Abstract | UNLABELLED: 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 (64)Cu 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: (64)Cu-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 (64)Cu-DOTA-C-ANF is a promising candidate tracer for in vivo PET of NPR-Cs on atherosclerotic plaques.
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Authors | Yongjian Liu, Dana Abendschein, Geoffrey E Woodard, Raffaella Rossin, Kyle McCommis, Jie Zheng, Michael J Welch, Pamela K Woodard |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 51
Issue 1
Pg. 85-91
(Jan 2010)
ISSN: 1535-5667 [Electronic] United States |
PMID | 20008978
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- 64Cu-DOTA-C-type-atrial natriuretic factor
- Copper Radioisotopes
- Organometallic Compounds
- Radiopharmaceuticals
- gadofluorine
- Natriuretic Peptide, C-Type
- Atrial Natriuretic Factor
- Cholesterol
- Receptors, Atrial Natriuretic Factor
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Topics |
- Animals
- Atherosclerosis
(diagnostic imaging, pathology)
- Atrial Natriuretic Factor
- Cholesterol
(blood)
- Copper Radioisotopes
- Immunohistochemistry
- Isotope Labeling
- Magnetic Resonance Imaging
- Natriuretic Peptide, C-Type
(pharmacokinetics)
- Organometallic Compounds
- Positron-Emission Tomography
- Rabbits
- Radiopharmaceuticals
(chemical synthesis, pharmacokinetics)
- Receptors, Atrial Natriuretic Factor
(drug effects, metabolism)
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