TY - JOUR
T1 - Molecular imaging of atherosclerotic plaque with 64Cu-labeled natriuretic peptide and PET
AU - Liu, Yongjian
AU - Abendschein, Dana
AU - Woodard, Geoffrey E.
AU - Rossin, Raffaella
AU - McCommis, Kyle
AU - Zheng, Jie
AU - Welch, Michael J.
AU - Woodard, Pamela K.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Cardiovascular disease is the leading cause of death worldwide. PET has the potential to provide information on the biology and metabolism of atherosclerotic plaques. Natriuretic peptides (NPs) have potent antiproliferative and antimigratory effects on vascular smooth-muscle cells (VSMCs) and, in atherosclerosis, participate in vascular remodeling, in which the expression of NP clearance receptors (NPR-Cs) is upregulated both in endothelium and in VSMCs. Methods: We investigated the potential of a C-type atrial natriuretic factor (C-ANF) to image developing plaque-like lesions in vivo. C-ANF was functionalized with 1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid (DOTA) and labeled with 64Cu for noninvasive PET in a hypercholesterolemic rabbit with atherosclerotic-like lesions induced by air desiccation of a femoral artery, followed by balloon overstretch of the developing neointima. Histopathology and immunohistochemistry were performed to assess plaque development and NPR-C localization. Results: 64Cu-DOTA- C-ANF uptake in the atherosclerotic region was visible on small-animal PET images, with the highest target-to-background ratio (3.59 ± 0.94) observed after the air desiccation-induced injury. Immunohistochemistry and immunofluorescence staining showed NPR-C near the luminal surface of the plaque and in VSMCs. PET and immunohistochemistry competitive blocking studies confirmed receptor-mediated tracer uptake in the plaque. With blocking, PET tracer localization of atherosclerotic to control arteries was decreased from 1.42 ± 0.02 to 1.06 ± 0.06 (P < 0.001). Conclusion: We demonstrated that 64Cu-DOTA-C-ANF is a promising candidate tracer for in vivo PET of NPR-Cs on atherosclerotic plaques.
AB - Cardiovascular disease is the leading cause of death worldwide. PET has the potential to provide information on the biology and metabolism of atherosclerotic plaques. Natriuretic peptides (NPs) have potent antiproliferative and antimigratory effects on vascular smooth-muscle cells (VSMCs) and, in atherosclerosis, participate in vascular remodeling, in which the expression of NP clearance receptors (NPR-Cs) is upregulated both in endothelium and in VSMCs. Methods: We investigated the potential of a C-type atrial natriuretic factor (C-ANF) to image developing plaque-like lesions in vivo. C-ANF was functionalized with 1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid (DOTA) and labeled with 64Cu for noninvasive PET in a hypercholesterolemic rabbit with atherosclerotic-like lesions induced by air desiccation of a femoral artery, followed by balloon overstretch of the developing neointima. Histopathology and immunohistochemistry were performed to assess plaque development and NPR-C localization. Results: 64Cu-DOTA- C-ANF uptake in the atherosclerotic region was visible on small-animal PET images, with the highest target-to-background ratio (3.59 ± 0.94) observed after the air desiccation-induced injury. Immunohistochemistry and immunofluorescence staining showed NPR-C near the luminal surface of the plaque and in VSMCs. PET and immunohistochemistry competitive blocking studies confirmed receptor-mediated tracer uptake in the plaque. With blocking, PET tracer localization of atherosclerotic to control arteries was decreased from 1.42 ± 0.02 to 1.06 ± 0.06 (P < 0.001). Conclusion: We demonstrated that 64Cu-DOTA-C-ANF is a promising candidate tracer for in vivo PET of NPR-Cs on atherosclerotic plaques.
KW - Atherosclerosis
KW - Natriuretic peptide
KW - PET
KW - Vascular targeting
UR - http://www.scopus.com/inward/record.url?scp=75149142267&partnerID=8YFLogxK
U2 - 10.2967/jnumed.109.066977
DO - 10.2967/jnumed.109.066977
M3 - Article
C2 - 20008978
AN - SCOPUS:75149142267
SN - 0161-5505
VL - 51
SP - 85
EP - 91
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 1
ER -