Multimodality Agents for Tumor Imaging (PET, Fluorescence) and Photodynamic Therapy. A Possible “See and Treat” Approach
- 7 September 2005
- journal article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 48 (20), 6286-6295
- https://doi.org/10.1021/jm050427m
Abstract
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 Na124I in the presence of an Iodogen bead afforded 124I-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 μmol/kg and a light dose of 128 J/cm2, 14 mW/cm2 for 2.5 h (λmax 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 124I-labeled photosensitizer as a “multimodality agent”, which could further be improved by using more tumor-avid and/or target-specific photosensitizers.Keywords
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