Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM.
We studied the uptake, distribution, metabolism and washout of the dopamine D2 receptor ligand [123I]IBZM in healthy subjects (n = 12) with dynamic brain SPECT. The highest radioactivity level was detected in the striatum. Operationally-defined striatal "specific" uptake peaked at 69 min postinjection of radioligand and showed a gradual decline of 15% per hour thereafter. "Specific" uptake at maximal counts represented 53% of the total striatal radioactivity. Two subjects received haloperidol (20 micrograms/kg i.v.) 80 min postinjection of radioligand. Haloperidol caused a 2.6-fold increase in the rate of washout of specific striatal activity in comparison to that in the 10 control subjects and was consistent with drug-induced displacement of radioligand from the dopamine D2 receptor. Two classes of metabolites were detected in plasma and urine: a polar fraction, not extracted by ethyl acetate, and a nonpolar, extractable fraction consisting of parent compound and two compounds having shorter retention times on reversed-phase HPLC. Greater than half the plasma parent was metabolized within 10-15 min after administration. The volume of distribution, estimated from the peak arterial plasma concentration at 50-75 sec, was 7.7-10.2 l; the free (nonprotein bound) fraction of [123I]IBZM after in vitro incubation with blood or plasma was 4.4% +/- 0.4%. These results suggest that [123I]IBZM exhibits uptake in brain regions with high D2 receptor density and shows a relatively stable washout during which drugs affecting dopaminergic transmission may be administered.
Seibyl
J P
JP
Department of Psychiatry, Veterans Affairs Medical Center, Yale University School of Medicine, West Haven, Connecticut 06516.
Woods
S W
SW
Zoghbi
S S
SS
Baldwin
R M
RM
Dey
H M
HM
Goddard
A W
AW
Zea-Ponce
Y
Y
Zubal
G
G
Germine
M
M
Smith
E O
EO
D000328:Adult; D001549:Benzamides / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D003287:Contrast Media; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008297:Male; D011759:Pyrrolidines / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000032:analysis*; D015899:Tomography, Emission-Computed, Single-Photon
D001549:Benzamides; D003287:Contrast Media; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D006220:Haloperidol