Premium
A Pyropheophorbide Analogue Containing a Fused Methoxy Cyclohexenone Ring System Shows Promising Cancer‐Imaging Ability
Author(s) -
Marko Aimee J.,
Dukh Mykhaylo,
Patel Nayan J.,
Missert Joseph R.,
Ohulchanskyy Tymish,
Tabaczynski Walter A.,
Ohkubo Kei,
Fukuzumi Shunichi,
Yao Rutao,
Sajjad Munawwar,
Pandey Ravindra K.
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900352
Subject(s) - biodistribution , in vivo , photodynamic therapy , positron emission tomography , ex vivo , chemistry , phototoxicity , nuclear medicine , in vitro , medicine , biochemistry , biology , microbiology and biotechnology , organic chemistry
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 124 I isotope). The PET imaging ability and ex vivo biodistribution of [ 124 I] 4 were compared with the well‐studied methyl [3‐( 124 1′‐ m ‐iodobenzyloxy)ethyl]‐3‐devinyl‐pyropheophorbide‐ a methyl ester (PET‐ONCO or [ 124 I] 2 ) and [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) in BALB/c mice bearing colon‐26 tumors. Whole‐body PET images of [ 124 I] 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 [ 18 F]FDG and [ 124 I] 2 in 2 % ethanol formulation, [ 124 I] 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 [ 124 I] 4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types—brain, renal carcinomas, pancreas—in which [ 18 F]FDG shows limitations.