Simple preparation and purification of ethanol-free solutions of 3鈥?deoxy-3鈥?[¹⁸F]fluorothymidine by means of disposable solid-phase extraction cartridges

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• 作者：Claudio Pascali^a ; ^{claudio.pascali@istitutotumouri.mi.it} ; Anna Bogni^a ; Lorenza Fugazza^b ; Claudio Cucchi^a ; Ornella Crispu^c ; Luca Laera^a ; Ren Iwata^d ; Greta Maiocchi^a ; Flavio Crippa^a ; Emilio Bombardieri^a
• 关键词：[18F]FLT ; PET tracer ; Fluorothymidine ; SPE cartridge purification ; Automation
• 刊名：Nuclear Medicine and Biology
• 出版年：2012
• 期刊代码：43_09698051
• 类别：ph
• 出版时间：May, 2012
• 卷：39
• 期：4
• 页码：540-550
• 文件大小：839 K

摘要

Introduction

3鈥?Deoxy-3鈥?[¹⁸F]fluorothymidine ([¹⁸F]FLT) shows great potential as a tracer for proliferative studies with PET. However, its regular application is often limited by low radiochemical yields and the use of a troublesome HPLC separation. Moreover, a high content of ethanol, at least one-fold higher than the European Pharmacopoeia and US Pharmacopoeia's established limit, is always present in the final product. The present study reports an optimization of the reaction conditions and a simple and straightforward purification step which affords a solution of [¹⁸F]FLT suitable for human use.

Methods

Several conditions and materials were tested for both the nucleophilic substitution and purification step. The latter was achieved by means of a series of commercial solid-phase extraction cartridges. Very conveniently, the whole one-pot synthesis was carried out on commercial automated modules using basically the same setup employed for the synthesis of [¹⁸F]FDG.

Results

Under routine conditions, radiochemical yields of 37%[decay-corrected to start of synthesis (SOS)] were achieved in ca. 39 min from SOS, with radiochemical purities >98%(usually >99%). The negligible radiolysis observed could be easily suppressed by adding 0.5%of EtOH. Typical unlabelled chemical impurities detected were thymidine (0.15 ppm), thymine (0.28 ppm) and stavudine (0.05 ppm).

Conclusions

A reliable, simple and efficient preparation of [¹⁸F]FLT has been developed, able to afford an ethanol-free solution of the tracer with no need for any HPLC purification. Because of its similarity to the [¹⁸F]FDG synthesis, the method can be readily implemented on basically all the commercial modules developed for this common radiotracer.