[Ga]/[Y]FAPI-46: Automated production and analytical validation of a theranostic pair.

INTRODUCTION

With respect to the broad application of FAPI-46 in therapy and diagnostics, there is a need for an efficient as well as convenient way for routine production and quality control of the theranostic pair [Y]Y/[Ga]Ga-FAPI-46, since no monograph is currently available for radiolabelled FAPI derivatives. The aim of the current work is to create a GMP compliant theranostic set up for the production and quality control of the diagnostic [Ga]Ga-FAPI-46 as well as the therapeutic drug [90 Y]Y-FAPI-46, which can be the basis for future monographic standards.

METHODS

Sterile [Y]yttrium chloride solution and a pharmaceutical grade Ge/Ga generator were applied for the labelling of FAPI-46 using the cassette based synthesis module Trasis EASYONE. All chemicals were GMP-grade and excipients were with marketing authorisation. The quality control included test procedures according to Ph. Eur.

RESULTS

Fully automated synthesis of the theranostic pair [Y]Y/[Ga]Ga-FAPI-46 was achieved on the Trasis EasyOne synthesizer with a radiochemical yield of 88 ± 7% and 56 ± 5% with a radiochemical purity of >99%. Stability experiments showed a durability for [Ga]Ga-FAPI-46 within 4 h and for [Y]Y-FAPI-46 within 24 h. All obtained specifications and validations were compliant with the European Pharmacopoeia and regulatory guidelines. Both products were successfully applied in cancer patients.

CONCLUSION

In the present work, efficient and robust procedures for the automated production and quality control of the theranostic pair [Ga]/[Y]FAPI 46 were developed and validated using the same synthetic platform. The described methods were evaluated in accordance with existing guidelines and toxicological limits, which can be a valuable basis for future monographic standards.