Quantitation of CXCR4 Expression in Myocardial Infarction Using 99mTc-Labeled SDF-1α

• DOI: 10.2967/jnumed.107.050054
• Publication Date: 2008-05-16T00:44:56Z
• Authors: Preeti Misra; Djamel Lebeche; Hung Ly; Martina Schwarzkopf; George Diaz; Roger J. Hajjar; Alison D. Schecter; John V. Frangioni
• Keywords: Biodistribution; Dithiothreitol

The chemokine stromal-derived factor-1alpha (SDF-1alpha, CXCL12) and its receptor CXCR4 are implicated as key mediators of hematopoietic stem cell retention, cancer metastasis, HIV infection. Their role in myocardial infarction (MI) is not well defined. noninvasive vivo quantitation expression central to understanding importance these diverse processes the cardiac response injury.Recombinant SDF-1alpha was radiolabeled under aprotic conditions purified by gel-filtration chromatography (GFC) using high-specific-activity 99mTc-S-acetylmercaptoacetyltriserine-N-hydroxysuccinimide ([99mTc-MAS3]-NHS) prepared solid-phase preloading. Radiotracer stability transmetallation harsh were quantified GFC. Affinity, specificity, maximum number binding sites (Bmax) quantified, with adenoviral-expressed on nonexpressing cells endogenous rat neonatal cardiomyocytes, a high-throughput live-cell-binding assay. Blood half-life, biodistribution, clearance intravenously injected [99mTc-MAS3]-SDF-1alpha Sprague-Dawley rats before after experimentally induced MI.[99mTc-MAS3]-SDF-1alpha could be 2 h total specific activity 8.0 x 10(7) MBq/mmol (2,166 Ci/mmol) radiochemical purity greater than 98%. Degradation radiotracer boiling for 5 min, without 1 mM dithiothreitol, 100% serum at 37 degrees C 4 negligible. exhibits high specificity surface living an affinity 2.7 +/- 0.9 nM Bmax 4.8 10(4) per cell. After intravenous injection, 99mTc-labeled displays blood half-life 25.8 4.6 rapid renal only 26.2 6.1 percentage dose remaining carcass h, consistently low uptake most organs (<0.1 gram), no evidence blood-brain barrier penetration. MI induced, levels myocardium increased more 5-fold, confirmed confocal immunofluorescence.We describe that can used sensitive probe demonstrate this able quantify changes different physiologic pathologic states. Taken together, should now quantifiable variety animal model systems human diseases.