Optimization and scale-up of [68Ga]Ga-FAPI-46 production on a Modular-Lab PharmTracer platform for clinical application

IF 3.6 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2025-01-01 DOI:10.1016/j.nucmedbio.2024.108974

Irene Brusa , Veronica Serena Cabitza , Stefano Emiliani , Claudio Malizia , Emilia Fortunati , Lucia Zanoni , Giulia Cuzzani , Andrea Farolfi , Paolo Castellucci , Cristina Nanni , Stefano Fanti , Filippo Lodi

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引用次数: 0

Abstract

Background

Due to the increasing application of the fibroblast activation protein (FAP) targeting radiotracer [⁶⁸Ga]Ga-FAPI-46 in cancer diagnostics by PET/CT, there is a need for a convenient way for routine production of high activities of this tracer. The aim of the current work is the optimization and scale-up of an automated method for [⁶⁸Ga]Ga-FAPI-46 production on a PharmTracer module using two GalliaPharm generators.

Results

Several labeling conditions were evaluated and the best results were obtained with 40 μg of precursor, 3 mg ascorbic acid as anti-radiolysis agent, 0.4 M sodium acetate buffer pH 4.5 and 15 min heating at 95 °C. Furthermore, Vitamin C was added to the final formulation as stabilizer to ensure product quality in a time frame of 3 h after the end of synthesis. The evaluation of 43 routine syntheses of [⁶⁸Ga]Ga-FAPI-46 resulted in a decay-corrected yield of 91.1 ± 3.4 % and radiochemical purity of 99.8 ± 0.3 % as determined by radio-HPLC. All the quality control parameters were in accordance with specifications.

Conclusions

In conclusion, we developed an efficient and robust method able to provide multiple doses of [⁶⁸Ga]Ga-FAPI-46, enabling a better response to the clinical need for this radiopharmaceutical.

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来源期刊

Nuclear medicine and biology 医学-核医学

CiteScore

6.00

自引率

9.70%

发文量

479

审稿时长

51 days

期刊介绍： Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized. These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field. Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.