Radiolabeling and evaluation of 64+67Cu-2,2’-(1,2,4-Oxadiazole-3,5-diyl)di aniline as a theranostic agent for solid tumors

TL;DR

This study develops a new theranostic agent using copper isotopes for both imaging and treating solid tumors, showing promising tumor targeting and stability.

Contribution

A novel theranostic agent using 64+67Cu-ODDA is developed with high radiolabeling efficiency and tumor-targeting properties.

Findings

64+67Cu-ODDA achieved 97.0 ± 0.8% radiolabeling yield and remained stable in serum for five days.

The compound showed high tumor uptake in mice, peaking at 18.0 ± 0.3%ID/g at 2 hours post-injection.

Molecular docking revealed strong binding to EGFR and VEGFR2, suggesting potential anticancer activity.

Abstract

Copper-64 (64Cu) and Copper-67 (67Cu) are promising theranostic isotopes for PET imaging and targeted radiotherapy. In this study, 2,2’-(1,2,4-Oxadiazole-3,5-diyl)di aniline (ODDA) was successfully radiolabeled with 64+67Cu, achieving high radiolabeling yield (97.0 ± 0.8%) and excellent stability in serum over five days. The optimized radiolabeling conditions included a ligand concentration of 30 µg, pH 4, a reaction time of 15 min, and a temperature of 60 °C. The biodistribution study in Ehrlich ascites carcinoma-bearing mice showed an initial tumor uptake of 7.8 ± 0.4%ID/g at 0.5 h, peaking at 18.0 ± 0.3ID/g at 2 h, confirming selective tumor accumulation. The log P value of -0.8 indicated a hydrophilic nature, leading to predominant renal clearance. Molecular docking studies showed strong binding to EGFR (-9.1 kcal/mol) and VEGFR2 (-8.6 kcal/mol), suggesting potential anticancer activity.

Figures