Structure-activity relationship of 99mTc complexes of phenylenediamine-thiol-thioether ligands (PhAT) to brain uptake in rats.
A novel class of ligands, phenylenediamine-thiol-thioether (PhAT), was synthesized, and their 99mTc complexes were evaluated for potential use as a functional brain imaging agent. The ligands reacted with Na99mTcO4 and SnCl2 to form single, stable, neutral, and lipophilic 99mTc complexes. Several of these complexes showed significant brain uptake and retention in rats. In particular, the S-ethyl, allyl, and propargyl derivatives had high initial brain uptake (0.88, 0.99, and 0.82% dose/g at 5 min, respectively) and good retention (0.71, 0.75, and 0.67% dose/g at 30 min). The structure-activity relationship of alkyl, alkenyl, and alkynyl thioether derivatives is reported.
McBride
B J
BJ
Research and Development Laboratory, Medi-Physics, Inc., Emeryville, California 94608.
Baldwin
R M
RM
Kerr
J M
JM
Wu
J L
JL
Schultze
L M
LM
Salazar
N E
NE
Chinitz
J M
JM
Byrne
E F
EF
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008024:Ligands; D010655:Phenylenediamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013667:Technetium / Q000378:metabolism*; D014018:Tissue Distribution
D008024:Ligands; D010655:Phenylenediamines; D013440:Sulfides; D013667:Technetium