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A Pyropheophorbide Analogue Containing a Fused Methoxy Cyclohexenone Ring System Shows Promising Cancer-Imaging Ability.
- Source :
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ChemMedChem [ChemMedChem] 2019 Aug 20; Vol. 14 (16), pp. 1503-1513. Date of Electronic Publication: 2019 Jul 25. - Publication Year :
- 2019
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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 <superscript>124</superscript> I isotope). The PET imaging ability and ex vivo biodistribution of [ <superscript>124</superscript> I]4 were compared with the well-studied methyl [3-( <superscript>124</superscript> 1'-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [ <superscript>124</superscript> I]2) and [ <superscript>18</superscript> F]fluorodeoxyglucose ([ <superscript>18</superscript> F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [ <superscript>124</superscript> 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 [ <superscript>18</superscript> F]FDG and [ <superscript>124</superscript> I]2 in 2 % ethanol formulation, [ <superscript>124</superscript> 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 [ <superscript>124</superscript> 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 [ <superscript>18</superscript> F]FDG shows limitations.<br /> (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Animals
Contrast Media chemical synthesis
Contrast Media pharmacokinetics
Contrast Media radiation effects
Cyclohexanones chemical synthesis
Cyclohexanones pharmacokinetics
Cyclohexanones radiation effects
Female
Light
Mice, Inbred BALB C
Photochemotherapy
Photosensitizing Agents chemical synthesis
Photosensitizing Agents pharmacokinetics
Photosensitizing Agents radiation effects
Porphyrins chemical synthesis
Porphyrins pharmacokinetics
Porphyrins radiation effects
Colonic Neoplasms diagnostic imaging
Colonic Neoplasms drug therapy
Contrast Media pharmacology
Cyclohexanones pharmacology
Photosensitizing Agents pharmacology
Porphyrins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1860-7187
- Volume :
- 14
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- ChemMedChem
- Publication Type :
- Academic Journal
- Accession number :
- 31343840
- Full Text :
- https://doi.org/10.1002/cmdc.201900352