Synthesis and in vitro evaluation of 18F-labelled di- and tri(ethylene glycol) metomidate esters
2009 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 52, no 7-8, 278-285 p.Article in journal (Refereed) Published
By replacing the alkyl chain in a metomidate ester with F-18-labelled di- or tri(ethylene glycol) chains, two F-18-labelled PET tracers, i.e. 2-(2-[F-18]fluoroethoxy)ethyl 1-[(1R)-1-phenylethyll-1 H-imidazole-5-carboxylate (1) and 2-[2-(2-[F-18]fluoroethoxy)-ethoxylethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (2), were synthesized. Two precursors, 2-(2-bromoethoxy)ethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate and 2-[2-(2-chloroethoxy)ethoxylethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate, were prepared and used in one-step nucleophilic [F-18]fluorination reactions using conventional and microwave heating. Organ distribution, frozen section autoradiography and metabolite analysis were performed. The decay-corrected radiochemical yields of 1 and 2 were 26 +/- 8 and 23 +/- 8%, respectively, when they were prepared using conventional heating. By performing microwave heating, the reaction time could be decreased and the yields of analogues 1 and 2 could be increased to 57 +/- 12 and 51 +/- 18%, respectively. Organ distribution studies in the rat showed considerable uptake in the lungs, adrenals and liver. Both compounds bound with low nonspecific binding (1: approx. 20-30%; 2: 2.9% or lower) to tissue from pig and human normal and pathologic adrenals. Metabolite analyses were performed in rats after 5 and 30 min for tracer 1 (20 +/- 6 and 2 +/- 1 %) and tracer 2 (27 +/- 5 and 6 +/- 4%). Both compounds are interesting candidates for the detection of different types of adrenal disorders.
Place, publisher, year, edition, pages
2009. Vol. 52, no 7-8, 278-285 p.
n.c.a. nucleophilic 18F-fluorination, di- and tri(ethylene glycol), metomidate, analogues
IdentifiersURN: urn:nbn:se:uu:diva-88794DOI: 10.1002/jlcr.1597ISI: 000268690300029OAI: oai:DiVA.org:uu-88794DiVA: diva2:159147