title: Generation and screening of monoclonal antibodies for immunoPET imaging of IGF1R in prostate cancer.
abstract: Insulin-like growth factor 1 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 IGF1R 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 (64)Cu-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 IGF1R was selected and conjugated to NOTA for (64)Cu-labeling. NOTA-1A2G11 maintained IGF1R specificity/avidity based on flow cytometry. (64)Cu-labeling was achieved with good yield (>50%) and high specific activity (>1 Ci/μmol). Serial PET imaging revealed that uptake of (64)Cu-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 IGF1R expression level in the prostate cancer tumor tissues and tumor uptake of (64)Cu-NOTA-1A2G11. Prominent, persistent, and IGF1R-specific uptake of (64)Cu-NOTA-1A2G11 in IGF1R-positive prostate tumors holds strong potential for future cancer diagnosis, prognosis, and therapy using this antibody.
authors.affiliation: Department of Radiology, ‡Materials Science Program, §Department of Medical Physics, and ∥Department of Biochemistry, University of Wisconsin-Madison , Madison, Wisconsin 53705-2275, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Tapas R
authors.initials: TR
authors.lastname: Nayak
authors.forename: Sixiang
authors.initials: S
authors.lastname: Shi
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Graves
authors.forename: Brianne C
authors.initials: BC
authors.lastname: Fliss
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
mesh_terms: D000911:Antibodies, Monoclonal; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D017526:Receptor, IGF Type 1
keywords: antibody; imaging; insulin-like growth factor 1 receptor (IGF1R); positron emission tomography (PET); prostate cancer