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

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 analog 1 (lead compound). These compounds were then converted into the corresponding 124 I-labeled PET imaging agents with specific activity >1Ci/ μmole. 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 liver, spleen and other organs, a poor tumor contrast in whole-body tumor imaging was observed.

Engineering of relevant photodynamic processes through structural modifications of metallotetrapyrrolic photosensitizers

“…The modification of porphyrin ring decreases the energy of the Q absorption band and displaces it into the NIR trial against psoriasis [269][270][271]. A number of metallophthalocyanines proceeded to clinical trials (see Table 6).…”

Development and applications of photo-triggered theranostic agents

“…A simple method to prepare the 124 I-labeled PS is the direct electrophilic aromatic iodination of the trimethylstannyl substituted analogues with Na 124 I in the presence of commercial iodogen beads. Using this strategy, Pandey et al prepared 124 I-labeled pyropheophorbide and purpurinimide analogues with >95% radioactive specificity [43–44]. It was proposed that this radioactive construct could be used for PET and fluorescence imaging as well as PDT.…”

The role of iodine-124 positron emission tomography in molecular imaging

“…124 IIUdR) has been used to measure cell proliferation in vivo in non small cell lung cancer [67] and glioma [68]. 124 Ilabeled-hypericin for imaging protein-kinase C, 2 0 -fluoro-2 0 -deoxy-1b-D-arabinofuranosyl-5-[ 124 I]iodouracil ( 124 I-FIAU) for imaging herpes virus thymidine kinase [69], (E)-But-2-enedioic acid [4-(3-[( 124 )I]iodoanilino)-quinazolin-6-yl]-amide-(3-morpholin-4-yl-propyl)-amide ( 124 I-morpholino-IPQA) for imaging EGFR kinase activity [70], 124 I-labeled-6-anilino-quianilino-quinazoline for imaging EGFR Inhibitor, 124 I-labeled Annexin V and MBP Annexin V for imaging of apoptosis [71,72], 124 I-anti-PSCA (prostate stem cell antigen) A11 minibody for imaging of prostate cancer bone metastases [73] and 124 I-labeled purpurinimide derivative for tumor imaging [74], have been studied in a few subjects in each instance, 124 I-iodometomidate ( 124 I-IMTO) appears to be an attractive PET tracer for imaging adrenals [75].…”