One-pot radiosynthesis of [18F]FEDAC as a clinically applicable PET ligand for imaging TSPO
| Autor: | Kawamura, Kazunori, Kumata, Katsushi, Furutsuka, Kenji, Shiomi, Satoshi, Fujishiro, Tomoya, Ryuji, Watanabe, Takei, Makoto, Hashimoto, Hiroki, Ito, Takehito, Ogawa, Masanao, Igarashi, Nobuyuki, Muto, Masatoshi, Nengaki, Nobuki, Nemoto, Kazuyoshi, Zhang, Ming-Rong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Popis: | Objectives: Translocator protein (18 kDa) (TSPO), a nucleus-encoded mitochondrial target transmembrane protein, has been indicated as an active participant in the modulation of mitochondrial function. PET using radiolabeled TSPO probes has allowed non-invasive and reliable investigation of TSPO in neuropathological damages of experimental animals and humans. Many PET probes for TSPO imaging have been developed. Among them, [18F]FEDAC has potent binding affinity and selectivity for TSPO [1], high signal to neuroinflammation [2], and high sensitivity and specificity for detection of fatty liver diseases progression [3]. We had previously synthesized [18F]FEDAC by reaction of desmethyl-precursor with [18F]fluoroethyl bromide at two steps using a modified 18F-labelling synthesizer developed in our institute [1-3]. In this study, we simplified the synthesis of [18F]FEDAC by direct 18F-fluorination using a typical 18F-labelling synthesizer to transfer the preparation of [18F]FEDAC to other institutes toward multicenter clinical study. Methods: Tosylate-precursor for radiosynthesis of [18F]FEDAC was synthesized according to the procedures, as shown in Fig. 1. [18F]FEDAC was prepared by heating the tosylate-precursor with 18F- in DMSO at 110 ⁰C for 10-15 min. Results: Tosylate-precursor of [18F]FEDAC was successfully synthesized from desmethyl-precursor. [18F]FEDAC was obtained with sufficient radioactivity and suitable quality for injection in clinical application. The synthesis of [18 F]FEDAC was reproduceble to achieve >740 MBq, >300 GBq/μmol and >97% of radiochemical purity within 70 min of an overall synthesis time. All other analytical results were in compliance with our in-house quality control and assurance specifications. Conclusions: We successfully synthesized [18F]FEDAC by fluorination of the tosylate-precursor with 18F- using onepot 18F-labelling synthesizer. This radioligand will be used in clinical study. References: [1] Yanamoto K, et al (2009), Bioorg Med Chem Lett, 19, 1707-10. [2] Yui J, et al (2010), J Nucl Med, 51, 1301-9. [3] Xie L, et al (2012), J Hepatol, 57, 1076-82. 21st International Symposium on Radiopharmaceutical Sciences |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|