Journal article
Generation and Screening of Monoclonal Antibodies for ImmunoPET Imaging of IGF1R in Prostate Cancer
Molecular pharmaceutics, Vol.11(10), pp.3624-3630
10/06/2014
DOI: 10.1021/mp5003637
PMCID: PMC4186682
PMID: 25157758
Abstract
Insulin-like growth factor I receptor (IGF1R) plays an important role in proliferation, apoptosis, angiogenesis, and tumor invasion. The expression level of IGF1R is related to resistance to several targeted therapies. The goal of this study was to develop an immunoPET tracer for imaging of IGF1R in prostate cancer. Murine antibodies against human IGFIR were generated in BALB/c mice, which were screened in IGF1R-positive MCF-7 cells using flow cytometry as well as biodistribution studies with multiple Cu-64-labeled antibody clones. The antibody production method we adopted could readily produce milligram quantities of anti-IGF1R antibodies for in vivo studies. One antibody clone (1A2G11) with the highest affinity for IGFIR was selected and conjugated to NOTA for Cu-64-labeling. NOTA-1A2G11 maintained IGFIR specificity/avidity based on flow cytometry. Cu-64-labeling was achieved with good yield (>50%) and high specific activity (>1 Ci/mu mol). Serial PET imaging revealed that uptake of Cu-64-NOTA-1A2G11 was 2.8 +/- 0.7, 10.2 +/- 2.6, and 9.6 +/- 1.7 %ID/g in IGF1R-positive DU-145 tumors at 4, 24, and 48 h postinjection, respectively (n = 3), significantly higher than that in IGF1R-negative LNCaP tumors (<3 %ID/g at each time point) except at 4 h postinjection. Histology studies showed strong correlations between IGFIR expression level in the prostate cancer tumor tissues and tumor uptake of Cu-64-NOTA-1A2G11. Prominent, persistent, and IGFIR-specific uptake of Cu-64-NOTA-1A2G11 in IGF1R-positive prostate tumors holds strong potential for future cancer diagnosis, prognosis, and therapy using this antibody.
Details
- Title: Subtitle
- Generation and Screening of Monoclonal Antibodies for ImmunoPET Imaging of IGF1R in Prostate Cancer
- Creators
- Hao Hong - University of Wisconsin–MadisonTapas R. Nayak - University of Wisconsin–MadisonSixiang Shi - University of Wisconsin–MadisonStephen A. Graves - University of Wisconsin–MadisonBrianne C. Fliss - University of Wisconsin–MadisonTodd E. Barnhart - University of Wisconsin–MadisonWeibo Cai - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Molecular pharmaceutics, Vol.11(10), pp.3624-3630
- DOI
- 10.1021/mp5003637
- PMID
- 25157758
- PMCID
- PMC4186682
- NLM abbreviation
- Mol Pharm
- ISSN
- 1543-8384
- eISSN
- 1543-8392
- Publisher
- Amer Chemical Soc
- Number of pages
- 7
- Grant note
- 125246-RSG-13-099-01-CCE / American Cancer Society University of Wisconsin-Madison W81XWH-11-1-0644 / Department of Defense; United States Department of Defense R01CA169365 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NIBIB/NCI 1R01CA169365; P30CA014520 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 10/06/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383281102771
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