A Pyropheophorbide Analogue Containing a Fused Methoxy Cyclohexenone Ring System Shows Promising Cancer-Imaging Ability.

Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1 '-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the I-124 isotope). The PET imaging ability and ex vivo biodistribution of [I-124]4 were compared with the well-studied methyl [3-((124)1 '-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [I-124]2) and [F-18]fluorodeoxyglucose ([F-18]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [I-124]4 containing a fused methoxy cyclohexenone ring system showed excellent tumor contrast with time (72>48>24 h post-injection). Ex vivo biodistribution results indicate that relative to the current clinical standard [F-18]FDG and [I-124]2 in 2 % ethanol formulation, [I-124]4, at the same radioactive dose (25 mu Ci per mouse), showed higher tumor uptake at 24 h post-injection and longer tumor retention. In biological environments, compound 4 showed lower fluorescence and lower singlet oxygen yield than 2, which is possibly due to higher aggregation caused by the presence of a fused cyclohexenone ring system, resulting in limited in vitro/in vivo PDT efficacy. Therefore, the chlorophyll-a analogue [I-124]4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types-brain, renal carcinomas, pancreas-in which [F-18]FDG shows limitations.