APyropheophorbide Analogue Containing aFused Mepoxy Cyclohexenone Ring System Shows Promising Cancer-Imaging Ability

摘要

Herein we report pe synpesis, photophysical properties, posi- tron emission tomography (PET) imaging and photodynamic perapy (PDT) efficacy of mepyl 3-(1’-m-iodobenzyloxy)epyl-3- devinyl-verdin 4 (wip or wipout pe 124 Iisotope). pe PET imagingability and ex vivobiodistribution of [ 124 I]4 were com- pared wip pe well-studied mepyl [3-( 124 1’-m-iodobenzylox- y)epyl]-3-devinyl-pyropheophorbide-a mepyl ester (PET- ONCO or [ 124 I]2)and [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-bodyPET images of [ 124 I]4 containing afused mepoxy cyclohexenone ring system showed excellent tumor contrastwip time (72>48> 24 hpost-injection). Ex vivo biodistribution results indicate pat relative to pe currentclinical standard [ 18 F]FDG and [ 124 I]2 in 2% epanol formulation, [ 124 I]4,atpe same radioactivedose (25 mCi per mouse), showed highertumor uptake at 24 hpost- injectionand longertumor retention. In biological environ- ments, compound 4 showed lower fluorescenceand lower sin- glet oxygen yield pan 2,which is possibly due to higherag- gregation caused by pe presence of afused cyclohexenone ring system,resulting in limited in vitro/in vivo PDT efficacy. perefore, pe chlorophyll-a analogue[ 124 I]4 provides easy access to anovel PET imaging agent (wip no skin phototoxici- ty) to image cancer types—brain, renal carcinomas, pancreas— in which [ 18 F]FDG shows limitations.