Fully automated radiosynthesis of [⁶⁸Ga]Ga-FAPI-46 with cyclotron produced gallium

Radiopharmaceuticals capable of targeting the fibroblast activation protein have become widely utilized in the research realm as well as show great promise to be commercialized; with [⁶⁸Ga]Ga-FAPI-46 being one of the most widely utilized. Until now the synthesis has relied on generator-produced gallium-68. Here we present a developed method to utilize liquid-target cyclotron-produced gallium-68 to prepare [⁶⁸Ga]Ga-FAPI-46.

A fully-automated manufacturing process for [⁶⁸Ga]Ga-FAPI-46 was developed starting with the ⁶⁸Zn[p,n]⁶⁸Ga cyclotron bombardment to provide [⁶⁸Ga]GaCl₃, automated purification of the [⁶⁸Ga]GaCl₃, chelation with the precursor, and final formulation/purification. The activity levels produced were sufficient for multiple clinical research doses, and the final product met all release criteria. Furthermore, the process consistently provides < 2% of Ga-66 and Ga-67 at the 4-h expiry, meeting the Ph. Eur.

The automated radiosynthesis on the GE FASTlab 2 module purifies the cyclotron output into [⁶⁸Ga]GaCl₃, performs the labeling, formulates the product, and sterilizes the product while transferring to the final vial. Production of > 40 mCi (> 1480 MBq) of [⁶⁸Ga]Ga-FAPI-46 in excellent radiochemical yield was achieved with all batches meeting release criteria.