Document Detail


Quantitation of CXCR4 expression in myocardial infarction using 99mTc-labeled SDF-1alpha.
MedLine Citation:
PMID:  18483105     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
METHODS: Recombinant SDF-1alpha was radiolabeled under aprotic conditions and purified by gel-filtration chromatography (GFC) using high-specific-activity 99mTc-S-acetylmercaptoacetyltriserine-N-hydroxysuccinimide ([99mTc-MAS3]-NHS) prepared by solid-phase preloading. Radiotracer stability and transmetallation under harsh conditions were quantified by GFC. Affinity, specificity, and maximum number of binding sites (Bmax) were quantified, with adenoviral-expressed CXCR4 on nonexpressing cells and endogenous receptor on rat neonatal cardiomyocytes, using a high-throughput live-cell-binding assay. Blood half-life, biodistribution, and clearance of intravenously injected [99mTc-MAS3]-SDF-1alpha were quantified in Sprague-Dawley rats before and after experimentally induced MI.
RESULTS: [99mTc-MAS3]-SDF-1alpha could be prepared in 2 h total with a specific activity of 8.0 x 10(7) MBq/mmol (2,166 Ci/mmol) and a radiochemical purity greater than 98%. Degradation of the radiotracer after boiling for 5 min, with and without 1 mM dithiothreitol, and transmetallation in 100% serum at 37 degrees C for 4 h were negligible. [99mTc-MAS3]-SDF-1alpha exhibits high specificity for CXCR4 on the surface of living rat neonatal cardiomyocytes, with an affinity of 2.7 +/- 0.9 nM and a Bmax of 4.8 x 10(4) binding sites per cell. After intravenous injection, 99mTc-labeled SDF-1alpha displays a blood half-life of 25.8 +/- 4.6 min, rapid renal clearance with only 26.2 +/- 6.1 percentage injected dose remaining in the carcass at 2 h, consistently low uptake in most organs (<0.1 percentage injected dose per gram), and no evidence of blood-brain barrier penetration. After MI was induced, CXCR4 expression levels in the myocardium increased more than 5-fold, as quantified using [99mTc-MAS3]-SDF-1alpha and confirmed using confocal immunofluorescence.
CONCLUSION: We describe a 99mTc-labeled SDF-1alpha radiotracer that can be used as a sensitive and specific probe for CXCR4 expression in vivo and demonstrate that this radiotracer is able to quantify changes in CXCR4 expression under different physiologic and pathologic states. Taken together, CXCR4 levels should now be quantifiable in vivo in a variety of animal model systems of human diseases.
Authors:
Preeti Misra; Djamel Lebeche; Hung Ly; Martina Schwarzkopf; George Diaz; Roger J Hajjar; Alison D Schecter; John V Frangioni
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-15
Journal Detail:
Title:  Journal of nuclear medicine : official publication, Society of Nuclear Medicine     Volume:  49     ISSN:  0161-5505     ISO Abbreviation:  J. Nucl. Med.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-30     Completed Date:  2008-07-28     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0217410     Medline TA:  J Nucl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  963-9     Citation Subset:  IM    
Affiliation:
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chemokine CXCL12 / diagnostic use*,  pharmacokinetics*
Gene Expression Profiling / methods
Heart / radionuclide imaging*
Male
Metabolic Clearance Rate
Myocardial Infarction / metabolism*,  radionuclide imaging*
Myocardium / metabolism*
Organ Specificity
Organotechnetium Compounds / diagnostic use*,  pharmacokinetics*
Radiopharmaceuticals / diagnostic use,  pharmacokinetics
Rats
Rats, Sprague-Dawley
Receptors, CXCR4 / metabolism*
Tissue Distribution
Grant Support
ID/Acronym/Agency:
R01 CA115296-05/CA/NCI NIH HHS; R01 HL073458-05/HL/NHLBI NIH HHS; R01 HL078691-04/HL/NHLBI NIH HHS; R01 HL088434/HL/NHLBI NIH HHS; R01 HL088434-03/HL/NHLBI NIH HHS; R01-CA-115296/CA/NCI NIH HHS; R01-HL-073458/HL/NHLBI NIH HHS; R01-HL-078691/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Chemokine CXCL12; 0/Cxcr4 protein, rat; 0/Organotechnetium Compounds; 0/Radiopharmaceuticals; 0/Receptors, CXCR4; 0/technetium 99m MAS3-SDF-1alpha
Comments/Corrections

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