Compared to Purpurinimides, the Pyropheophorbide Containing an Iodobenzyl Group Showed Enhanced PDT Efficacy and Tumor Imaging (124I-PET) Ability

• Published in: Bioconjugate chemistry 2009-02, Vol.20 (2), p.274-282
• Main Authors: Pandey, Suresh K, Sajjad, Munawwar, Chen, Yihui, Pandey, Anupam, Missert, Joseph R, Batt, Carrie, Yao, Rutao, Nabi, Hani A, Oseroff, Allan R, Pandey, Ravindra K
• Format: Article
• Language: English
• Subjects: Animals; Anthraquinones - chemistry; Anthraquinones - pharmacokinetics; Anthraquinones - therapeutic use; Chemical compounds; Chlorophyll; Chlorophyll - chemistry; Chlorophyll - pharmacokinetics; Chlorophyll - therapeutic use; Chlorophyll A; Iodine Radioisotopes - chemistry; Iodobenzenes - chemistry; Isomerism; Mice; Molecular chemistry; Neoplasms - diagnostic imaging; Neoplasms - drug therapy; Neoplasms - metabolism; Photochemotherapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - therapeutic use; Photosynthesis; Positron-Emission Tomography; Tissue Distribution; Tumors
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc8003638

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/μmol. 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 presnt 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.