64Cu-1,4,7,10-Tetraazacyclododecane- N, N', N'', N'''-tetraacetic acid-C-type atrial natriuretic factor

Excerpt

The ⁶⁴Cu-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-C-type atrial natriuretic factor (C-ANF), abbreviated as ⁶⁴Cu-DOTA-C-ANF, is a positron emission tomography (PET) tracer that has been developed by Liu et al. for imaging atherosclerotic lesions by targeting natriuretic peptide clearance receptor (NPR-C) overexpressed on the surface of endothelial cells and vascular smooth muscle cells (VSMCs) in response to vascular injury (1). C-ANF is a fragment of C-type natriuretic peptide (CNP). The half-life of ⁶⁴Cu is 12.7 h (β⁺ = 17%, β^– = 40%).

The natriuretic peptides are a family of three structurally related but genetically distinct peptides (atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and CNP) (2, 3). These peptides exert their biological effects (natriuretic, diuretic, and vasodilating) by binding to three distinct natriuretic peptide receptors (NPRs): NPR-A, NPR-B, and NPR-C (4-6). CNP was originally isolated as a 22-amino-acid peptide from the porcine brain and has been found in human vascular endothelial cells, myocardium, kidneys, reproductive organs, and other tissues (7, 8). CNP preferentially binds to NPR-B, which is more abundant in veins than in arteries. Activation of the CNP/NPR-B pathway increases cyclic guanosine monophosphate (cGMP) in VSMCs and mediates vasorelaxation (2, 5). Some effects of the CNP are mediated by NPR-C, which is abundantly expressed in endothelial cells and in vessel neointima after arterial injury, where CNP/NPR-C signaling is implicated in an anti-proliferative action on VSMCs and endothelial cells (9, 10). CNP may also contribute to the anti-mitogenic and vasodilatory effects of ANP and BNP. However, CNP lacks significant natriuretic or diuretic effects (6).

Because of the findings that CNP/NPR-C is highly expressed in the vessel neointima and VSMCs at the sites of atherosclerotic plaques, Liu et al. investigated the potential of C-ANF to longitudinally image the progression of atherosclerosis in a rabbit model with PET (1). C-ANF was conjugated to DOTA and labeled with ⁶⁴Cu (⁶⁴Cu-DOTA-C-ANF). The results obtained by Liu et al. suggest that ⁶⁴Cu-DOTA-C-ANF is a promising candidate tracer for in vivo PET imaging of NPR-C on atherosclerotic plaques (1).