Towards Optimal Automated 68Ga-Radiolabeling Conditions of the DOTA-Bisphosphonate BPAMD Without Pre-Purification of the Generator Eluate.

Abstract

DOTA-functionalized bisphosphonates can be useful tools for PET imaging of bone metastases when radiolabeled with ⁶⁸Ga. Moreover, the versatility of DOTA allows the complexation of radiometals with therapeutic applications (e.g., ¹⁷⁷Lu), positioning these bisphosphonates as attractive theranostic agents. Among these molecules, BPAMD is a compound whose radiolabeling with ⁶⁸Ga has already been described, but only through manual methods. Thus, a fully automated protocol for ⁶⁸Ga radiolabeling of BPAMD on the GAIA® ± LUNA® synthesis module was designed, and a thorough study of the radiolabeling conditions was undertaken. [⁶⁸Ga]Ga-BPAMD was produced in good radiochemical purity (> 93%) and high radiochemical yield (> 91%) using 0.3 M HEPES buffer. The nature of the reaction vessel showed no significant effect on the radiolabeling outcome. Similarly, addition of an antiradiolysis compound to the reaction medium did not significantly improve the already excellent stability of [⁶⁸Ga]Ga-BPAMD over time. The radiolabeled product obtained by automated synthesis was evaluated in vivo in healthy mice and confirmed high accumulation in the joints and along the backbone.