Preclinical Evaluation and Monitoring of the Therapeutic Response of a Dual Targeted Hyaluronic Acid Nanodrug

<div><svg height="11.439pt" id="M37" style="vertical-align:-2.15067pt" version="1.1" viewbox="-0.0498162 -9.28833 24.031 11.439" width="24.031pt" 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="M290 -163V-135C183 -126 181 -122 181 -44V583C181 662 184 666 290 675V703H120V-163H290Z" id="g113-92"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="345" vert-adv-y="345" xpluscharwidth="4.485"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,4.485,0)"><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><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480" xpluscharwidth="10.725000000000001"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,10.725,0)"><path 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" id="g113-57"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480" xpluscharwidth="16.965"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,16.965,0)"><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><glyph.data ascent="989" descent="-360" horiz-adv-x="529" vert-adv-y="529" xpluscharwidth="23.842"></glyph.data></g></svg>] FDG PET monitoring of HANP/HCPT treatment of MDA-MB-231 tumor. (a) Representative decay-corrected whole-body coronal images of female athymic nude mice with MDA-MB-231 tumors at 1 h after intravenous injection of [<svg height="8.59437pt" id="M38" style="vertical-align:-0.2063894pt" version="1.1" viewbox="-0.0498162 -8.38798 19.5292 8.59437" width="19.5292pt" 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="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><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480" xpluscharwidth="6.24"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><path 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" id="g113-57"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480" xpluscharwidth="12.48"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><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><glyph.data ascent="989" descent="-360" horiz-adv-x="529" vert-adv-y="529" xpluscharwidth="19.357"></glyph.data></g></svg>] FDG on days 0, 3, 7, and 14. (b) Quantitative small-animal PET region-of-interest analysis of tumor uptake of [<svg height="8.59437pt" id="M39" style="vertical-align:-0.2063894pt" version="1.1" viewbox="-0.0498162 -8.38798 19.5292 8.59437" width="19.5292pt" 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="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><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480" xpluscharwidth="6.24"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,6.24,0)"><path 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" id="g113-57"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480" xpluscharwidth="12.48"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,12.48,0)"><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><glyph.data ascent="989" descent="-360" horiz-adv-x="529" vert-adv-y="529" xpluscharwidth="19.357"></glyph.data></g></svg>] FDG in each group. <svg height="6.01072pt" id="M40" style="vertical-align:-0.04980993pt" version="1.1" viewbox="-0.0498162 -5.96091 7.75925 6.01072" width="7.75925pt" 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="M471 153C471 170 463 194 452 212C400 220 373 229 322 255C373 281 400 290 452 298C463 316 471 339 471 357C456 366 431 371 410 370C377 329 356 310 308 279C311 336 317 364 336 413C326 432 310 451 294 459C279 451 262 432 252 413C271 364 277 336 280 279C232 310 211 329 178 370C157 371 132 367 117 357C117 340 125 316 136 298C188 290 215 281 266 255C215 229 188 220 136 212C125 194 117 171 117 153C132 144 157 139 178 140C211 181 232 200 280 231C277 174 271 146 252 97C262 78 278 59 294 51C309 59 326 78 336 97C317 146 311 174 308 231C356 200 377 181 410 140C431 139 456 143 471 153Z" id="g113-43"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="587" vert-adv-y="587" xpluscharwidth="7.631"></glyph.data></g></svg> denotes <svg height="9.2729pt" id="M41" style="vertical-align:-0.6370001pt" version="1.1" viewbox="-0.0498162 -8.6359 44.8393 9.2729" width="44.8393pt" 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="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" id="g113-81"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="617" vert-adv-y="617" xpluscharwidth="8.021"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,11.658,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z" id="g117-91"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="587" vert-adv-y="587" xpluscharwidth="19.289"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,22.921,0)"><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><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480" xpluscharwidth="29.161"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,29.161,0)"><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><glyph.data ascent="3473" descent="-2876" horiz-adv-x="228" vert-adv-y="228" xpluscharwidth="32.125"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,32.125,0)"><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><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480" xpluscharwidth="38.365"></glyph.data></g><g transform="matrix(.013,0,0,-0.013,38.365,0)"><path 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" id="g113-54"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480" xpluscharwidth="44.605000000000004"></glyph.data></g></svg>.</div>

Contrast Media & Molecular Imaging

fig6

Figure 6

Figure 6: Preclinical Evaluation and Monitoring of the Therapeutic Response of a Dual Targeted Hyaluronic Acid Nanodrug 