Automated Radiochemical Synthesis of [18F]FBEM: a Thiol Reactive Synthon for Radiofluorination of Peptides and Proteins

Overview

Journal Appl Radiat Isot

Specialties Environmental Health
Nuclear Medicine

Date 2010 Oct 23

PMID 20965741

Citations 31

Authors

Dale O Kiesewetter

Orit Jacobson

Lixin Lang

Xiaoyuan Chen

Affiliations

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Abstract

The automated radiochemical synthesis of N-[2-(4-[(18)F]fluorobenzamido)ethyl]maleimide ([(18)F]FBEM, IUPAC name: N-maleoylethyl-4-[(18)F]fluorobenzamide), a prosthetic group for radiolabeling the free sulfhydryl groups of peptides and proteins, is herein described. 4-[(18)F]fluorobenzoic acid was first prepared by nucleophilic displacement of a trimethylammonium moiety on a pentamethylbenzyl benzoate ester with [(18)F]fluoride. In the second step the ester was cleaved under acidic conditions. Finally, 4-[(18)F]fluorobenzoic acid was coupled to N-(2-aminoethyl)maleimide using diethylcyanophosphate and diisopropylethyl amine. Following high-performance liquid chromatography (HPLC) purification, [(18)F]FBEM was obtained in 17.3±7.1% yield (not decay corrected) in approximately 95 min. Isolation from the HPLC eluate and preparation for subsequent use, which was conducted manually, required an additional 10-15 min. The measured specific activity for three batches was 181.3, 251.6, and 351.5 GBq/μmol at the end of bombardment (EOB).

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References

Becaud J, Mu L, Karramkam M, Schubiger P, Ametamey S, Graham K . Direct one-step 18F-labeling of peptides via nucleophilic aromatic substitution. Bioconjug Chem. 2009; 20(12):2254-61. DOI: 10.1021/bc900240z. View

de Bruin B, Kuhnast B, Hinnen F, Yaouancq L, Amessou M, Johannes L . 1-[3-(2-[18F]fluoropyridin-3-yloxy)propyl]pyrrole-2,5-dione: design, synthesis, and radiosynthesis of a new [18F]fluoropyridine-based maleimide reagent for the labeling of peptides and proteins. Bioconjug Chem. 2005; 16(2):406-20. DOI: 10.1021/bc0497463. View

Wuest F, Berndt M, Bergmann R, van den Hoff J, Pietzsch J . Synthesis and application of [18F]FDG-maleimidehexyloxime ([18F]FDG-MHO): a [18F]FDG-based prosthetic group for the chemoselective 18F-labeling of peptides and proteins. Bioconjug Chem. 2008; 19(6):1202-10. DOI: 10.1021/bc8000112. View

Kiesewetter D, Kramer-Marek G, Ma Y, Capala J . Radiolabeling of HER2 specific Affibody(R) molecule with F-18. J Fluor Chem. 2009; 129(9):799-805. PMC: 2630254. DOI: 10.1016/j.jfluchem.2008.06.021. View

Kiesewetter D, Jagoda E, Kao C, Ma Y, Ravasi L, Shimoji K . Fluoro-, bromo-, and iodopaclitaxel derivatives: synthesis and biological evaluation. Nucl Med Biol. 2002; 30(1):11-24. DOI: 10.1016/s0969-8051(02)00351-7. View

Lang L, Jagoda E, Schmall B, Vuong B, Adams H, Nelson D . Development of fluorine-18-labeled 5-HT1A antagonists. J Med Chem. 1999; 42(9):1576-86. DOI: 10.1021/jm980456f. View

Berndt M, Pietzsch J, Wuest F . Labeling of low-density lipoproteins using the 18F-labeled thiol-reactive reagent N-[6-(4-[18F]fluorobenzylidene)aminooxyhexyl]maleimide. Nucl Med Biol. 2007; 34(1):5-15. DOI: 10.1016/j.nucmedbio.2006.09.009. View

Vaidyanathan G, Zalutsky M . Synthesis of N-succinimidyl 4-[18F]fluorobenzoate, an agent for labeling proteins and peptides with 18F. Nat Protoc. 2007; 1(4):1655-61. DOI: 10.1038/nprot.2006.264. View

Toyokuni T, Walsh J, Dominguez A, Phelps M, Barrio J, Gambhir S . Synthesis of a new heterobifunctional linker, N-[4-(aminooxy)butyl]maleimide, for facile access to a thiol-reactive 18F-labeling agent. Bioconjug Chem. 2003; 14(6):1253-9. DOI: 10.1021/bc034107y. View

10.

Kalen J, Hirsch J, Kurdziel K, Eckelman W, Kiesewetter D . Automated synthesis of 18F analogue of paclitaxel (PAC): [18F]Paclitaxel (FPAC). Appl Radiat Isot. 2006; 65(6):696-700. PMC: 1904428. DOI: 10.1016/j.apradiso.2006.10.015. View

11.

Cai W, Zhang X, Wu Y, Chen X . A thiol-reactive 18F-labeling agent, N-[2-(4-18F-fluorobenzamido)ethyl]maleimide, and synthesis of RGD peptide-based tracer for PET imaging of alpha v beta 3 integrin expression. J Nucl Med. 2006; 47(7):1172-80. PMC: 1704081. View

12.

Ogawa M, Hatano K, Oishi S, Kawasumi Y, Fujii N, Kawaguchi M . Direct electrophilic radiofluorination of a cyclic RGD peptide for in vivo alpha(v)beta3 integrin related tumor imaging. Nucl Med Biol. 2002; 30(1):1-9. DOI: 10.1016/s0969-8051(02)00387-6. View