Document Detail


Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET.
MedLine Citation:
PMID:  24337599     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
METHODS: The distribution and stability of (18)F-FTC-146 in rats were assessed via PET/CT, autoradiography, γ counting, and high-performance liquid chromatography (HPLC). Preliminary PET/MRI of squirrel monkey brain was conducted along with HPLC assessment of (18)F-FTC-146 stability in monkey plasma and human serum.
RESULTS: Biodistribution studies showed that (18)F-FTC-146 accumulated in S1R-rich rat organs, including the lungs, pancreas, spleen, and brain. Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P < 0.001), suggesting radiotracer specificity for S1Rs. Similarly, PET/CT and autoradiography results demonstrated accumulation of (18)F-FTC-146 in rat brain regions known to contain S1Rs and that this uptake could be blocked by BD1047 pretreatment. Ex vivo analysis of (18)F-FTC-146 in the brain showed that only intact radiotracer was present at 15, 30, and 60 min, whereas rapid metabolism of residual (18)F-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism, whereas (18)F-FTC-146 appeared to be stable in human serum. Finally, liver microsome studies revealed that (18)F-FTC-146 has a longer half-life in human microsomes, compared with rodents.
CONCLUSION: Together, these results indicate that (18)F-FTC-146 is a promising tool for visualizing S1Rs in preclinical studies and that it has potential for mapping these sites in the human brain.
Authors:
Michelle L James; Bin Shen; Carsten H Nielsen; Deepak Behera; Christine L Buckmaster; Christophe Mesangeau; Cristina Zavaleta; Pradeep K Vuppala; Seshulatha Jamalapuram; Bonnie A Avery; David M Lyons; Christopher R McCurdy; Sandip Biswal; Sanjiv S Gambhir; Frederick T Chin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-12-12
Journal Detail:
Title:  Journal of nuclear medicine : official publication, Society of Nuclear Medicine     Volume:  55     ISSN:  1535-5667     ISO Abbreviation:  J. Nucl. Med.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-01-03     Completed Date:  2014-03-03     Revised Date:  2014-09-26    
Medline Journal Info:
Nlm Unique ID:  0217410     Medline TA:  J Nucl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  147-53     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Azepines / chemistry*,  diagnostic use*
Benzothiazoles / chemistry*,  diagnostic use*
Brain / pathology
Chromatography, High Pressure Liquid
Humans
Ligands
Magnetic Resonance Imaging
Male
Mice
Microsomes, Liver / metabolism
Positron-Emission Tomography*
Protein Binding
Radiopharmaceuticals / chemistry*
Rats
Rats, Sprague-Dawley
Receptors, sigma / chemistry*
Saimiri
Tissue Distribution
Tomography, X-Ray Computed
Grant Support
ID/Acronym/Agency:
P20 GM104932/GM/NIGMS NIH HHS; P20 GM104932/GM/NIGMS NIH HHS; P50 CA114747/CA/NCI NIH HHS; P50 CA114747/CA/NCI NIH HHS; P50 DA023205/DA/NIDA NIH HHS; R01 DA023205/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo(d)thiazol-2(3H)-one; 0/Azepines; 0/Benzothiazoles; 0/Ligands; 0/Radiopharmaceuticals; 0/Receptors, sigma; 0/sigma-1 receptor
Comments/Corrections

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