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 - 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 - https://www.scopus.com/pages/publications/85069935162
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 -
