Abstract |
Two positional isomers of purpurinimide, 3-[1'-(3-iodobenzyloxyethyl)] purpurin-18-N-hexylimide methyl ester 4, in which the iodobenzyl group is present at the top half of the molecule (position-3), and a 3-(1'-hexyloxyethy) purpurin-18-N-(3-iodo-benzylimide)] methyl ester 5, where the iodobenzyl group is introduced at the bottom half (N-substitued cyclicimide) of the molecule, were derived from chlorophyll-a. The tumor uptake and phototherapeutic abilities of these isomers were compared with the pyropheophorbide analogue 1 (lead compound). These compounds were then converted into the corresponding 124I-labeled PET imaging agents with specific activity >1 Ci/micromol. Among the positional isomers 4 and 5, purpurinimide 5 showed enhanced imaging and therapeutic potential. However, the lead compound 1 derived from pyropheophorbide-a exhibited the best PET imaging and PDT efficacy. For investigating the overall lipophilicity of the molecule, the 3-O-hexyl ether group present at position-3 of purpurinimide 5 was replaced with a methyl ether substituent, and the resulting product 10 showed improved tumor uptake, but due to its significantly higher uptake in the liver, spleen, and other organs, a poor tumor contrast in whole-body tumor imaging was observed.
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Authors | Suresh K Pandey, Munawwar Sajjad, Yihui Chen, Anupam Pandey, Joseph R Missert, Carrie Batt, Rutao Yao, Hani A Nabi, Allan R Oseroff, Ravindra K Pandey |
Journal | Bioconjugate chemistry
(Bioconjug Chem)
Vol. 20
Issue 2
Pg. 274-82
(Feb 2009)
ISSN: 1520-4812 [Electronic] United States |
PMID | 19191565
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anthraquinones
- Iodine Radioisotopes
- Iodobenzenes
- Photosensitizing Agents
- Chlorophyll
- iodobenzene
- purpurin
- Chlorophyll A
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Topics |
- Animals
- Anthraquinones
(chemistry, pharmacokinetics, therapeutic use)
- Chlorophyll
(chemistry, pharmacokinetics, therapeutic use)
- Chlorophyll A
- Iodine Radioisotopes
(chemistry)
- Iodobenzenes
(chemistry)
- Isomerism
- Mice
- Neoplasms
(diagnostic imaging, drug therapy, metabolism)
- Photochemotherapy
- Photosensitizing Agents
(chemistry, pharmacokinetics, therapeutic use)
- Positron-Emission Tomography
- Tissue Distribution
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