J Nucl Med. 2007; 48 (Supplement 2):103P
Cardiovascular: Basic Science
Plaque Imaging |
64Cu-labeled natriuretic peptide: A promising tracer for atherosclerotic plaque molecular imaging with PET
Raffaella Rossin1,
Dana Abendschein2,
Jie Zheng1,
Terry Sharp1,
Geoffrey Woodard3,
Paul McQuade1,
Michael Welch1 and
Pamela Woodard1
1 Mallinckrodt Institute of Radiology; ;
2 Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; ;
3 NIH/NIAID, Bethesda, Maryland
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Objectives: Molecular imaging of vulnerable atherosclerotic lesions is of paramount importance for the identification of patients at risk for thrombo-ischemic event. Recently, the role of natriuretic peptides (NPs) in the pathogenesis of coronary atherosclerotic plaque was suggested, as these cardiac hormones have potent anti-proliferative and anti-migratory effects on vascular smooth muscle cells. Here, we investigate the use of a 64Cu-labeled NP fragment as a possible tool for non-invasive plaque imaging with PET. Methods: C-ANF (atrial natriuretic factor), a C-type NP analog, was functionalized with DOTA and labeled with 64Cu in 0.1M citrate buffer (pH 5.5). After DTPA challenge and Sep-Pak C-18 purification, the radiochemical purity of 64Cu-DOTA-ANF was >95%, as measured by radio-HPLC. The right femoral artery of male New Zealand white rabbits fed a cholesterol-rich diet was double-injured by air dessication and balloon overstretching. The presence of atherosclerotic lesion was confirmed by 3T MRI 1 hr after administration of a plaque-targeted contrast agent (Gadoflurine M, Schering AG). A rabbit was injected with 64Cu-DOTA-ANF (2.8 mCi, ca. 7.5 µg peptide) and a 20 min dynamic scan was acquired on the microPET Focus-220. Fiducial markers attached to the animal bed and filled with a 64Cu aqueous solution were used to correlate the MRI and microPET images. Histopathologic imaging and immunohistochemistry (IHC) of the ex-vivo atherosclerotic artery were performed. Results: IHC demonstrated the presence of NP receptor type-C. MicroPET images clearly showed tracer accumulation at the injury site, with an average SUV of 2.1 during the acquisition scan (3-fold higher than surrounding muscle). In the same time frame, the uninjured control artery was not observable. Conclusions: This preliminary imaging study suggests that 64Cu-DOTA-ANF is a promising candidate tracer for PET imaging of atherosclerotic plaques.
Research Support (if any): This work is supported by the NIH as a Program of Excellence in Nanotechnology (HL080729). The production of 64Cu is supported by a NCI grant (CA86307).
