TY - JOUR
T1 - A Pyropheophorbide Analogue Containing a Fused Methoxy Cyclohexenone Ring System Shows Promising Cancer-Imaging Ability
AU - Marko, Aimee J.
AU - Dukh, Mykhaylo
AU - Patel, Nayan J.
AU - Missert, Joseph R.
AU - Ohulchanskyy, Tymish
AU - Tabaczynski, Walter A.
AU - Ohkubo, Kei
AU - Fukuzumi, Shunichi
AU - Yao, Rutao
AU - Sajjad, Munawwar
AU - Pandey, Ravindra K.
N1 - Funding Information:
This work was supported by the US National Institutes of Health (NIH, CA127369 to R.K.P.) and the US National Cancer Institute (NCI) Cancer Center Support Grant CA 016156 to the Roswell Park Comprehensive Cancer Center (RPCCC), Buffalo, NY (USA).
Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/8/20
Y1 - 2019/8/20
N2 - 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 124I isotope). The PET imaging ability and ex vivo biodistribution of [124I]4 were compared with the well-studied methyl [3-(1241′-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [124I]2) and [18F]fluorodeoxyglucose ([18F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [124I]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 [18F]FDG and [124I]2 in 2 % ethanol formulation, [124I]4, at the same radioactive dose (25 μCi 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 [124I]4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types—brain, renal carcinomas, pancreas—in which [18F]FDG shows limitations.
AB - 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 124I isotope). The PET imaging ability and ex vivo biodistribution of [124I]4 were compared with the well-studied methyl [3-(1241′-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [124I]2) and [18F]fluorodeoxyglucose ([18F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [124I]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 [18F]FDG and [124I]2 in 2 % ethanol formulation, [124I]4, at the same radioactive dose (25 μCi 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 [124I]4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types—brain, renal carcinomas, pancreas—in which [18F]FDG shows limitations.
KW - photodynamic therapy
KW - photosensitizers
KW - positron emission tomography
KW - reactive oxygen species
KW - relative uptake volume
UR - http://www.scopus.com/inward/record.url?scp=85069935162&partnerID=8YFLogxK
U2 - 10.1002/cmdc.201900352
DO - 10.1002/cmdc.201900352
M3 - Article
C2 - 31343840
AN - SCOPUS:85069935162
SN - 1860-7179
VL - 14
SP - 1503
EP - 1513
JO - ChemMedChem
JF - ChemMedChem
IS - 16
ER -
