Validation of In-House Kit-Like Synthesis of 68 Ga-Trivehexin and Its Biodistribution for Targeting the Integrin αvβ6 Expressing Tumors

Abstract

Background:

Integrin αvβ6 has become an extremely promising theranostic target for precise delineation of fast-growing malignant cells in the recent years. The aim of the study was to validate the in-house kit-like synthesis of ⁶⁸Ga-Trivehexin (integrin αvβ6) and to evaluate its uptake in patients with integrin αvβ6 expressing head and neck and pancreatic cancer.

Materials and Methods:

⁶⁸Ga-Trivehexin was synthesized by adding the variable amount of integrin αvβ6 (30–50 μg) to full volume (4–5 mL) Ga-68 in 0.05 M HCl and heating the reaction mixture at 90°C for 12 min at pH 3.5–4 to obtain the radiotracer with high radiochemical purity (RCP) and high yield. Quality control procedures were done to assess the RCP, stability, pyrogenicity and sterility of the radiotracer. ⁶⁸Ga-Trivehexin was then administered in patients who met the eligibility criteria. Whole body PET/CT scans were done at variable time points post intravenous (i.v.) injection of 84–185 MBq of ⁶⁸Ga-Trivehexin to assess its biodistribution and maximum uptake time.

Results:

0.2 mCi of ⁶⁸Ga/μg of Trivehexin at 90°C for 12 min was the optimal parameter to obtain 85%–88% of noncorrected yield and 99% of RCP. The ⁶⁸Ga-Trivehexin showed in vitro stability upto 6 h and was also found to be sterile and pyrogen free. Intense radiotracer uptake was noticed in the tumor and no uptake was noticed in healthy tissues. PET/CT imaging at 60 min post injection was found to be the optimal time for imaging the tumors with ⁶⁸Ga-Trivehexin.

Conclusion:

The protocol for in-house kit-like labeling of ⁶⁸Ga-Trivehexin was safe, reproducible, and cost-effective. ⁶⁸Ga-Trivehexin is an extremely promising agent for noninvasive molecular imaging of integrin αvβ6 expressing tumors.