Radioiodination of Pimonidazole as a Novel Theranostic Hypoxia Probe

Abstract

Background: Tumors are defined as abnormal tissue masses, and one of the most important factors leading to the growth of these abnormal tissue masses is Vascular Endothelial Growth Factor, which stimulates angiogenesis by releasing cells under hypoxic conditions. Hypoxia has a vital role in cancer therapy, thus it is important to monitor hypoxia. The hypoxia marker Pimonidazole (PIM) is a candidate biomarker of cancer aggressiveness. Objective: It is aimed to radioiodinate PIM with Iodine-131 (131I) to join a theranostic approach. For this purpose, PIM was derivatived as PIM-TOS to be able to be radioiodinated. Methods: PIM was derivated via a tosylation reaction. Derivatization product (PIM-TOS) was radioiodinated by using iodogen method and was analyzed by High Performance Liquid Chromatography and Liquid chromatography mass spectrometry. Thin layer radiochromatography was utilized for its quality control studies. Results: PIM was derivatived successfully after the tosylation reaction. The radioiodination yield of PIM-TOS was achieved in yields of over 85 %. Conclusion: In the current study, radioiodination potential of PIM with 131I, as a potential theranostic hypoxia agent was investigated. Further experimental studies should be performed for developing a novel hypoxia probe including theranostics approaches.

Tumor‐penetrating peptide internalizing RGD enhances radiotherapy efficacy through reducing tumor hypoxia

“…For cell proliferation assay, 4T1 cells were seeded into 96‐well plates (10 3 cells/well) and incubated overnight at 37°C and 5% CO 2 . Peptide iRGD was added into the medium at 95 μg/mL (100 μM), according to the published procedures 30,31 . After 4 h, cells were irradiated to 5, 10, or 20 Gy.…”

“…Peptides were injected iv into 4T1 tumor‐bearing mice and pimonidazole hydrochloride (60 mg/kg; Hypoxyprobe Inc., HP1‐100Kit) was administered into mice via iv injection. Pimonidazole is a non‐toxic 2‐nitroimidazole compound that binds thiol groups to proteins, peptides, and amino acids in hypoxic regions, and could be used as an effective exogenous hypoxia probe 31 . Tumors were surgically excised at 1 h after pimonidazole hydrochloride injection.…”

“…Peptide iRGD was added into the medium at 95 μg/mL (100 μM), according to the published procedures. 30 , 31 After 4 h, cells were irradiated to 5, 10, or 20 Gy. Cell proliferation was measured using the Cell Counting Kit‐8 (CCK‐8, KeyGen BioTECH) every other day according to the manufacturer's instructions.…”

“…Pimonidazole is a non‐toxic 2‐nitroimidazole compound that binds thiol groups to proteins, peptides, and amino acids in hypoxic regions, and could be used as an effective exogenous hypoxia probe. 31 Tumors were surgically excised at 1 h after pimonidazole hydrochloride injection. Tumor tissues were paraffin embedded, sectioned, and stained with FITC‐conjugated mouse anti‐pimonidazole protein adducts antibody (Hypoxyprobe Inc., HP1‐100 Kit; 1:100) and goat anti‐mouse CD31 antibody (Servicebio, GB13063; 1:100).…”