values depict mean numbers of macrophages counted in predefined areas of the spleen.<i> Error bars</i> indicate SD. (blue color: DAPI (nuclear staining); green color: FR<svg height="12.7178pt" id="M94" style="vertical-align:-3.42947pt" version="1.1" viewbox="-0.0498162 -9.28833 7.68094 12.7178" width="7.68094pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z" id="g113-224"></path></g></svg> staining). <span class="nowrap"><svg height="11.7782pt" id="M95" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 44.5261 11.7782" width="44.5261pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path 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" id="g113-113"></path></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z" id="g117-91"></path></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><path 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" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z" id="g113-47"></path></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><path 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" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z" id="g113-50"></path></g></svg>.</span></div>

Contrast Media & Molecular Imaging

fig6

Figure 6

Figure 6: Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [<sup>18</sup>F]Fluoro-PEG-Folate 

Figure 6 | Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [18F]Fluoro-PEG-Folate 