Abstract A36: ImmunoSPECT and ImmunoPET imaging of IGF-1R expression in a model for triple negative breast cancer

Abstract

Abstract Introduction: Triple negative breast cancer has a poor prognosis and chemotherapy is currently the mainstay of treatment. A potential new target for the treatment of triple negative breast cancer is the insulin-like growth factor 1 receptor (IGF-1R). Patients with triple negative breast cancer lesions that express the IGF-1R (30 to 40%) may be most suited to be treated with IGF-1R antibodies. Therefore, the aim of the present study was to develop a noninvasive, in vivo imaging method, using radiolabeled R1507, to visualize IGF-1R expression. Material and methods: R1507, a monoclonal antibody directed against an epitope on the extracellular domain of the IGF-1R, was radiolabeled with 111Indium (111In), 125Iodine (125I) and 89Zirconium (89Zr). In vitro, the affinity and internalization kinetics of 111In-R1507 were determined using the IGF-1R expressing breast cancer cell line SUM149 (ER, PR and HER2 negative). In vivo studies were performed in BALB/c nude mice with subcutaneous SUM149 xenografts. To determine the pharmacodynamics of R1507, mice received an intravenous injection of 111In-R1507 and 125I-R1507. One, three and seven days post injection, mice were killed and ex vivo tumor uptake was measured. Non-specific uptake was determined by coinjection of an excess unlabeled R1507. A dose escalation study was performed with 111In-R1507 to determine the optimal protein dose of R1507 for in vivo imaging (dose range 1 – 1000 μg). Finally, SPECT and PET images were acquired of mice with subcutaneous SUM149 tumors one, three and seven days post injection of 111In-R1507 and 89Zr-R1507, respectively. Results: 111In-R1507 (IC50 = 0.1 nM) was slowly internalized by SUM149 cells. 111In-R1507 specifically and efficiently accumulated in the SUM149 xenografts: the specific tumor uptake was 20% ID/g, 33% ID/g and 31% ID/g at one, three and seven days post injection, respectively. The dose escalation study showed that the optimal dose for imaging experiments was ≤ 3 μg (tumor uptake: 35% ID/g). MicroSPECT and microPET imaging of mice clearly visualized the subcutaneous SUM149 xenograft with increasing contrast at later time points. Conclusion: 111In-R1507 SPECT and 89Zr-R1507 PET are excellent methods to visualize IGF-1R expression in vivo in triple negative breast cancer xenografts. In the future, these techniques may enable selection of patients with triple negative breast cancer for IGF-1R targeted therapy. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A36