title: Positron emission tomography imaging of CD105 expression in a rat myocardial infarction model with (64)Cu-NOTA-TRC105.
abstract: Biological changes following myocardial infarction (MI) lead to increased secretion of angiogenic factors that subsequently stimulate the formation of new blood vessels as a compensatory mechanism to reverse ischemia. The goal of this study was to assess the role of CD105 expression during MI-induced angiogenesis by positron emission tomography (PET) imaging using (64)Cu-labeled TRC105, an anti-CD105 monoclonal antibody. MI was induced by ligation of the left anterior descending (LAD) artery in female rats. Echocardiography and (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET scans were performed on post-operative day 3 to confirm the presence of MI in the infarct group and intact heart in the sham group, respectively. Ischemia-induced angiogenesis was non-invasively monitored with (64)Cu-NOTA-TRC105 (an extensively validated PET tracer in our previous studies) PET on post-operative days 3, 10, and 17. Tracer uptake in the infarct zone was highest on day 3 following MI, which was significantly higher than that in the sham group (1.41 ± 0.45 %ID/g vs 0.57 ± 0.07 %ID/g; n=3, p<0.05). Subsequently, tracer uptake in the infarct zone decreased over time to the background level on day 17, whereas tracer uptake in the heart of sham rats remained low at all time points examined. Histopathology documented increased CD105 expression following MI, which corroborated in vivo findings. This study indicated that PET imaging of CD105 can be a useful tool for MI-related research, which can potentially improve MI patient management in the future upon clinical translation of the optimized PET tracers.
authors.affiliation: Department of Radiology, University of Wisconsin - Madison WI, USA.
authors.forename: Hakan
authors.initials: H
authors.lastname: Orbay
authors.affiliation: Department of Medical Physics, University of Wisconsin - Madison WI, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Physics, University of Wisconsin - Madison WI, USA.
authors.forename: Hector F
authors.initials: HF
authors.lastname: Valdovinos
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, University of Wisconsin - Madison WI, USA.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Medical Physics, University of Wisconsin - Madison WI, USA.
authors.forename: Reinier
authors.initials: R
authors.lastname: Hernandez
authors.affiliation: TRACON Pharmaceuticals, Inc. San Diego, CA, USA.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Theuer
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, University of Wisconsin - Madison WI, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Hacker
authors.affiliation: Department of Medical Physics, University of Wisconsin - Madison WI, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nickles
authors.affiliation: Department of Radiology, University of Wisconsin - Madison WI, USA ; Department of Medical Physics, University of Wisconsin - Madison WI, USA ; University of Wisconsin Carbone Cancer Center Madison, WI, USA.
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
keywords: 64Cu; Angiogenesis; CD105 (endoglin); molecular imaging; myocardial infarction (MI); positron emission tomography (PET)