99mTc-Labeled SDF as a target-specific molecular probe for noninvasive imaging of myocardial infarction

MEDI 269

Preeti Misra, pmisra@bidmc.harvard.edu1, Alison D Schecter2, Djamel Lebeche3, Hung Ly3, Roger J Hajjar3, and John V. Frangioni4. (1) Haematology/Oncology, Beth Israel Deaconess medical Center, Harvard Medical school, 330 Brookline Ave, SLB-05, Boston, MA 02215, (2) Department of Medicine and Immunobiology, Mount Sinai School of Medicine, One Gustave levy place, New York, NY 10029, (3) Cardiovascular Research Center, Mount Sinai School of Medicine, One Gustave levy place, Box 1030, New York, NY 10029, (4) Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215
Stromal-Cell-Derived Factor 1 (SDF-1) and its chemokine receptor CXCR4 have been proposed as key mediators of cardiac physiology. To image CXCR4 expression in vivo, we have synthesized 99mTc-SDF in one-step, using solid-phase preparation of the reactive intermediate [99mTc-MAS3]-NHS. The specific activity of [99mTc-MAS3]-SDF was 1086 Ci/mmol. Affinity for adenovirus-expressing CXCR4-positive cells was 1.85 ± 0.15 nM, with a BMax of 2.6 x 105 receptors per cell. For neonatal rat cardiomyocytes affinity was 2.9 ± 0.1 nM, with a BMax of 4.8x 104. After intravenous injection, blood clearance was rapid via the kidneys. Rats with induced myocardial infarctions had uptake of 0.57 ± 0.07 %ID/g in injured myocardium vs. 0.11 ± 0.01 %ID/g in non-injured myocardium. In conclusion, solid-phase chemical strategies for [99mTc-MAS3-NHS] pre-loading permit one-step preparation of disease-targeting radiotracers, which in turn, can be used to study important physiologic/pathologic processes in vivo.
 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007