High yield production of [18F]AlF-FAPI-74 injection using an automated synthesizer for clinical research at Osaka University Hospital

Introduction: The fibroblast activation protein (FAP) has been shown to be highly expressed in the cancer associated fibroblasts of various cancers. [¹⁸F]AlF-FAPI-74 is a PET tracer that is highly selective and accumulates against FAP. We have already reported that [¹⁸F]AlF-FAPI-74 can be obtained with sufficient radioactivity and radiochemical purity using our established synthesis procedure with an automated synthesizer. This time, we reported that [¹⁸F]AlF-FAPI-74 injection was produced for human clinical research after confirming its quality and stability as an sterile injection in the three-lot tests.

Methods: The radio-synthesis of [¹⁸F]AlF-FAPI-74 using an automated synthesizer CFN-MPS200 made by Sumitomo was carried out according to the previous report (2). The FAPI-74 precursor and reference standard were provided from SOFIE.

10 mM phosphate buffered saline (pH 6.7) containing 100 mg sodium ascorbate was used as the formulation solvent for the purpose of preventing radiolysis, and filtration sterilization was performed using a 0.22-µm Millex-GV filter for sterile injection. In the filter after use, the bubble point value was measured using a filter integrity tester produced by Universal Giken. In the three-lot tests, [¹⁸F]AlF-FAPI-74 injection was confirmed the quality test items set in Table 1 and stability up to 6 hours. After approval by the Short-lived Radiopharmaceutical Safety Management Committee of Osaka University Hospital, 10 time syntheses of [¹⁸F]AlF-FAPI-74 injection were performed for human clinical research since June 2022.

Results: In the three-lot tests, the radioactivity of [¹⁸F]AlF-FAPI-74 was 9,983 ± 369 MBq and its concentration was 767 ± 28 MBq/mL at the end of synthesis (EOS) by the irradiation condition at 25 µA for 30 min. The radiochemical purity (RCP) was 97.6 ± 0.3 % at EOS and remained > 96.0 % after 6 hr of synthesis. AlF-FAPI-74 was 0.3 ± 0.1 µg/mL and sum of chemical impurities including AlF-FAPI-74 were 3.0 ± 0.1 µg/mL in the [¹⁸F]AlF-FAPI-74 injection. The bubble point value of the sterile filter was 340 ± 2 kPa, and sterility was confirmed for all samples. In addition, all other quality test items successfully passed the acceptance criteria. The following 10 syntheses for clinical application were all successful and [¹⁸F]AlF-FAPI-74 was obtained in an average radioactivity of 10.2 GBq. The produced [¹⁸F]AlF-FAPI-74 injection has already been administered to approximately 30 patients.

Conclusions: We produced [¹⁸F]AlF-FAPI-74 with an automated synthesizer with sufficient radioactivity and quality for human clinical research.

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