[11C,127I] Altropane: A highly selective ligand for PET imaging of dopamine transporter sites

Cerebellar Vermis Involvement in Cocaine-Related Behaviors

“…Third, we were unable to detect specific [ 3 H]CFT binding in vermis lobule VIII suggesting some discrepancy between [ 3 H]CFT and both DAT-IR and [ 11 C]altropane labeling. As noted above, this discrepancy could be related to differential kinetics and pharmacological specificity for these ligands (Madras et al, 1998;Fischman et al, 2001) as well as from age and post-mortem reductions in functional DAT expression (Patel et al, 1993;Salvatore et al, 2003). Notwithstanding these limitations, we believe the present findings support the concept that the cerebellar vermis is involved in mediating cocaine-related behaviors.…”

“…While we (Kaufman et al, 1991;Fischman et al, 2001) and others documented low whole cerebellar DAT-binding levels in vitro and in vivo, as noted above, global DAT-binding measurements might have missed DAT-enriched zones. Thus, we conducted an in vitro autoradiographic study in human post-mortem cerebellar vermis tissue sections and an in vivo positron emission tomography (PET) study of healthy human cerebellum, using the DAT-selective cocaine congeners [ 3 H]2b-carbomethoxy-3b-(4-fluorophenyl) tropane ([ 3 H]CFT) (Kaufman et al, 1991) and [ 11 C]2b-carbomethoxy-3b-(4-fluorophenyl)-N-(1-iodoprop-1-en-3-yl) nortropane ([ 11 C]altropane) (Fischman et al, 2001) …”

Cerebellar Vermis Involvement in Cocaine-Related Behaviors

“…Third, we were unable to detect specific [ 3 H]CFT binding in vermis lobule VIII suggesting some discrepancy between [ 3 H]CFT and both DAT-IR and [ 11 C]altropane labeling. As noted above, this discrepancy could be related to differential kinetics and pharmacological specificity for these ligands (Madras et al, 1998;Fischman et al, 2001) as well as from age and post-mortem reductions in functional DAT expression (Patel et al, 1993;Salvatore et al, 2003). Notwithstanding these limitations, we believe the present findings support the concept that the cerebellar vermis is involved in mediating cocaine-related behaviors.…”

“…While we (Kaufman et al, 1991;Fischman et al, 2001) and others documented low whole cerebellar DAT-binding levels in vitro and in vivo, as noted above, global DAT-binding measurements might have missed DAT-enriched zones. Thus, we conducted an in vitro autoradiographic study in human post-mortem cerebellar vermis tissue sections and an in vivo positron emission tomography (PET) study of healthy human cerebellum, using the DAT-selective cocaine congeners [ 3 H]2b-carbomethoxy-3b-(4-fluorophenyl) tropane ([ 3 H]CFT) (Kaufman et al, 1991) and [ 11 C]2b-carbomethoxy-3b-(4-fluorophenyl)-N-(1-iodoprop-1-en-3-yl) nortropane ([ 11 C]altropane) (Fischman et al, 2001) …”

Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder

“…Notably, the only PET study reported reduced DAT availability in the putamen in a small MDD group (n = 9). In addition to showing a 28-fold selectivity for DAT over the serotonin transporter (vs 1:1 for [ 123 I]β-CIT and 3:1 for TRODAT), altropane accumulates within 30 minutes almost exclusively to DA-rich striatal regions, and the putamen:cerebellum ratio is 120:1, highlighting an exceptional degree of binding selectivity . We speculate that using this highly selective PET tracer allowed us to more reliably probe DAT function in unmedicated MDD.…”

VNTR polymorphism in the SLC6A3 gene does not influence dopamine transporter availability measured by [18F]FE-PE2I PET or [123I]FP-Cit SPECT

“…In particular, this was shown, when modeling the DAT-level with a mixed effect model where the average genotype effect was not significant. However, in the same model, the fixed effect of age [8]. A significant association between the 9R-allele and a higher DAT availability in the caudate compared to 10R-allele carriers was seen in healthy controls [18].…”

Cerebellar Vermis Involvement in Cocaine-Related Behaviors

“…Third, we were unable to detect specific [ 3 H]CFT binding in vermis lobule VIII suggesting some discrepancy between [ 3 H]CFT and both DAT-IR and [ 11 C]altropane labeling. As noted above, this discrepancy could be related to differential kinetics and pharmacological specificity for these ligands (Madras et al, 1998;Fischman et al, 2001) as well as from age and post-mortem reductions in functional DAT expression (Patel et al, 1993;Salvatore et al, 2003). Notwithstanding these limitations, we believe the present findings support the concept that the cerebellar vermis is involved in mediating cocaine-related behaviors.…”

