Improved, one‐pot synthesis of 6‐[18F]fluorodopamine and quality control testing for use in patients with neuroblastoma
- 22 October 2018
- journal article
- research article
- Published by Wiley in Journal of Labelled Compounds and Radiopharmaceuticals
- Vol. 61 (14) , 1069-1080
Abstract
6‐[18F]Fluorodopamine ([18F]F‐DA) is taken into cells via the norepinephrine transporter (NET). Recent [18F]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 [18F]F‐DA. Automated synthesis of [18F]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 [18F]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 [18F]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 [18F]F‐DA for human use. Validation of uptake by neuroblastoma (NB) cell lines supports the use of [18F]F‐DA for imaging NB patients. A pediatric NB imaging trial using [18F]F‐DA PET has been approved (Investigational New Drug application (IND) no. 138638) based on the methods reported here. We expect [18F]F‐DA will be localized in NB tumors and that high‐quality functional images will be obtained within minutes after injection.Keywords
Funding Information
- Hartwell Foundation
- National Institute of Biomedical Imaging and Bioengineering (R01 EB013713-01A1, R01EB015536)
- American Lebanese Syrian Associated Charities
This publication has 28 references indexed in Scilit:
- Evaluation of tetraethylammonium bicarbonate as a phase-transfer agent in the formation of [18F]fluoroarenesJournal of Fluorine Chemistry, 2012
- Vorinostat Increases Expression of Functional Norepinephrine Transporter in Neuroblastoma In Vitro and In Vivo Model SystemsClinical Cancer Research, 2011
- The origin of neuroendocrine tumors and the neural crest sagaLaboratory Investigation, 2011
- New imaging approaches to phaeochromocytomas and paragangliomasClinical Endocrinology, 2010
- Comparison of 18F-Fluoro-L-DOPA, 18F-Fluoro-Deoxyglucose, and 18F-Fluorodopamine PET and 123I-MIBG Scintigraphy in the Localization of Pheochromocytoma and ParagangliomaThe Journal of Clinical Endocrinology & Metabolism, 2009
- Three-Step, “One-Pot” Radiosynthesis of 6-Fluoro-3,4-Dihydroxy-l-Phenylalanine by Isotopic ExchangeJournal of Nuclear Medicine, 2009
- The role of 6-[18F]fluorodopamine positron emission tomography in the localization of adrenal pheochromocytoma associated with von Hippel–Lindau syndromeEuropean Journal of Endocrinology, 2007
- A color spot test for the detection of Kryptofix 2.2.2 in [18F]FDG preparationsNuclear Medicine and Biology, 1997
- Metabolic Fate of the Sympathoneural Imaging Agent 6-[18F]Fluorodopamine in HumansClinical and Experimental Hypertension, 1997
- Rapid, regiospecific syntheses of deuterium substituted 6‐[18F]fluorodopamine (α,α‐D2; β,β‐D2 and α,α,β,β‐D4) for mechanistic studies with positron emission tomographyJournal of Labelled Compounds and Radiopharmaceuticals, 1993