当前位置： SCI文献检索 > EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING期刊下所有文献 > Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers.

Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers.

Abstract：

PURPOSE:Positron emission tomography (PET) imaging of serotonin 2A (5-HT(2A)) receptors with agonist tracers holds promise for the selective labelling of 5-HT(2A) receptors in their high-affinity state. We have previously validated [(11)C]Cimbi-5 and found that it is a 5-HT(2A) receptor agonist PET tracer. In an attempt to further optimize the target-to-background binding ratio, we modified the chemical structure of the phenethylamine backbone and carbon-11 labelling site of [(11)C]Cimbi-5 in different ways. Here, we present the in vivo validation of nine novel 5-HT(2A) receptor agonist PET tracers in the pig brain. METHODS:Each radiotracer was injected intravenously into anaesthetized Danish Landrace pigs, and the pigs were subsequently scanned for 90 min in a high-resolution research tomography scanner. To evaluate 5-HT(2A) receptor binding, cortical nondisplaceable binding potentials (BP(ND)) were calculated using the simplified reference tissue model with the cerebellum as a reference region. RESULTS:After intravenous injection, all compounds entered the brain and distributed preferentially into the cortical areas, in accordance with the known 5-HT(2A) receptor distribution. The largest target-to-background binding ratio was found for [(11)C]Cimbi-36 which also had a high brain uptake compared to its analogues. The cortical binding of [(11)C]Cimbi-36 was decreased by pretreatment with ketanserin, supporting 5-HT(2A) receptor selectivity in vivo. [(11)C]Cimbi-82 and [(11)C]Cimbi-21 showed lower cortical BP(ND), while [(11)C]Cimbi-27, [(11)C]Cimbi-29, [(11)C]Cimbi-31 and [(11)C]Cimbi-88 gave rise to cortical BP(ND) similar to that of [(11)C]Cimbi-5. CONCLUSION:[(11)C]Cimbi-36 is currently the most promising candidate for investigation of 5-HT(2A) receptor agonist binding in the living human brain with PET.

journal_name

Eur J Nucl Med Mol Imaging

journal_title

European journal of nuclear medicine and molecular imaging

authors

Ettrup A,Hansen M,Santini MA,Paine J,Gillings N,Palner M,Lehel S,Herth MM,Madsen J,Kristensen J,Begtrup M,Knudsen GM

doi

10.1007/s00259-010-1686-8

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

681-93

issue

4

eissn

1619-7070

issn

1619-7089

journal_volume

38

pub_type

杂志文章

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