Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507

E. Fleuren, Y. Versleijen-Jonkers, A. van de Luijtgaarden, J. Molkenboer-Kuenen, S. Heskamp, M. Roeffen, H. van Laarhoven, P. Houghton, W. Oyen, O. Boerman and W. van der Graaf

Departments of Medical Oncology and Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Dec, 2011



To investigate whether indium-111-labeled R1507 ((111)In-R1507) immuno-SPECT (single-photon emission computed tomography), a novel noninvasive, in vivo screening method to visualize membranous insulin-like growth factor 1 receptor (IGF-1R) expression and accessibility, can be used to predict IGF-1R treatment (R1507) response in bone sarcomas.BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human bone sarcoma xenografts (OS-1, EW-5, and EW-8) which showed high, modest, or no response, respectively, to R1507, a monoclonal antibody targeting the extracellular domain of IGF-1R. An IGF-1R-negative tumor (OS-33), unresponsive to IGF-1R inhibitors, was examined as well. Mice were injected with (111)In-R1507. Biodistribution and immuno-SPECT/computed tomography imaging studies were carried out 1, 3, and 7 days p.i. in mice with OS-1 and EW-5 xenografts and 3 days p.i. in mice with EW-8 and OS-33 xenografts.Biodistribution studies showed specific accumulation of (111)In-R1507 in OS-1 and EW-5 xenografts (27.5 ± 6.5\%ID/g and 14.0 ± 2.8\%ID/g, 3 days p.i., respectively). Most importantly, (111)In-R1507 uptake in IGF-1R positive, but unresponsive, EW-8 xenografts (6.5 ± 1.5\%ID/g, 3 days p.i.) was similar to that of the IGF-1R-negative OS-33 tumor (5.5 ± 0.6\%ID/g, 3 days p.i.). Uptake in normal tissues was low and nonspecific. Corresponding immuno-SPECT images clearly discriminated between high, modest, and nonresponding tumors by showing a homogeneous (OS-1), heterogeneous (EW-5), or nonspecific (EW-8 and OS-33) tumor uptake of (111)In-R1507.(111)In-R1507 immuno-SPECT is an excellent method to visualize membranous IGF-1R expression and target accessibility in vivo in human bone sarcoma xenografts and may serve as an independent marker to predict IGF-1R therapy (R1507) response in bone sarcoma patients.