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

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 electrophilic 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 micromol/kg and a light dose of 128 J/cm2, 14 mW/cm2 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 124I-labeled photosensitizer as a "multimodality agent", which could further be improved by using more tumor-avid and/or target-specific photosensitizers.

• Authors: Suresh K Pandey, Amy L Gryshuk, Munawwar Sajjad, Xiang Zheng, Yihui Chen, Mohei M Abouzeid, Janet Morgan, Ivan Charamisinau, Hani A Nabi, Allan Oseroff, Ravindra K Pandey
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 48 Issue 20 Pg. 6286-95 (Oct 06 2005) ISSN: 0022-2623 [Print] United States
• PMID: 16190755 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Iodine Radioisotopes
• Photosensitizing Agents
• Receptors, GABA-A
• methyl 3-(1'-3-iodobenzyloxyethyl)-3-devinylpyropheophorbide-a
• Chlorophyll

Topics

• Animals
• Cell Line, Tumor
• Chlorophyll (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Female
• Fluorescence
• Half-Life
• Iodine Radioisotopes
• Mice
• Mice, Inbred C3H
• Neoplasms, Experimental (diagnosis, drug therapy)
• Photochemotherapy
• Photosensitizing Agents (chemical synthesis, chemistry, pharmacology)
• Positron-Emission Tomography
• Receptors, GABA-A (drug effects, metabolism)
• Tissue Distribution