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

Claudio Pascali, Anna Bogni, Lorenza Fugazza, Claudio Cucchi, Ornella Crispu, Luca Laera, Ren Iwata, Greta Maiocchi, Flavio Crippa, Emilio Bombardieri

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Introduction: 3'-Deoxy-3'-[ 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.

Original languageEnglish
Pages (from-to)540-550
Number of pages11
JournalNuclear Medicine and Biology
Volume39
Issue number4
DOIs
Publication statusPublished - May 2012

Fingerprint

Solid Phase Extraction
Pharmacopoeias
Ethanol
Fluorodeoxyglucose F18
High Pressure Liquid Chromatography
Stavudine
Thymine
Thymidine
alovudine

Keywords

  • [ F]FLT
  • Automation
  • Fluorothymidine
  • PET tracer
  • SPE cartridge purification

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Simple preparation and purification of ethanol-free solutions of 3'-deoxy-3'-[ 18F]fluorothymidine by means of disposable solid-phase extraction cartridges. / Pascali, Claudio; Bogni, Anna; Fugazza, Lorenza; Cucchi, Claudio; Crispu, Ornella; Laera, Luca; Iwata, Ren; Maiocchi, Greta; Crippa, Flavio; Bombardieri, Emilio.

In: Nuclear Medicine and Biology, Vol. 39, No. 4, 05.2012, p. 540-550.

Research output: Contribution to journalArticle

Pascali, Claudio ; Bogni, Anna ; Fugazza, Lorenza ; Cucchi, Claudio ; Crispu, Ornella ; Laera, Luca ; Iwata, Ren ; Maiocchi, Greta ; Crippa, Flavio ; Bombardieri, Emilio. / Simple preparation and purification of ethanol-free solutions of 3'-deoxy-3'-[ 18F]fluorothymidine by means of disposable solid-phase extraction cartridges. In: Nuclear Medicine and Biology. 2012 ; Vol. 39, No. 4. pp. 540-550.
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abstract = "Introduction: 3'-Deoxy-3'-[ 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.",
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AU - Pascali, Claudio

AU - Bogni, Anna

AU - Fugazza, Lorenza

AU - Cucchi, Claudio

AU - Crispu, Ornella

AU - Laera, Luca

AU - Iwata, Ren

AU - Maiocchi, Greta

AU - Crippa, Flavio

AU - Bombardieri, Emilio

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N2 - Introduction: 3'-Deoxy-3'-[ 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.

AB - Introduction: 3'-Deoxy-3'-[ 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.

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KW - PET tracer

KW - SPE cartridge purification

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