Synthesis and evaluation of radioiodinated 2-(2(RS)-aminopropyl)-5- iodothiophenes as brain imaging agents.
Methods have been developed for the preparation of 2-(2(RS)-aminopropyl)-5-iodothiophenes. The syntheses and physical properties of 2-(2(RS)-aminopropyl)-5-iodothiophene and N-isopropyl-2-(2(RS)-aminopropyl)-5-iodothiophene are described. The radioiodinated agents are of interest because of the high expected uptake and prolonged brain retention that may result from binding to high-capacity, relatively nonspecific amine binding sites. Radioiodine was introduced into the 5-position of 2-(2(RS)-aminopropyl)-5-iodothiophene and N-isopropyl-2-(2(RS)-aminopropyl)-5-iodothiophene by radioiodination of the corresponding 5-boronic acid or 5-(trimethylstannyl) derivatives. Tissue distribution studies in rats with 2-(2(RS)-aminopropyl)-5-[125I]iodothiophene showed high brain uptake (5 min, 2.77% dose/g; 30 min, 2.51% dose/g) and good brain/blood (B/B) ratios (5 min, 6/1; 30 min 3.8/1. A comparison of the brain uptake of the N-isopropyl derivative with the 2(RS)-aminopropyl analogue demonstrated higher initial brain uptake and brain to blood ratios (5 min, 3.2% dose/g; 10.3/1) but more rapid washout (30 min, 1.37% dose; 2.8/1). These data suggest that radiolabeled 2-(2(RS)-aminopropyl)-5-iodothiophenes are potentially useful agents for cerebral perfusion imaging by single-photon-emission computerized tomography (SPECT).
Goodman
M M
MM
Department of Radiology, University of Tennessee Medical Center, Knoxville.
Kabalka
G W
GW
Marks
R C
RC
Knapp
F F
FF
Lee
J
J
Liang
Y
Y
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D011877:Radionuclide Imaging; D051381:Rats; D011916:Rats, Inbred F344; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D013876:Thiophenes; C072402:2-(2-aminopropyl)-5-iodothiophene; C072403:N-isopropyl-2-(2-aminopropyl)-5-iodothiophene