Multimodality Agents for Tumor Imaging (PET,Fluorescence) and Photodynamic Therapy.A Possible 'See and Treat' Approach

摘要

Methyl 3-(1'-m-iodobenzyloxyethyl)-3-devinylpyropheophorbide-a (2),obtained in a sequence of reactions from pyropheophorbide-a (a chlorophyll-a derivative),was found to be a promising imaging agent and a photosensitizer for photodynamic therapy (PDT).The electrophillic aromatic iodination of the corresponding trimethylstannyl intermediate with Na~(124)I in the presence of an Iodogen bead afforded ~(124)I-labeled photosensitizer 4 with >95% radioactive specificity.In addition to drug-uptake,the light fluence and fluence rate that were used for the light treatment had a significant impact in long-term tumor cure.The iodo photosensitizer 2 (nonlabeled analogue of 4) produced 100% tumor cure (5/5 mice were tumor free on day 60) at a dose of 1.5mumol/kg and a light dose of 128 J/cm~2,14 mW/cm~2 for 2.5 h (lambda_(max) 665 nm) at 24 h postinjection.The photosensitizer also showed promising tumor fluorescence and PET imaging ability.Our present work demonstrates the utility of the first ~(124)I-labeled photosensitizer as a "multimodality agent",which could further be improved by using more tumor-avid and/or target-specific photosensitizers.