Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, India.
Photodynamic Therapy Center, Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Molecules. 2023 Apr 27;28(9):3782. doi: 10.3390/molecules28093782.
To investigate and compare the pharmacokinetic profile and anti-cancer activity of fluorinated and iodinated photosensitizers (PSs), the 3-(1'-(-fluorobenzyloxy)ethyl pyropheophorbide and the corresponding meta-(-) and para (-) fluorinated analogs (methyl esters and carboxylic acids) were synthesized. Replacing iodine with fluorine in PSs did not make any significant difference in fluorescence and singlet oxygen (a key cytotoxic agent) production. The nature of the delivery vehicle and tumor types showed a significant difference in uptake and long-term cure by photodynamic therapy (PDT), especially in the iodinated PS. An unexpected difference in the pharmacokinetic profiles of fluorinated vs. iodinated PSs was observed. At the same imaging parameters, the fluorinated PSs showed maximal tumor uptake at 2 h post injection of the PS, whereas the iodinated PS gave the highest uptake at 24 h post injection. Among all isomers, the -fluoro PS showed the best in vivo anti-cancer activity in mice bearing U87 (brain) or bladder (UMUC3) tumors. A direct correlation between the tumor uptake and PDT efficacy was observed. The higher tumor uptake of -fluoro PS at two hours post injection provides a solid rationale for developing the corresponding F-agent (half-life 110 min only) for positron imaging tomography (PET) of those cancers (e.g., bladder, prostate, kidney, pancreas, and brain) where F-FDG-PET shows limitations.
为了研究和比较氟化和碘化光敏剂（PSs）的药代动力学特征和抗癌活性，合成了 3-（1′-（-氟苯甲氧基）乙基焦脱镁叶绿酸和相应的间-（-）和对-（-）氟代类似物（甲酯和羧酸）。在 PSs 中用氟取代碘并没有在荧光和单线态氧（一种关键的细胞毒性剂）产生方面产生任何显著差异。给药载体和肿瘤类型的性质在光动力疗法（PDT）的摄取和长期治愈方面表现出显著差异，尤其是在碘化 PS 中。观察到氟代 PS 与碘代 PS 的药代动力学特征存在意外差异。在相同的成像参数下，氟代 PS 在注射 PS 后 2 小时显示出最大的肿瘤摄取，而碘代 PS 在注射后 24 小时显示出最高的摄取。在所有异构体中，-氟代 PS 在携带 U87（脑）或膀胱癌（UMUC3）的小鼠中表现出最佳的体内抗癌活性。观察到肿瘤摄取与 PDT 疗效之间存在直接相关性。在注射后两小时内氟代 PS 的更高肿瘤摄取为开发相应的 F-试剂（半衰期仅 110 分钟）提供了坚实的理由，用于那些氟代 FDG-PET 显示局限性的癌症（如膀胱、前列腺、肾脏、胰腺和脑）的正电子成像断层扫描（PET）。
