Fully-automated production of [68Ga]Ga-FAPI-46 for clinical application

Abstract

Background [68Ga]Ga-FAPI-46 is a promising radiopharmaceutical for in vivo detection of the fibroblast activation protein by positron emission tomography. Until now, the synthesis of [68Ga]Ga-FAPI-46 has been only performed manually. Our aim was to evaluate the automated synthesis of this radiopharmaceutical on two different commercially available synthesis modules in order to make the tracer readily available for clinical application. Results The synthesis of [68Ga]Ga-FAPI-46 with different amounts of precursor (10–50 μg) on the Modular Lab PharmTracer (MLPT) and Modular Lab eazy (ML eazy) from Eckert & Ziegler with a customized synthesis template and a customized single-use cassette yielded best results with 50 μg FAPI-46 for clinical multi-dose application. All relevant quality control parameters tested (e.g. sterility, stability and radiochemical purity) were in accordance with the European Pharmacopoeia. Conclusions [68Ga]Ga-FAPI-46 was successfully synthesized fully-automated on the synthesis modules Modular Lab PharmTracer and ML eazy and is, thus, available for multi-dose application in clinical settings.

FAPI-PET/CT in Cancer Imaging: A Potential Novel Molecule of the Century

“…With the development of 18 F production equipment and labeling technology, the advantages of 18 F clinical application will gradually increase: first, the maximum β + energy of 18 F is significantly lower than that of 68 Ga, so the sensitivity and spatial resolution of 18 F-PET imaging is better than 68 Ga-PET imaging, which can improve the image contrast to a certain extent; second, 68 Ga has become expensive due to a sharp increase in global demand and thus a shortage of supply ( 36 ); in addition, the 68 Ge/ 68 Ga generator is not yet capable for mass production of 68 Ga due to technical limitations, which means that the automated production of large quantities of FAPIs radiotracers is limited. In an automated synthesis study of 68 Ga-FAPI-46 by Spreckelmeyer et al., it was found that the radioactivity at the end of the synthesis was only 700–1,700 MBq, which was only sufficient for the examination of four to six patients ( 37 ). In comparison, the long half-life of 18 F (1.13 h) supports centralized commercial production and distribution to customers with no 18 F production facilities, resulting in a significant reduction in production costs ( 38 ).…”

Development and Validation of a PET/SPECT Radiopharmaceutical in Oncology

“…Morever, an automated synthesis minimizes risks of human error, adding to the reliability of the process and often allows production of higher doses, enabling more complex biological studies. With radiometals, where the labeling procedure is usually straightforward incubation method, handson syntheses are still very common, although small synthetic modules are available for preclinical development [8,9] and routinely used for human studies [10][11][12]. High activity yields (non-decay corrected) are of course desirable, but for 11 C-and 18 F-chemistry, a 3-4% activity yield from end-ofbombardment (EOB) to formulation is acceptable for initial validation.…”

New Fully Automated Preparation of High Apparent Molar Activity 68Ga-FAPI-46 on a Trasis AiO Platform

“…Varasteh et al prepared 68 Ga-FAPI-04 using a Scintomics GallElut + module to investigate the post-myocardial infarction (MI) fibroblast activation in a MI rat model [ 12 ]. Additionally, Spreckelmeyer et al evaluated the fully automated synthesis of 68 Ga-FAPI-46 for clinical applications on the commercially available Modular Lab PharmTracer and ML eazy modules [ 13 ].…”