[123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease.

Booij, Jan; Tissingh, Gerrit; Boer, G.J.; Speelman, Johannes D.; Stoof, Johannes C.; Janssen, A. G. M.; Wolters, Erik Ch.; Royen, E. A. Van

doi:10.1136/jnnp.62.2.133

Cited by 372 publications

(230 citation statements)

References 36 publications

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“…Jacobsen et al found a significant difference in striatal DAT binding of 13.4% in 30 healthy subjects (8). Van Dyck et al found a (18,19), and the binding ratios are much higher. All the other studies that demonstrated different effects of the VNTR on striatal DAT availability (10,11,13) (13).…”

Section: Discussionmentioning

confidence: 98%

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Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Giessen¹,

Win²,

Tanck³

et al. 2008

J Nucl Med

140

109

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Polymorphisms in the dopamine transporter (DAT) gene SLC6A3 are associated with human striatal DAT expression, but the exact effects on DAT expression are not clear. A variable number of tandem repeats (VNTR) in the 39 untranslated region of the DAT gene was previously investigated in relation to striatal DAT availability, but the results were inconclusive. Other polymorphisms in the DAT gene were not extensively studied. Therefore, we investigated whether polymorphisms in both 39 and 59 ends of the DAT gene show association with in vivo striatal DAT expression. Methods: The subjects were an ethnically homogeneous group of 79 healthy young adults. Striatal DAT availability was measured with 123 I-(2-b-carbomethoxy-3-b(4-iodophenyl)-tropane) ( 123 I-b-CIT) SPECT. The 40-base-pair VNTR in the 39 untranslated region of the DAT gene and the 2 single nucleotide polymorphisms (SNPs) rs2652511 and rs2937639 in the 59 end of the DAT gene were genotyped. Multiple-regression analysis was performed for each of the 3 polymorphisms. Analysis of the combination of the polymorphisms (haplotype analysis) was conducted for the triad rs2652511-rs2937639-VNTR. Results: For the VNTR, the 9-repeat (9R) allele was associated with significantly higher striatal DAT expression than was the 10-repeat (10R) allele (P 5 0.002). Subanalysis suggested a dominant effect for the 9R allele. Neither SNP rs2652511 nor SNP rs2937639 was associated with striatal DAT availability. The haplotype T-A-9R (rs2652511-rs2937639-VNTR) was significantly more associated with higher striatal DAT expression than were the other haplotypes (P 5 0.009). Conclusion: The DAT VNTR 9R carriers have higher striatal DAT availability than do 10R homozygotes. This finding replicates former studies that included healthy subjects and also used 123 I-b-CIT SPECT. Our haplotype analysis identified a subgroup of 9R carriers, the T-A-9R, which appears to be mainly responsible for the association with higher striatal DAT availability. Thus, a combination of polymorphisms in both the 39 and the 59 ends of the DAT gene is associated with in vivo striatal DAT expression. This finding in healthy subjects may contribute to research on DAT availability and genotype in neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 98%

“…Attenuation correction of all images was performed as described earlier (19). For quantification, a regionof-interest (ROI) analysis was performed.…”

Section: Spectmentioning

confidence: 99%

Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Giessen¹,

Win²,

Tanck³

et al. 2008

J Nucl Med

140

109

View full text Add to dashboard Cite

show abstract

“…Attenuation correction of all images was performed as described earlier (Booij et al, 1997). Images were reconstructed in 3D mode (http://www.neurophysics.com).…”

Section: Image Reconstruction and Analysismentioning

confidence: 99%

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

Win

Habraken

Reneman

et al. 2005

Neuropsychopharmacol

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“…In 2000, the radiotracer 123 I-N-v-fluoropropyl-2b-carboxymethoxy-3b-(4-iodophenyl)nortropane ( 123 I-FP-CIT) was registered in Europe to assess striatal dopamine transporter (DAT) binding, and it is now commonly used to study the integrity of nigrostriatal dopaminergic neurons in vivo (1). Recently, the same tracer was licensed in the United States.…”

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confidence: 99%

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with ¹²³I-FP-CIT SPECT in Healthy, Male Subjects

Koopman

Fleur²,

Fliers³

et al. 2012

J Nucl Med

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123 I-N-v-fluoropropyl-2b-carboxymethoxy-3b-(4-iodophenyl) nortropane ( 123 I-FP-CIT) is commonly used to assess the dopamine transporter in the striatum. However, recent studies suggest that this tracer may be used also to assess binding to monoamine transporters in the midbrain or diencephalon, which may reflect predominantly serotonin transporter (SERT) binding. However, it is still unclear at what time point after injection SPECT should be performed for optimal assessment of SERT with 123 I-FP-CIT. Therefore, we examined the time course of extrastriatal 123 I-FP-CIT binding. Methods: Nineteen healthy, male subjects were included, and SPECT images were acquired up to 3 h after 123 I-FP-CIT injection. Region-of-interest analysis was performed, and specific-to-nonspecific binding ratios were calculated. Results: Specific-to-nonspecific 123 I-FP-CIT binding ratios in the midbrain and diencephalon were significantly higher 2 h after injection than 1 h after injection and remained stable between 2 and 3 h after injection. Conclusion: The optimal time frame for assessing 123 I-FP-CIT binding to extrastriatal SERT is between 2 and 3 h after injection of the tracer. In 2000, the radiotracer 123 I-N-v-fluoropropyl-2b-carboxymethoxy-3b-(4-iodophenyl)nortropane ( 123 I-FP-CIT) was registered in Europe to assess striatal dopamine transporter (DAT) binding, and it is now commonly used to study the integrity of nigrostriatal dopaminergic neurons in vivo (1). Recently, the same tracer was licensed in the United States. The optimal time point for measuring striatal DAT is between 3 and 6 h after bolus injection of 123 I-FP-CIT (2).In vitro studies showed a high affinity of 123 I-FP-CIT for the DAT. However, this tracer also has a moderate affinity for the serotonin transporter (SERT) (3). Indeed, in healthy controls we showed that, after administration of the selective serotonin reuptake inhibitor paroxetine, 123 I-FP-CIT binding was significantly blocked in the SERT-rich midbrain and diencephalon (4). Likewise, another recent study showed that thalamic binding of 123 I-FP-CIT could be blocked by the selective serotonin reuptake inhibitor citalopram (5). The relative anatomic segregation between striatal DAT and extrastriatal SERT binding sets the condition for 123 I-FP-CIT SPECT studies to examine also SERT in vivo. Interestingly, recent clinical FP-CIT SPECT studies showed not only loss of striatal DAT but also loss of midbrain SERT binding in dementia with Lewy bodies and in Parkinson patients with depression (6,7). In these 2 studies, 123 I-FP-CIT binding in SERT-rich areas was measured 3 h after injection, but it is not known whether this time point is optimal for assessing FP-CIT binding to SERT.Abi-Dargham et al. studied 4 healthy controls and showed that peak specific 123 I-FP-CIT binding in the midbrain occurred at 72 6 37 min after injection, followed by slow washout (3). In a previous study, we measured SERT binding in the midbrain and diencephalon only at 1 and 3 h after injection of 123 I-FP-CIT (4). These preli...

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[123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease.

Cited by 372 publications

References 36 publications

Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with ¹²³I-FP-CIT SPECT in Healthy, Male Subjects

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[123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease.

Cited by 372 publications

References 36 publications

Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with 123I-FP-CIT SPECT in Healthy, Male Subjects

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Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with ¹²³I-FP-CIT SPECT in Healthy, Male Subjects