“…While we (Kaufman et al, 1991;Fischman et al, 2001) and others documented low whole cerebellar DAT-binding levels in vitro and in vivo, as noted above, global DAT-binding measurements might have missed DAT-enriched zones. Thus, we conducted an in vitro autoradiographic study in human post-mortem cerebellar vermis tissue sections and an in vivo positron emission tomography (PET) study of healthy human cerebellum, using the DAT-selective cocaine congeners [ 3 H]2b-carbomethoxy-3b-(4-fluorophenyl) tropane ([ 3 H]CFT) (Kaufman et al, 1991) and [ 11 C]2b-carbomethoxy-3b-(4-fluorophenyl)-N-(1-iodoprop-1-en-3-yl) nortropane ([ 11 C]altropane) (Fischman et al, 2001) …”

Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder

“…Notably, the only PET study reported reduced DAT availability in the putamen in a small MDD group (n = 9). In addition to showing a 28-fold selectivity for DAT over the serotonin transporter (vs 1:1 for [ 123 I]β-CIT and 3:1 for TRODAT), altropane accumulates within 30 minutes almost exclusively to DA-rich striatal regions, and the putamen:cerebellum ratio is 120:1, highlighting an exceptional degree of binding selectivity . We speculate that using this highly selective PET tracer allowed us to more reliably probe DAT function in unmedicated MDD.…”

VNTR polymorphism in the SLC6A3 gene does not influence dopamine transporter availability measured by [18F]FE-PE2I PET or [123I]FP-Cit SPECT

“…In particular, this was shown, when modeling the DAT-level with a mixed effect model where the average genotype effect was not significant. However, in the same model, the fixed effect of age [8]. A significant association between the 9R-allele and a higher DAT availability in the caudate compared to 10R-allele carriers was seen in healthy controls [18].…”

Cerebellar Vermis Involvement in Cocaine-Related Behaviors

“…Third, we were unable to detect specific [ 3 H]CFT binding in vermis lobule VIII suggesting some discrepancy between [ 3 H]CFT and both DAT-IR and [ 11 C]altropane labeling. As noted above, this discrepancy could be related to differential kinetics and pharmacological specificity for these ligands (Madras et al, 1998;Fischman et al, 2001) as well as from age and post-mortem reductions in functional DAT expression (Patel et al, 1993;Salvatore et al, 2003). Notwithstanding these limitations, we believe the present findings support the concept that the cerebellar vermis is involved in mediating cocaine-related behaviors.…”

“…While we (Kaufman et al, 1991;Fischman et al, 2001) and others documented low whole cerebellar DAT-binding levels in vitro and in vivo, as noted above, global DAT-binding measurements might have missed DAT-enriched zones. Thus, we conducted an in vitro autoradiographic study in human post-mortem cerebellar vermis tissue sections and an in vivo positron emission tomography (PET) study of healthy human cerebellum, using the DAT-selective cocaine congeners [ 3 H]2b-carbomethoxy-3b-(4-fluorophenyl) tropane ([ 3 H]CFT) (Kaufman et al, 1991) and [ 11 C]2b-carbomethoxy-3b-(4-fluorophenyl)-N-(1-iodoprop-1-en-3-yl) nortropane ([ 11 C]altropane) (Fischman et al, 2001) …”

Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder

“…Notably, the only PET study reported reduced DAT availability in the putamen in a small MDD group (n = 9). In addition to showing a 28-fold selectivity for DAT over the serotonin transporter (vs 1:1 for [ 123 I]β-CIT and 3:1 for TRODAT), altropane accumulates within 30 minutes almost exclusively to DA-rich striatal regions, and the putamen:cerebellum ratio is 120:1, highlighting an exceptional degree of binding selectivity . We speculate that using this highly selective PET tracer allowed us to more reliably probe DAT function in unmedicated MDD.…”

VNTR polymorphism in the SLC6A3 gene does not influence dopamine transporter availability measured by [18F]FE-PE2I PET or [123I]FP-Cit SPECT

“…In particular, this was shown, when modeling the DAT-level with a mixed effect model where the average genotype effect was not significant. However, in the same model, the fixed effect of age [8]. A significant association between the 9R-allele and a higher DAT availability in the caudate compared to 10R-allele carriers was seen in healthy controls [18].…”