Fast enzymatic synthesis of n.c.a. 6‐[¹⁸F]fluorodopamine (FDA) from n.c.a. 6‐[¹⁸F]FDOPA and the fate of 6‐FDOPA and 6‐FDA in neuroblastoma and Caki‐1 cells after their uptake

Abstract

The catecholamine analogue [123I]mIBG has been used for scintigraphic imaging of neuroblastoma since 1984. It is taken up by the noradrenaline transporter (NAT), which is present in most neuroblastoma cells. An alternative imaging method could be PET with 6‐[18F]fluorodopamine, which is also taken up by NAT, but—in contrast to mIBG—also by dopamine transporter (DAT), present in neuroblastoma cells (NAT > DAT). An enzymatic method was established allowing a rapid, quantitative transformation of FDOPA to FDA by DOPA decarboxylase within 25 minutes. This strategy was applied to [18F]FDOPA, which was produced via nucleophilic synthesis (RCY 15%, 10 GBq, 50 GBq/μmol) and subsequently converted to [18F]FDA (RCY 35%‐50%, n = 5). Uptake and metabolism of FDOPA and FDA were analyzed in human Kelly and SK‐N‐SH neuroblastoma cell lines and in human Caki‐1 kidney cells that can take up catecholamines and mIBG via an organic cation transporter (OCT). FDOPA and FDA were taken up by all three cells, but FDOPA could only be converted to FDA in neuroblastoma cells. As today, [18F]FDOPA is well available in high yields, efficient enzymatic conversion to [18F]FDA to be used for NAT/DAT PET imaging in neuroendocrine tumors is an attractive, alternative synthesis route.

Neutral pH Formulation for 6-[18F]fluoro-ʟ-DOPA With High Radiochemical Stability

“…in the management of neuroendocrine tumors (NETs) [3][4][5]. Several [ 18 F]FDOPA synthesis reports with nucleophilic substitution methods have been developed to overcome the problems that arose with previous electrophilic substitution methods, such as non-regioselectivity, low radiochemical yields, and low molar activity [6][7][8][9][10][11][12][13][14]. Lemaire et al reported a general ve-step synthesis method using a speci c phase transfer catalyst (PTC) that yielded a su cient degree of enantiomeric purity and radiochemical yield to satisfy the recently adopted European Pharmacopeia (EP) speci cations [13,14].…”

Editorial for the special Issue “Jörg Steinbach”

“…Moreover, the development of cell and animal models for a detailed pharmacological radiotracer characterization of, eg, 11 C‐labeled azadipeptides, 18 F‐labeled benzylpiperazines or a cyclic uPA‐derived peptide for the urokinase‐type plasminogen activator receptor follows consistently.…”