Radioiodination of 5-aminoisoquinoline for Poly (ADP-ribose) Polymerase Targeting: An In vitro Evaluation in Colorectal Carcinoma Cells

Document Type : Original Article

Authors

1 Cyclotron Project, Nuclear Research Center, Atomic Energy Authority, Egypt

2 Drug Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Egypt

3 Cyclotron Project, Egyptian Atomic Energy Authority Labeled Compounds Department, Hot Labs Center, Atomic Energy Authority, Egypt

4 Labeled Compounds Department, Hot Labs Center, Atomic Energy Authority, Egypt

Abstract

THE ISOQUINOLINE derivative, 5-aminoisoquinoline (5-AIQ), is a potent inhibitor of poly (ADP-ribose) polymerase (PARP) activity; the DNA repairing protein frequently overexpressed in various carcinoma cells. The current study is dedicated for developing a highly specific radioiodinated PARP-1 binding tracer namlely, [131I] 5-aminoisoquinoline. The radioiodination of 5-aminoisoquinoline with 131I was carried out via electrophilic substitution reaction. In order to achieve the maximum radioiodination, the parameters including 5-aminoisoquinoline concentration, oxidizing agent, reaction time, temperature and type of solvent were optimized. the radiochemical purity was determined by high performance liquid chromatography (HPLC) using Reversed phase lichrosorb column 250×4.6 mm, C-18 5 μm. The maximum radiochemical yield was 80% with radiochemical purity reached 98%. The log P value for [131I] 5-aminoisoquinoline was found to be 2.08 ± 0.79. Data presented from Cell viability (MTT) cytotoxicity assay on Caco-2 cells showed matched IC50 values with the selected drug concentrations profile for either labeled or unlabeled 5-aminoisoquinoline. Likewise, the radioiodinated 5-aminoisoquinoline elucidated a higher cell uptake compared to free I-131.

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