Document Detail

Quantification of [11C]GB67 binding to cardiac alpha1-adrenoceptors with positron emission tomography: validation in pigs.
MedLine Citation:
PMID:  18481065     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: An increase in human cardiac alpha(1)-adrenoceptor (alpha(1)-AR) density is associated with various diseases such as myocardial ischemia, congestive heart failure, hypertrophic cardiomyopathy and hypertension. Positron emission tomography (PET) with an appropriate radioligand offers the possibility of imaging receptor function in the normal and diseased heart. [(11)C]GB67, an analogue of prazosin, has been shown in rats to have potential as a PET ligand with high selectivity to alpha(1)-AR. However, alpha(1)-AR density is up to ten times higher in rat heart compared to that in man. The aim of the present preclinical study was to extend the previous evaluation to a large mammal heart, where the alpha(1)-AR density is comparable to man, and to validate a method for quantification before PET studies in man.
METHODS: Seven [(11)C]GB67 PET studies, with weight-adjusted target dose of either 5.29 MBq kg(-1) (pilot, test-retest and baseline-predose studies) or 8.22 MBq kg(-1) (baseline-displacement studies), were performed in four anaesthetised pigs (39.5 +/- 3.9 kg). Total myocardial volume of distribution (V (T)) was estimated under different pharmacological conditions using compartmental analysis with a radiolabelled metabolite-corrected arterial plasma input function. A maximum possible blocking dose of 0.12 mumol kg(-1) of unlabeled GB67 was given 20 min before [(11)C]GB67 administration in the predose study and 45 min after administration of [(11)C]GB67 in the displacement study. In addition, [(15)O]CO (3,000 MBq) and [(15)O]H(2)O, with weight adjusted target dose of 10.57 MBq kg(-1), were also administered for estimation of blood volume recovery (RC) of the left ventricular cavity and myocardial perfusion (MBF), respectively.
RESULTS: [(11)C]GB67 V (T) values (in ml cm(-3)) were estimated to be 24.2 +/- 5.5 (range, 17.3-31.3), 10.1 (predose) and 11.6 (displacement). MBF did not differ within each pig, including between baseline and predose conditions. Predose and displacement studies showed that specific binding of [(11)C]GB67 to myocardial alpha(1)-ARs accounts for approximately 50% of V (T).
CONCLUSION: The present study offers a methodology for using [(11)C]GB67 as a radioligand to quantify human myocardial alpha(1)-ARs in clinical PET studies.
So-Jin Park-Holohan; Marie-Claude Asselin; David R Turton; Sharron L Williams; Susan P Hume; Paolo G Camici; Ornella E Rimoldi
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Publication Detail:
Type:  Journal Article; Validation Studies     Date:  2008-05-15
Journal Detail:
Title:  European journal of nuclear medicine and molecular imaging     Volume:  35     ISSN:  1619-7070     ISO Abbreviation:  Eur. J. Nucl. Med. Mol. Imaging     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-22     Completed Date:  2008-12-19     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  101140988     Medline TA:  Eur J Nucl Med Mol Imaging     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1624-35     Citation Subset:  IM    
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MeSH Terms
Arteries / metabolism
Carbon Monoxide / metabolism
Carbon Radioisotopes
Heart Ventricles / cytology,  metabolism
Myocardium / cytology,  metabolism*
Positron-Emission Tomography*
Prazosin / analogs & derivatives*,  blood,  metabolism*
Protein Binding
Receptors, Adrenergic, alpha-1 / metabolism*
Swine / metabolism*
Water / metabolism
Grant Support
MC_U120084164//Medical Research Council
Reg. No./Substance:
0/Carbon Radioisotopes; 0/N2-(6-((4-amino-6-7-dimethoxy-2-quinazolinyl)(methyl)amino)hexyl)-N2-methyl-2-furamide; 0/Receptors, Adrenergic, alpha-1; 059QF0KO0R/Water; 7U1EE4V452/Carbon Monoxide; XM03YJ541D/Prazosin

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