In vivo distribution of single chain variable fragment (scFv) against atherothrombotic oxidized LDL/β₂-glycoprotein I complexes into atherosclerotic plaques of WHHL rabbits: Implication for clinical PET imaging

详细信息    查看全文

• 作者：Takanori Sasaki^a ; Kazuko Kobayashi^a ; Shoichi Kita^b ; Kazuo Kojima^b ; Hiroyuki Hirano^c ; Lianhua Shen^a ; Fumiaki Takenaka^a ; Hiromi Kumon^a ; ^d ; Eiji Matsuura^a ; ^e ; ^{eijimatu@md.okayama-u.ac.jp}
• 关键词：Autoantibody ; PET/CT imaging ; Oxidized LDL (oxLDL)/β2-glycoprotein I (β2GPI) complexes ; Watanabe heritable hyperlipidemic (WHHL) rabbit
• 刊名：Autoimmunity Reviews
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：16
• 期：2
• 页码：159-167
• 全文大小：995 K
• 卷排序：16

文摘

Oxidized LDL (oxLDL) can exist as a complex with β2-glycoprotein I (β2GPI) in plasma/serum of patients with non-autoimmune atherosclerotic disease or antiphospholipid syndrome (APS). Nonetheless, direct in vivo evidence supporting the pathophysiological involvement of oxLDL/β2GPI complexes and specific autoantibody against the complexes in developing atherothrombosis has yet been established. In the present study, we demonstrated in vivo distribution of single chain variable fragment of IgG anti-oxLDL/β2GPI complexes (3H3-scFv) in Watanabe heritable hyperlipidemic (WHHL) rabbits by PET/CT imaging.MethodsAn antibody-based PET probe, 64Cu-3H3-scFv, was established, and WHHL rabbits were applied for a non-autoimmune atherosclerotic model to demonstrate in vivo distribution of the probe.Results3H3-scFv has exhibits specificity towards β2GPI complexed with oxLDL but neither a free form of β2GPI nor oxLDL alone. Post-intravenous administration of 64Cu-3H3-scFv into WHHL rabbits has demonstrated a non-invasive approach for in vivo visualization of atherosclerotic lesion. The imaging probe achieved ideal blood clearance and distribution for optimal imaging capacity in 24 h, significantly shorter than that of an intact IgG-based imaging probe. 64Cu-3H3-scFv targeted on atherosclerotic plaques in aortas of WHHL rabbits where extensive accumulation of lipid deposits was observed by lipid staining and autoradiography. The accumulation of 64Cu-3H3-scFv in aortic segments of WHHL rabbits was 2.8-folds higher than that of controls (p = 0.0045).ConclusionsThe present in vivo evidence supports the pathophysiological involvement of oxLDL/β2GPI complexes in atherosclerotic complications of WHHL rabbits. 64Cu-3H3-scFv represents a novel PET imaging probe for non-invasive pathophysiological assessment of oxLDL/β2GPI complexes accumulated in atherosclerotic plaques.