Striatal dopamine transporter imaging in nonhuman primates with iodine-123-IPT SPECT.
The regional distribution, kinetics and pharmacological specificity of a new radioiodinated cocaine analog, N-((E)-3-iodopropen-2-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl) tropane ([123I]IPT) were examined in brain SPECT studies (n = 20) of nonhuman primates.


METHODS
Radiolabeling and purification of the iododestannylated trialkyltin percursor yielded the tracer at greater than 90% radiochemical purity and high (> 20,000 Ci/mmole) specific activity. Cynomologous monkeys were injected with 7.2 +/- 1.3 mCi (mean +/- s.d.) of the tracer, and serial 10-min images were acquired (total scan time = 177 +/- 22 min). Images were reconstructed as transaxial slices (2 mm) using restorative techniques (Wiener prefiltering).


RESULTS
Radioactivity concentrated quickly in striatal regions (time of peak = 25 +/- 13 min) and cleared gradually thereafter (8.8 +/- 4.6% hr). Striatal-to-cerebellar ratios of 2.6 +/- 1.5 (n = 19), 6.7 +/- 3.2 (n = 20), 15.1 +/- 10.7 (n = 10) and 22.8 +/- 11.0 (n = 9) were observed at the time of peak and at 1, 2 and 3 hr p.i., respectively. In contrast, extrastriatal activity peaked earlier and at lower levels, cleared more rapidly and resembled cerebellar time-activity curves. Displacing doses of nonspecific antagonists of monoamine transporters (mazindol and beta-CIT) showed that 95% of specific [123I]IPT binding was reversible, while selective antagonists (e.g., paroxetine, nisoxetine and GBR 12909) demonstrated that striatal activity was specifically associated with dopamine transporters.


CONCLUSIONS
These results indicate that [123I]IPT is a useful radioligand for in vivo SPECT imaging of striatal dopamine transporters.
Malison
R T
RT
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA.
Vessotskie
J M
JM
Kung
M P
MP
McElgin
W
W
Romaniello
G
G
Kim
H J
HJ
Goodman
M M
MM
Kung
H F
HF
D000818:Animals; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000032:analysis*; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism; D004298:Dopamine / Q000032:analysis*; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008024:Ligands; D008252:Macaca fascicularis; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D014326:Tropanes; C087210:N-(3-iodopropen-1-yl)-2-carbomethoxy-3-(4-chlorophenyl)tropane; D004298:Dopamine