Abstract 5283: MicroSPECT imaging of IGF1R expression with radiolabeled R1507 in osteosarcoma models
Authors: Fleuren Emmy DG , Versleijen-Jonkers Yvonne MH , van de Luijtgaarden Addy CM , Molkenboer-Kuenen Janneke DM , Roeffen Melissa HS , van Laarhoven Hanneke WM , Boerman Otto C. , Oyen Wim JG , van der Graaf Winette TA 
Published: June 2012

Introduction: Osteosarcoma is an aggressive form of bone cancer affecting mainly children and young adults. Despite intensive chemotherapeutic schedules, many patients still die from the disease. Therefore, new treatment strategies are being explored, such as anti-IGF1R antibody treatment. Early results from phase II studies using IGF1R antibodies demonstrated clinically relevant activity in osteosarcomas, and there is a clear need for optimal patient selection for this new treatment. First of all, membranous tumor IGF1R expression is required to benefit from this therapy. However, accurate IGF1R expression levels remain difficult to determine, since target expression can change over time and patients may present with multiple tumor manifestations demonstrating variable target expression. Obviously, it is not feasible to perform multiple biopsies. Therefore, the aim of the present study is to develop a noninvasive in vivo imaging method using radiolabeled antibodies, to visualize IGF1R expression in osteosarcomas.

Methods: R1507, a monoclonal antibody directed against an extracellular epitope of the IGF1R, was radiolabeled with 111Indium (111In) and used to determine IGF1R expression in vivo in BALB/c nude mice bearing either IGF1R-positive or IGF1R-negative subcutaneous human osteosarcoma xenografts (OS1 and OS33, respectively). Mice were i.v. injected with 3 μg R1507 as optimal tumor targeting dose, or with an excess of unlabeled R1507 (300 μg) to determine the nonspecific accretion of the antibody in the tumor. Biodistribution and microSPECT imaging studies were performed 1, 3 and 7 days p.i. in mice with OS1 xenografts and at day 3 p.i. in mice with OS33 xenografts.

Results: Biodistribution studies showed specific accumulation of 111In-R1507 in the OS1 xenografts from day 1 p.i. onwards (15.7 ± 4.0 %ID/g), and uptake levels increased even further on day 3 and 7 (27.5 ± 6.5 %ID/g and 25.8 ± 5.8 %ID/g, resp.). Uptake in other organs was low, and best tumor-to-blood ratios were seen at day 7 p.i. (4.5 ± 1.4). The accumulation was clearly visualized with microSPECT from day 1 p.i. onwards.

In contrast, 111In-R1507 uptake in the IGF1R-negative OS33 xenografts did not exceed background levels (5.5 ± 0.6 %ID/g; tumor-to-blood: 1.2 ± 0.4), and differed significantly from the uptake in the OS1 tumors at all time points (p&lt;0.05). On microSPECT scans, IGF1R-positive tumors could therefore clearly be distinguished from IGF1R-negative tumors.

Conclusion: 111In-R1507 microSPECT imaging is an excellent method to visualize membranous IGF1R expression in vivo in human osteosarcoma xenografts. In addition, IGF1R-negative xenografts remained negative on microSPECT scans. These findings confirm that this novel technique can potentially be used to noninvasively determine IGF1R expression in osteosarcoma patients, which may allow better selection of patients who could benefit from IGF1R targeted therapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5283. doi:10.1158/1538-7445.AM2011-5283