Multimodality agents for tumor imaging (PET, fluorescence) and photodynamic therapy. A possible see and treat approach

Methyl 3-(1'-m-iodobenzyloxyethyl)-3-devinylpyropheophorbide-alpha (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 (NaI)-I-124 in the presence of an Iodogen bead afforded I-124-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 1.5 mu mol/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 I-124-labeled photosensitizer as a multimodality agent, which could further be improved by using more tumor-avid and/or target-specific photosensitizers.