Synthesis and biodistribution of 99mTc-labeled piperidinyl bis(aminoethanethiol) complexes: potential brain perfusion imaging agents for single photon emission computed tomography.
In developing clinically useful 99mTc-labeled radiopharmaceuticals for the evaluation of regional cerebral perfusion with single photon emission computed tomography (SPECT), a number of substituted alkyl(aryl)piperidinyl bis(aminoethanethiol) ligands for chelating [99mTc]TcO(III) were synthesized. Each ligand forms two diastereomers, syn and anti, after reacting with a racemic mixture of the ligand. The diastereomers were separated by high-pressure liquid chromatography. In biodistribution studies conducted in rats, the diastereomers exhibit widely disparate brain uptake values; however, this disparity seems to diminish as the steric bulk of the substituent at the C-4 position of the piperidinyl moiety increases. Furthermore, all the complexes evaluated failed to show a prolonged retention in the rat brain, suggesting that further structural modification may be necessary to obtain clinically useful complexes from this class of compounds.
Efange
S M
SM
Department of Nuclear Medicine, State University of New York, Buffalo 14215.
Kung
H F
HF
Billings
J J
JJ
Blau
M
M
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002560:Cerebrovascular Circulation; D055598:Chemical Phenomena; D002621:Chemistry; D007275:Injections, Intravenous; D008024:Ligands; D008297:Male; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013667:Technetium; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D008024:Ligands; D010880:Piperidines; D013667:Technetium