(18)F-labelled metomidate analogues as adrenocortical imaging agents.
BACKGROUND
Two- and one-step syntheses of (18)F-labelled analogues of metomidate, such as 2-[(18)F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[(18)F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[(18)F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented.


METHODS
Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[(18)F]fluoroethyl 4-methylbenzenesulfonate or 3-[(18)F]fluoropropyl 4-methylbenzenesulfonate. These were used as (18)F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3.


RESULTS
The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46+/-3% and 79+/-30%, respectively.


CONCLUSIONS
Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.
Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, S-751 23 Uppsala, Sweden.
Maria
M
Erlandsson
Farhad
F
Karimi
Orjan
O
Lindhe
Bengt
B
Långström
D000302:Adrenal Cortex / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D005045:Etomidate / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D005629:Frozen Sections; D006801:Humans; D008297:Male; D008872:Microwaves; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; C084586:metomidate; D005045:Etomidate