Automated and efficient radiosynthesis of [(18)F]FLT using a low amount of precursor.
Since 1991 until now, many radiosyntheses of [(18)F]FLT have been published. Most of them suffer from side reactions and/or difficult purification related to the large amount of precursor necessary for the labeling step. A fully automated synthesis using only commercial and unmodified materials with a reduced amount of precursor would be desirable.



We first explored the possibility to elute efficiently [(18)F]fluorine from commercial and unmodified cartridges with various amount of base. Based on these results, 10mg and 5mg of precursors were used for the fluorination step. The best conditions were transposed in an automated process for a one pot two steps synthesis of labeled FLT.



Using commercial and non-treated carbonate form of QMA cartridges, we were able to elute quantitatively the [(18)F]fluorine with a very low amount of base (0.59mg) and, with only 5mg of precursor, to perform an efficient fluorination reaction with up to 94% incorporation of [(18)F]fluorine. The synthesis was fully automated and radiochemical yields of 54% (decay corrected) were obtained within a synthesis time of 52minutes.



We demonstrate that a fully automated and efficient radiosynthesis of [(18)F]FLT is feasible with only 5mg of precursor. Compare to the present state of the art, our method provides high yields of pure [(18)F]FLT and is broadly adaptable to other synthesis automates.
Université de Strasbourg, IPHC, 23 rue du Loess, 67037 Strasbourg, France; CNRS, UMR 7178, 67037 Strasbourg, France. Electronic address: patrice.marchand@iphc.cnrs.fr.
Patrice
P
Marchand
Université de Strasbourg, IPHC, 23 rue du Loess, 67037 Strasbourg, France; CNRS, UMR 7178, 67037 Strasbourg, France. Electronic address: ali.ouadi@iphc.cnrs.fr.
Ali
A
Ouadi
Université de Strasbourg, IPHC, 23 rue du Loess, 67037 Strasbourg, France; CNRS, UMR 7178, 67037 Strasbourg, France. Electronic address: michel.pellicioli@iphc.cnrs.fr.
Michel
M
Pellicioli
Université de Strasbourg, IPHC, 23 rue du Loess, 67037 Strasbourg, France; CNRS, UMR 7178, 67037 Strasbourg, France. Electronic address: jacky.schuler@iphc.cnrs.fr.
Jacky
J
Schuler
Université de Strasbourg, IPHC, 23 rue du Loess, 67037 Strasbourg, France; CNRS, UMR 7178, 67037 Strasbourg, France. Electronic address: patrice.laquerriere@iphc.cnrs.fr.
Patrice
P
Laquerriere
Université de Strasbourg, IPHC, 23 rue du Loess, 67037 Strasbourg, France; CNRS, UMR 7178, 67037 Strasbourg, France. Electronic address: frederic.boisson@iphc.cnrs.fr.
Frédéric
F
Boisson
Université de Strasbourg, IPHC, 23 rue du Loess, 67037 Strasbourg, France; CNRS, UMR 7178, 67037 Strasbourg, France. Electronic address: david.brasse@iphc.cnrs.fr.
David
D
Brasse
D001331:Automation; D060326:Chemistry Techniques, Synthetic; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D011786:Quality Control; D011854:Radiochemistry / Q000379:methods*
D015224:Dideoxynucleosides; C002854:alovudine
Automated synthesis; FLT (3′-deoxy-3′-[(18)F]-fluoro-thymidine); Hindered alcohol; Preclinical