TY - JOUR A1 - Wenz, Jan A1 - Arndt, Felix A1 - Samnick, Samuel T1 - A new concept for the production of \(^{11}\)C-labelled radiotracers JF - EJNMMI Radiopharmacy and Chemistry N2 - Background The GMP-compliant production of radiopharmaceuticals has been performed using disposable units (cassettes) with a dedicated synthesis module. To expand this “plug ‘n’ synthesize” principle to a broader scope of modules we developed a pressure controlled setup that offers an alternative to the usual stepper motor controlled rotary valves. The new concept was successfully applied to the synthesis of N-methyl-[\(^{11}\)C]choline, L-S-methyl-[\(^{11}\)C]methionine and [11C]acetate. Results The target gas purification of cyclotron produced [\(^{11}\)C]CO\(_2\) and subsequent conversion to [\(^{11}\)C]MeI was carried out on a TRACERlab Fx C Pro module. The labelling reactions were controlled with a TRACERlab Fx FE module. With the presented modular principle we were able to produce N-methyl-[\(^{11}\)C]choline and L-S-methyl-[\(^{11}\)C]methionine by loading a reaction loop with neat N,N'-dimethylaminoethanol (DMAE) or an ethanol/water mixture of NaOH and L-homocysteine (L-HC), respectively and a subsequent reaction with [\(^{11}\)C]MeI. After 18 min N-methyl-[\(^{11}\)C]choline was isolated with 52% decay corrected yield and a radiochemical purity of > 99%. For L-S-methyl-[\(^{11}\)C]methionine the total reaction time was 19 min reaction, yielding 25% of pure product (> 97%). The reactor design was used as an exemplary model for the technically challenging [\(^{11}\)C]acetate synthesis. The disposable unit was filled with 1 mL MeMgCl (0.75 M) in tetrahydrofuran (THF) bevore [\(^{11}\)C]CO\(_2\) was passed through. After complete release of [\(^{11}\)C]CO\(_2\) the reaction mixture was quenched with water and guided through a series of ion exchangers (H\(^+\), Ag\(^+\) and OH\(^−\)). The product was retained on a strong anion exchanger, washed with water and finally extracted with saline. The product mixture was acidified and degassed to separate excess [\(^{11}\)C]CO\(_2\) before dispensing. Under these conditions the total reaction time was 18 ± 2 min and pure [\(^{11}\)C]acetate (n = 10) was isolated with a decay corrected yield of 51 ± 5%. Conclusion Herein, we described a novel single use unit for the synthesis of carbon-11 labelled tracers for preclinical and clinical applications of N-methyl-[\(^{11}\)C]choline, L-S-methyl-[\(^{11}\)C]methionine and [11C]acetate. KW - carboxylation KW - methylation KW - Carbon-11 KW - isotopes KW - isotopic labelling KW - radiopharmaceuticals KW - radiochemistry Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300731 VL - 7 ER - TY - JOUR A1 - Lindner, Thomas A1 - Giesel, Frederik L. A1 - Kratochwil, Clemens A1 - Serfling, Sebastian E. T1 - Radioligands Targeting Fibroblast Activation Protein (FAP) JF - Cancers N2 - Simple Summary FAP-targeted radiotracers, recently introduced in cancer treatment, accumulate in Cancer-Associated Fibroblasts (CAFs). CAFs are present in tumor lesions but do not correspond to genuine cancer cells, although they behave in an abnormal and disease-promoting manner. One of their characteristic features, the expression of the surface protein FAP, can be utilized to discriminate between cancerous and healthy tissues. By the choice of an appropriate radionuclide, FAP-targeted tracers can be used for imaging or therapy in many cancer types. Therefore, the first successful application of FAP-targeted imaging has led to an enormous and growing interest in nuclear medicine and radiopharmacy. Abstract Targeting fibroblast activation protein (FAP) in cancer-associated fibroblasts (CAFs) has attracted significant attention in nuclear medicine. Since these cells are present in most cancerous tissues and FAP is rarely expressed in healthy tissues, anti-FAP tracers have a potential as pan-tumor agents. Compared to the standard tumor tracer [\(^{18}\)F]FDG, these tracers show better tumor-to-background ratios (TBR) in many indications. Unlike [\(^{18}\)F]FDG, FAP-targeted tracers do not require exhausting preparations, such as dietary restrictions on the part of the patient, and offer the possibility of radioligand therapy (RLT) in a theragnostic approach. Although a radiolabeled antibody was clinically investigated as early as the 1990s, the breakthrough event for FAP-targeting in nuclear medicine was the introduction and clinical application of the so-called FAPI-tracers in 2018. From then, the development and application of FAP-targeted tracers became hot topics for the radiopharmaceutical and nuclear medicine community, and attracted the interest of pharmaceutical companies. The aim of this review is to provide a comprehensive overview of the development of FAP-targeted radiopharmaceuticals and their application in nuclear medicine. KW - FAP KW - cancer associated fibroblasts KW - radiopharmaceuticals KW - drug discovery Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250121 SN - 2072-6694 VL - 13 IS - 22 ER -