title: PET Imaging of Abdominal Aortic Aneurysm with 64Cu-Labeled Anti-CD105 Antibody Fab Fragment.
abstract: The critical challenge in abdominal aortic aneurysm (AAA) research is the accurate diagnosis and assessment of AAA progression. Angiogenesis is a pathologic hallmark of AAA, and CD105 is highly expressed on newly formed vessels. Our goal was to use (64)Cu-labeled anti-CD105 antibody Fab fragment for noninvasive assessment of angiogenesis in the aortic wall in a murine model of AAA.
  
  
  METHODS
  Fab fragment of TRC105, a mAb that specifically binds to CD105, was generated by enzymatic papain digestion and conjugated to NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) for (64)Cu labeling. The binding affinity/specificity of NOTA-TRC105-Fab was evaluated by flow cytometry and various ex vivo studies. BALB/c mice were anesthetized and treated with calcium phosphate to induce AAA and underwent weekly PET scans using (64)Cu-NOTA-TRC105-Fab. Biodistribution and autoradiography studies were also performed to confirm the accuracy of PET results.
  
  
  RESULTS
  NOTA-TRC105-Fab exhibited high purity and specifically bound to CD105 in vitro. Uptake of (64)Cu-NOTA-TRC105-Fab increased from a control level of 3.4 ± 0.1 to 9.5 ± 0.4 percentage injected dose per gram (%ID/g) at 6 h after injection on day 5 and decreased to 7.2 ± 1.4 %ID/g on day 12, which correlated well with biodistribution and autoradiography studies (i.e., much higher tracer uptake in AAA than normal aorta). Of note, enhanced AAA contrast was achieved, due to the minimal background in the abdominal area of mice. Degradation of elastic fibers and highly expressed CD105 were observed in ex vivo studies.
  
  
  CONCLUSIONS
  (64)Cu-NOTA-TRC105-Fab cleared rapidly through the kidneys, which enabled noninvasive PET imaging of the aorta with enhanced contrast and showed increased angiogenesis (CD105 expression) during AAA. (64)Cu-NOTA-TRC105-Fab PET may potentially be used for future diagnosis and prognosis of AAA.
authors.affiliation: Materials Science Program, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Sixiang
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Hakan
authors.initials: H
authors.lastname: Orbay
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Yunan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Graves
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Tapas R
authors.initials: TR
authors.lastname: Nayak
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Reinier
authors.initials: R
authors.lastname: Hernandez
authors.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Haiming
authors.initials: H
authors.lastname: Luo
authors.affiliation: Materials Science Program, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Shreya
authors.initials: S
authors.lastname: Goel
authors.affiliation: TRACON Pharmaceuticals, Inc., San Diego, California; and.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Theuer
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nickles
authors.affiliation: Materials Science Program, University of Wisconsin-Madison, Madison, Wisconsin Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin University of Wisconsin Carbone Cancer Center, Madison, Wisconsin wcai@uwhealth.org.
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001011:Aorta / Q000000981:diagnostic imaging / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging* / Q000276:immunology; D003287:Contrast Media / Q000737:chemistry; D003301:Copper Radioisotopes; D018450:Disease Progression; D004548:Elasticity; D000071063:Endoglin; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry*; D007668:Kidney / Q000000981:diagnostic imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; D003301:Copper Radioisotopes; D000071063:Endoglin; C502004:Eng protein, mouse; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D007140:Immunoglobulin Fab Fragments; D047908:Intracellular Signaling Peptides and Proteins; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; C579557:carotuximab
keywords: CD105 (endoglin); Fab; abdominal aortic aneurysm (AAA); antibody fragment; positron emission tomography (PET)