Radiosynthesis of a Novel PET Fluoronicotinamide for Melanoma Tumour PET Imaging; [18F]MEL050

Abstract

18 F]6-Fluoro-N-[2-(diethylamino)ethyl]nicotinamide [ 18 F]MEL050 is a novel nicotinamide-based radiotracer, designed to target random metastatic dissemination of melanoma tumours by targeting melanin. Preclinical studies suggest that [ 18 F]MEL050 has an excellent potential to improve diagnosis and staging of melanoma. Here we report the radiochemical optimization conditions of [ 18 F]MEL050 and its large scale automated synthesis using a GE FX FN automated radiosynthesis module for clinical, phase-1 investigation. [ 18 F]MEL050 was prepared via a one-step synthesis using no-carrier added K[ 18 F]F-Krytpofix Ò 222 (DMSO, 1708C, 5 min) followed by HPLC purification. Using 6-chloro-N-[2-(diethylamino)ethyl]nicotinamide as precursor, [ 18 F]MEL050 was obtained in 40-46% radiochemical yield (non-decay corrected), in greater than 99.9% radiochemical purity and specific activity ranging from 240 to 325 GBq mmol À1 . Total synthesis time including formulation was 40 min and [ 18 F]MEL050 was stable (99.8%) in PBS for 6 h.

[18F]Fluorination Optimisation and the Fully Automated Production of [18F]MEL050 Using a Microfluidic System

“…Initial reactions revealed that DMSO was the reaction solvent of choice in the synthesis of [ 18 F]1. Similarly to previous radiofluorination results for [ 18 F]1, [3] a concentration of 5 mg mL À1 of the precursor 2 was required to result in optimal RCY. Owing to the instrument requirements for precursor solution (,450 mL), the overall amount of 2 could be decreased to 3 mg in 600 mL of DMSO.…”

“…In recent years, our research group has reported the synthesis of numerous melanin-targeting [ 18 F]radiotracers, [2] including [ 18 F]MEL050 ([ 18 F]1), [3] which displays high tumour-to-body contrast ratio and rapid renal clearance. [4,5] Melanin is produced by melanocytes and is responsible for the pigmentation of skin and hair colour.…”

“…Parameters such as temperature, reaction time (referred to as residence time within flow reactors), and precursor concentration were varied to obtain the optimal radiofluorination conditions, which would be subsequently applied to the full production-scale experiment. [ 18 F] Radiolabelling was performed using a CH 3 (Fig. 1).…”

Marie Curie, Radioactivity, the Atom, the Neutron, and the Positron

“…Positrons are nowadays immensely important in positron emission tomography (see paper by Greguric et al [5] below). The fascinating story of the neutron -the Curie family's legacy -is reviewed expertly by John and Alsia White.…”

“…Ivan Greguric and coworkers describe a synthesis of positron-emitting 18 F-labelled nicotinamide (half-life of 18 F 110 min) designed to target random metastasis of melanoma tumours. [5] Because the ingestion of radionuclides is harmful and potentially lethal, it is of crucial importance to be able to determine their presence in drinking water -not least in Australia with its large deposits of uranium ore. Megan Cook and Ross Kleinsmith describe a method for the simultaneous determination of a-emitting Ra-226 and b-emitting Ra-228 in water by liquid scintillation spectrometry. [9] …”