title: Comparison of [123I]beta-CIT and [123I]IPCIT as single-photon emission tomography radiotracers for the dopamine transporter in nonhuman primates.
abstract: Single-photon emission tomographic (SPET) imaging with the radiotracer [123I]2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I]beta-CIT) has been reported to be a useful in vivo measure of dopamine (DA) transporters. However, in addition to its high DA transporter affinity, beta-CIT also binds with high affinity to serotonin (5-HT) transporters. 2 beta-Carboisopropoxy-3 beta-(4-iodophenyl)tropane (IPCIT) has been demonstrated by in vitro studies to have higher selectivity for the DA transporter. We compared [123I]beta-CIT and [123I]IPCIT SPET imaging and plasma metabolite analyses in baboons to evaluate the potential advantages of [123I]IPCIT for quantitative in vivo measurements of DA transporter densities. Both tracers had low levels (2% of total plasma 123I activity) of lipophilic radiolabeled metabolites at 420 min. [123I]IPCIT had significantly higher binding to plasma proteins. The average percent free (nonprotein bound) [123I]beta-CIT and [123I]IPCIT were 52% +/- 7% and 14% +/- 6%, respectively. Region of interest uptake data were normalized by injected dose and body weight. Consistent with the high density of 5-HT transporters in the midbrain and the lower 5-HT transporter affinity of IPCIT, the normalized peak specific midbrain uptake of [123I]beta-CIT (1.7 +/- 0.5) was higher than that of [123I]IPCIT (0.4 +/- 0.2). Consistent with its greater lipophilicity, [123I]IPCIT had higher nonspecific uptake, such that normalized cerebellar uptake of [123I]IPCIT was about twice that of [123I]beta-CIT. The ratio of specific to nonspecific uptake in striatum was greater for [123I]beta-CIT compared to [123I]IPCIT; however, striatal binding potentials and distribution volumes were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Yale University, West Haven, CT.
authors.forename: B E
authors.initials: BE
authors.lastname: Scanley
authors.forename: M S
authors.initials: MS
authors.lastname: al-Tikriti
authors.forename: M S
authors.initials: MS
authors.lastname: Gandelman
authors.forename: M
authors.initials: M
authors.lastname: Laruelle
authors.forename: Y
authors.initials: Y
authors.lastname: Zea-Ponce
authors.forename: R M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: S S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: P B
authors.initials: PB
authors.lastname: Hoffer
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
authors.forename: S
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000032:analysis; D003042:Cocaine / Q000031:analogs & derivatives*; D004298:Dopamine / Q000032:analysis; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins / Q000032:analysis; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010215:Papio; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000032:analysis; D050486:Serotonin Plasma Membrane Transport Proteins; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C079213:RTI 121; D012701:Serotonin; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D004298:Dopamine