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

Aimee J. Marko, Mykhaylo Dukh, Nayan J. Patel, Joseph R. Missert, Tymish Ohulchanskyy, Walter A. Tabaczynski, Kei Ohkubo, Shunichi Fukuzumi, Rutao Yao, Munawwar Sajjad, Ravindra K. Pandey

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1503-1513
Number of pages11
JournalChemMedChem
Volume14
Issue number16
DOIs
StatePublished - 20 Aug 2019

Bibliographical note

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

Keywords

  • photodynamic therapy
  • photosensitizers
  • positron emission tomography
  • reactive oxygen species
  • relative uptake volume

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