Receptor binding characterization of the benzodiazepine radioligand 125I-Ro16-0154: potential probe for SPECT brain imaging.
The binding of an iodinated benzodiazepine (BZ) radioligand has been characterized, particularly in regard to its potential use as a neuroreceptor brain imaging agent with SPECT (Single Photon Emission Computed Tomography). Ro16-0154 is an iodine-containing BZ antagonist and a close analog of Ro15-1788. In tissue homogenates prepared from human and monkey brain, the binding of 125I-labeled Ro16-0154 was saturable, of high affinity (Kd = 0.5 nM at 37 degrees C), and had high ratios of specific to non-specific binding (approximately 40:1). Physiological concentrations of NaCl (150 mM) enhanced specific binding approximately 15% compared to buffer without this salt. Kinetic studies of association and dissociation demonstrated a temperature dependent decrease in affinity with increasing temperature. Drug displacement studies confirmed that 125I-Ro16-0154 binds to the "central" type BZ receptor: binding is virtually identical to that of 3H-Ro15-1788 except that 125I-Ro16-0154 shows an almost 10 fold higher affinity at 37 degrees C. These in vitro results suggest that 123I-labeled Ro16-0154 shows promise as a selective, high affinity SPECT probe of the brain's BZ receptor.
Johnson
E W
EW
VA Medical Center/116A, West Haven, CT.
Woods
S W
SW
Zoghbi
S
S
McBride
B J
BJ
Baldwin
R M
RM
Innis
R B
RB
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005442:Flumazenil / Q000378:metabolism / Q000031:analogs & derivatives; D006801:Humans; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D015899:Tomography, Emission-Computed, Single-Photon; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil; D012965:Sodium Chloride; D005680:gamma-Aminobutyric Acid; C063038:iomazenil