当前位置： SCI文献检索 > NUCLEAR MEDICINE AND BIOLOGY期刊下所有文献 > High-resolution imaging of brain 5-HT 1B receptors in the rhesus monkey using [11C]P943.

High-resolution imaging of brain 5-HT 1B receptors in the rhesus monkey using [11C]P943.

Abstract：

:The serotonin 5-HT(1B) receptors regulate the release of serotonin and are involved in various disease states, including depression and schizophrenia. The goal of the study was to evaluate a high affinity and high selectivity antagonist, [(11)C]P943, as a positron emission tomography (PET) tracer for imaging the 5-HT(1B) receptor. [(11)C]P943 was synthesized via N-methylation of the precursor with [(11)C]methyl iodide or [(11)C]methyl triflate using automated modules. The average radiochemical yield was approx. 10% with radiochemical purity of >99% and specific activity of 8.8+/-3.6 mCi/nmol at the end-of-synthesis (n=37). PET imaging was performed in non-human primates with a high-resolution research tomograph scanner with a bolus/infusion paradigm. Binding potential (BP(ND)) was calculated using the equilibrium ratios of regions to cerebellum. The tracer uptake was highest in the globus pallidus and occipital cortex, moderate in basal ganglia and thalamus, and lowest in the cerebellum, which is consistent with the known brain distribution of 5-HT(1B) receptors. Infusion of tracer at different specific activities (by adding various amount of unlabeled P943) reduced BP(ND) values in a dose-dependent manner, demonstrating the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg iv), a selective 5-HT(1B)/5-HT(1D) antagonist, resulted in reduction of BP(ND) values by 42-95% across regions; for an example, in occipital region from 0.71 to 0.03, indicating a complete blockade. These results demonstrate the saturability and specificity of [(11)C]P943 for 5-HT(1B) receptors, suggesting its suitability as a PET radiotracer for in vivo evaluations of the 5-HT(1B) receptor system in humans.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Nabulsi N,Huang Y,Weinzimmer D,Ropchan J,Frost JJ,McCarthy T,Carson RE,Ding YS

doi

10.1016/j.nucmedbio.2009.10.007

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

205-14

issue

2

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(09)00255-8

journal_volume

37

pub_type

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