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

Background: 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 [Ga-68]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 [Ga-68]Ga-FAPI-46.Results: A fully-automated manufacturing process for [Ga-68]Ga-FAPI-46 was developed starting with the Zn-68[p,n]Ga-68 cyclotron bombardment to provide [Ga-68]GaCl3, automated purification of the [Ga-68]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. standards.Conclusions: The automated radiosynthesis on the GE FASTlab 2 module purifies the cyclotron output into [Ga-68]GaCl3, performs the labeling, formulates the product, and sterilizes the product while transferring to the final vial. Production of > 40 mCi (> 1480 MBq) of [Ga-68]Ga-FAPI-46 in excellent radiochemical yield was achieved with all batches meeting release criteria.

Automated summary

The study presents a developed method to utilize liquid-target cyclotron-produced gallium-68 to prepare [Ga-68]Ga-FAPI-46. A fully-automated manufacturing process was developed, which successfully produced sufficient activity levels of [Ga-68]Ga-FAPI-46 for clinical research doses. The final product met all release criteria and the process consistently provided high radiochemical yield.