jm2c00417_si_001.pdf (431.28 kB)
Nontoxic Tumor-Targeting Optical Agents for Intraoperative Breast Tumor Imaging
journal contributionposted on 2022-05-11, 19:06 authored by Samer A. Naffouje, Masahide Goto, Lori U. Coward, Gregory S. Gorman, Konstantin Christov, Jing Wang, Albert Green, Anne Shilkaitis, Tapas K. Das Gupta, Tohru Yamada
Precise identification of the tumor margins during breast-conserving surgery (BCS) remains a challenge given the lack of visual discrepancy between malignant and surrounding normal tissues. Therefore, we developed a fluorescent imaging agent, ICG-p28, for intraoperative imaging guidance to better aid surgeons in achieving negative margins in BCS. Here, we determined the pharmacokinetics (PK), biodistribution, and preclinical toxicity of ICG-p28. The PK and biodistribution of ICG-p28 indicated rapid tissue uptake and localization at tumor lesions. There were no dose-related effect and no significant toxicity in any of the breast cancer and normal cell lines tested. Furthermore, ICG-p28 was evaluated in clinically relevant settings with transgenic mice that spontaneously developed invasive mammary tumors. Intraoperative imaging with ICG-p28 showed a significant reduction in the tumor recurrence rate. This simple, nontoxic, and cost-effective method can offer a new approach that enables surgeons to intraoperatively identify tumor margins and potentially improves overall outcomes by reducing recurrence rates.
targeting optical agentssurrounding normal tissuesreducing recurrence ratesclinically relevant settingsfluorescent imaging agentbetter aid surgeonsachieving negative marginstumor recurrence rateintraoperative imaging guidancepk ), biodistributionintraoperative imagingtumor marginsenables surgeonstumor lesionsvisual discrepancytransgenic micesignificant toxicitysignificant reductionrelated effectpreclinical toxicitynew approacheffective methodconserving surgerychallenge given