Journal article
PET Imaging of Abdominal Aortic Aneurysm with Cu-64-Labeled Anti-CD105 Antibody Fab Fragment
The Journal of nuclear medicine (1978), Vol.56(6), pp.927-932
06/01/2015
DOI: 10.2967/jnumed.114.153098
PMCID: PMC4452422
PMID: 25883125
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 Cu-64-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 Cu-64 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 Cu-64-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 Cu-64-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. Conclusion: Cu-64-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. Cu-64-NOTA-TRC105-Fab PET may potentially be used for future diagnosis and prognosis of AAA.
Details
- Title: Subtitle
- PET Imaging of Abdominal Aortic Aneurysm with Cu-64-Labeled Anti-CD105 Antibody Fab Fragment
- Creators
- Sixiang Shi - University of Wisconsin–MadisonHakan Orbay - University of Wisconsin–MadisonYunan Yang - University of Wisconsin–MadisonStephen A. Graves - University of Wisconsin–MadisonTapas R. Nayak - University of Wisconsin–MadisonHao Hong - University of Wisconsin–MadisonReinier Hernandez - University of Wisconsin–MadisonHaiming Luo - University of Wisconsin–MadisonShreya Goel - Univ Wisconsin, Mat Sci Program, Madison, WI 53705 USACharles P. Theuer - Tracon PharmaceuticalsRobert J. Nickles - University of Wisconsin–MadisonWeibo Cai - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- The Journal of nuclear medicine (1978), Vol.56(6), pp.927-932
- Publisher
- Soc Nuclear Medicine Inc
- DOI
- 10.2967/jnumed.114.153098
- PMID
- 25883125
- PMCID
- PMC4452422
- ISSN
- 0161-5505
- eISSN
- 1535-5667
- Number of pages
- 6
- Grant note
- T32GM008349 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) DGE-1256259 / National Science Foundation; National Science Foundation (NSF) University of Wisconsin-Madison W81XWH-11-1-0644; W81XWH-11-1-0648 / Department of Defense; United States Department of Defense NIBIB/NCI 1R01CA169365; P30CA014520; 5T32GM08349; T32CA009206 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA T32CA009206 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 125246-RSG-13-099-01-CCE / American Cancer Society
- Language
- English
- Date published
- 06/01/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383279002771
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