Multimodality agents for tumor imaging (PET, fluorescence) and photodynamic therapy. A possible "see and treat" approach.
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.
Pandey
Suresh K
SK
PDT Center and Department of Dermatology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Gryshuk
Amy L
AL
Sajjad
Munawwar
M
Zheng
Xiang
X
Chen
Yihui
Y
Abouzeid
Mohei M
MM
Morgan
Janet
J
Charamisinau
Ivan
I
Nabi
Hani A
HA
Oseroff
Allan
A
Pandey
Ravindra K
RK
D000818:Animals; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005453:Fluorescence; D006207:Half-Life; D007457:Iodine Radioisotopes; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049268:Positron-Emission Tomography; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D017319:Photosensitizing Agents; D011963:Receptors, GABA-A; C505556:methyl 3-(1'-3-iodobenzyloxyethyl)-3-devinylpyropheophorbide-a; D002734:Chlorophyll