SPECT and fluorescence imaging of vulnerable atherosclerotic plaque with a vascular cell adhesion molecule 1 single-chain antibody fragment.
Early detection and evaluation of vulnerable atherosclerotic plaque are important for risk stratification and timely intervention, and vascular cell adhesion molecule 1 (VCAM1) assists in adhesion and recruitment of inflammatory cells to vulnerable lesions. We labeled a single-chain variable fragment (scFv) of VCAM1 with99mtechnetium (99mTc) and fluorescent markers to investigate its potential utility in detecting vulnerable plaques in animal models of atherosclerosis.



We labeled VCAM1 scFv with99mTc and cyanine5 (CY5) and evaluated the probes on apolipoprotein E gene-deficient mice and New Zealand White rabbits with induced atherosclerosis. Histopathology and Western blot examinations confirmed atherosclerotic plaque and VCAM1 expression in the aortas. In vivo biodistribution of99mTc-scFv-VCAM1 was studied. Abdominal organs of mice were removed after CY5-scFv-VCAM1 administration for aortic fluorescence imaging. Rabbits SPECT imaging of99mTc-scFv-VCAM1 was performed and autoradiography (ARG) of the aortas was checked to confirm the tracer uptake.



The radiochemical purity of99mTc-scFv-VCAM1 was 98.72± 1.04% (n = 5) and its specific activity was 7.8 MBq/μg. Biodistribution study indicated predominant probe clearance by kidneys. In fluorescence imaging, stronger signal from CY5-scFv-VCAM1 in the aorta was observed in atherosclerotic mice than that in controls. SPECT imaging with99mTc-scFv-VCAM1 showed tracer uptake in the abdominal aorta and the aortic arch of atherosclerotic animals. ARG confirmed tracer uptake in the aortas of atherosclerotic rabbits, with higher uptake ratios of aortic arch/descending aorta in experimental animals (4.45 ± 0.63, n = 5) than controls (1.12 ± 0.15, n = 5; p < 0.05).



SPECT and fluorescence imaging results showed the feasibility and effectiveness of detecting vulnerable plaque with scFv of VCAM1, indicating its potential for early diagnosis and evaluation of atherosclerosis.
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Chunbao
C
Liu
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xiao
X
Zhang
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Yiling
Y
Song
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Yichun
Y
Wang
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Fengzhen
F
Zhang
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Yingying
Y
Zhang
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: zhyx1229@163.com.
Yongxue
Y
Zhang
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: LXL730724@hotmail.com.
Xiaoli
X
Lan
D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging; D050197:Atherosclerosis / Q000000981:diagnostic imaging; D004797:Enzyme-Linked Immunosorbent Assay; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D008856:Microscopy, Fluorescence; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging*; D011817:Rabbits; D057127:Single-Chain Antibodies / Q000737:chemistry*; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D019010:Vascular Cell Adhesion Molecule-1 / Q000737:chemistry*
D005456:Fluorescent Dyes; D057127:Single-Chain Antibodies; D019010:Vascular Cell Adhesion Molecule-1; D013667:Technetium
Atherosclerosis; Fluorescence imaging; Radionuclide imaging; Single-chain variable fragment antibody; Vascular cell adhesion molecule 1; Vulnerable plaque