Improved, one‐pot synthesis of 6‐[18F]fluorodopamine and quality control testing for use in patients with neuroblastoma. (22nd October 2018)

• Record Type: Journal Article
• Authors: Vāvere, Amy L.; Neumann, Kiel D.; Butch, Elizabeth R.; Hu, Bao; DiMagno, Stephen G.; Snyder, Scott E.
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 61:Number 14(2018)
• Page Start: 1069
• Page End: 1080
• Publication Date: 2018-10-22
• Subjects: 6‐[18F]fluorodopamine -- F‐DA -- fluorine‐18 -- neuroblastoma -- PET; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3685
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : 6‐[ 18 F]Fluorodopamine ([ 18 F]F‐DA) is taken into cells via the norepinephrine transporter (NET). Recent [ 18 F]F‐DA positron emission tomography–computed tomography (PET‐CT) imaging of adult neuroendocrine tumors shows a dramatic improvement in sensitivity over the standard‐of‐care, meta ‐iodobenzylguanidine (MIBG) single‐photon emission computed tomography (SPECT)–CT. A new precursor (ALPdopamine™) allows no‐carrier‐added synthesis resulting in high–molar activity [ 18 F]F‐DA. Automated synthesis of [ 18 F]F‐DA was performed in a single reactor using a two‐step procedure: 1) fluorination via thermolysis of a diaryliodonium salt precursor, followed by 2) acid hydrolysis. Phase transfer agents, Kryptofix 222 and two tetraalkylammonium salts, were investigated. Optimized synthesis of [ 18 F]F‐DA was achieved in 56 to 60 minutes (26% end of synthesis [EOS], nondecay corrected). The product passed all Food and Drug Administration (FDA)–required quality control testing for human use. Accumulation of [ 18 F]F‐DA in SK‐N‐BE(2)‐C (high NET expression) cells was significantly higher than in SH‐EP (minimal NET expression) cells ( P < 0.0001). ALPdopamine provides an effective scaffold for the routine production of [ 18 F]F‐DA for human use. Validation of uptake by neuroblastoma (NB) cell lines supports the use of [ 18 F]F‐DA for imaging NB patients. A pediatric NB imaging trial using [ 18 F]F‐DA PET has been approved (Investigational New Drug application (IND) no. 138638) based on the methods reported here. We expect [ 18 F]F‐DA will be localized in NB tumors and that high‐quality functional images will be obtained within minutes after injection. Abstract : An improved method for the nucleophilic synthesis of [18F]fluorodopamine, a highly promising PET radiopharmaceutical for imaging neuroendocrine tumors, is presented. The final product is demonstrated to meet established quality control requirements for human use. This optimized method is now in use for human subject research in patients with neuroblastoma.