Reproducibility of iodine-123-beta-CIT SPECT brain measurement of dopamine transporters.
Iodine-123-beta-CIT has been used as a probe of monoamine transporters in human and nonhuman primates utilizing SPECT. To assess the utility of this tracer for measurement of striatal dopamine (DA) transporters in human disease, we studied the test/retest variability and reliability of SPECT measures obtained after bolus injection of [123I]beta-CIT 0-7 hr (Day 1) and 18-24 hr (Day 2) after administration.


METHODS
For the Day 2 study, seven healthy humans (4 men, 3 women; aged 19-74 yr) participated in two [123I]beta-CIT SPECT scans separated by 7-14 days. Subjects were imaged at 18, 21 and 24 hr postinjection of 370 MBq (10 mCi) [123I]beta-CIT. Two outcome measures were evaluated: (a) the ratio of specific striatal (activity associated with DA transporter binding) to nondisplaceable uptake, also designated V"3 and (b) the total, specific striatal uptake (%SSU) expressed as a percentage of injected radiotracer dose. Test/retest variability associated with V"3 and total specific striatal uptakes were compared for scans acquired at 18, 21 and 24 hr with 24 hr only postinjection scans. For the Day 1 study, three of the subjects participated in two kinetic studies of [123I]beta-CIT uptake. A three-compartment model was used for determination of konBmax and binding potential (BP = Bmax/Kd) and the reproducibility of the measures assessed.


RESULTS
In the Day 2 study, both outcome measures demonstrated excellent test/retest reproducibility with variability of V"3 = 6.8 +/- 6.8% and percent striatal uptake = 6.6 +/- 4.3% using data acquired from all time points. There were no significant differences in variability for the two outcome measures obtained. The intraclass correlation coefficient rho was 0.96 and 0.98 for V"3 and %SSU, respectively. Considering the 24 hr postinjection scans only, there was a nonsignificant trend toward lower test/retest variability for %SSU compared to V"3 (6.6 +/- 4.2% and 12.8 +/- 9.0%, respectively). The test/retest variability for the Day 1 kinetic modeling data showed marked differences depending on the fitting strategy and assumptions about the reversibility of [123I]beta-CIT in striatum. Using a model that assumed a low, fixed value for reversible striatal binding (k4) produced low variability (12 +/- 9%).


CONCLUSIONS
These data suggest that SPECT imaging performed at either 0-7 hr or 18-24 hr after [123I]beta-CIT injection permits calculation of reliable and reproducible measures of dopamine transporters and supports the feasibility of using [123I]beta-CIT in serial evaluation of human neuropsychiatric disease.
Seibyl
J P
JP
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Laruelle
M
M
van Dyck
C H
CH
Wallace
E
E
Baldwin
R M
RM
Zoghbi
S
S
Zea-Ponce
Y
Y
Neumeyer
J L
JL
Charney
D S
DS
Hoffer
P B
PB
Innis
R B
RB
D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000032:analysis*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D004298:Dopamine / Q000032:analysis*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D015203:Reproducibility of Results; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D004298:Dopamine