(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.
Erlandsson
Maria
M
Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, S-751 23 Uppsala, Sweden.
Karimi
Farhad
F
Lindhe
Orjan
O
Långström
Bengt
B
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