[⁶⁸Ga]/[⁹⁰Y]FAPI-46: Automated production and analytical validation of a theranostic pair

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Good Manufacturing Practice (GMP)

Background:

• Fibroblast activation protein (FAP) targeting agents like FAPI-46 are crucial for cancer theranostics.
• Current limitations include the lack of established monographs for radiolabeled FAPI derivatives, hindering routine production and quality control.

Purpose of the Study:

• To establish a GMP-compliant automated synthesis and quality control framework for the theranostic pair [68Ga]Ga-FAPI-46 (diagnostic) and [90Y]Y-FAPI-46 (therapeutic).
• To provide a basis for future monographic standards for radiolabeled FAPI derivatives.

Main Methods:

• Automated synthesis of [68Ga]Ga-FAPI-46 and [90Y]Y-FAPI-46 using the Trasis EASYONE synthesizer with GMP-grade materials.
• Quality control adhering to European Pharmacopoeia (Ph. Eur.) standards.
• Stability studies for both diagnostic and therapeutic agents.

Main Results:

• High radiochemical yields (>99% purity) achieved for both [68Ga]Ga-FAPI-46 (88 ± 7%) and [90Y]Y-FAPI-46 (56 ± 5%).
• Demonstrated stability: [68Ga]Ga-FAPI-46 within 4 hours and [90Y]Y-FAPI-46 within 24 hours.
• All quality control specifications met European Pharmacopoeia and regulatory guidelines.
• Successful application in cancer patients.

Conclusions:

• Developed and validated efficient, robust automated procedures for producing and controlling [68Ga]/[90Y]FAPI-46.
• The validated methods, evaluated against guidelines and toxicological limits, can serve as a foundation for future monographic standards.
• The automated platform ensures consistent production of high-quality theranostic agents for clinical use.