Predicting IGF-1R Therapy Response in Bone Sarcomas: Immuno-SPECT Imaging with Radiolabeled R1507

• Published in: Clinical cancer research Vol. 17; no. 24; pp. 7693 - 7703
• Main Authors: FLEUREN, Emmy D. G, VERSLEIJEN-JONKERS, Yvonne M. H, VAN DER GRAAF, Winette T. A, VAN DE LUIJTGAARDEN, Addy C. M, MOLKENBOER-KUENEN, Janneke D. M, HESKAMP, Sandra, ROEFFEN, Melissa H. S, VAN LAARHOVEN, Hanneke W. M, HOUGHTON, Peter J, OYEN, Wim J. G, BOERMAN, Otto C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.12.2011
• Subjects: Animals; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - pharmacology; Antineoplastic agents; Biological and medical sciences; Bone Neoplasms - diagnostic imaging; Bone Neoplasms - drug therapy; Bone Neoplasms - pathology; Cell Line, Tumor; Diseases of the osteoarticular system; Female; Humans; Immunohistochemistry; Indium Radioisotopes; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Pharmacology. Drug treatments; Positron-Emission Tomography - methods; Prognosis; Receptor, IGF Type 1 - antagonists & inhibitors; Receptor, IGF Type 1 - metabolism; Reproducibility of Results; Sarcoma - diagnostic imaging; Sarcoma - drug therapy; Sarcoma - pathology; Tissue Distribution; Tomography, Emission-Computed, Single-Photon - methods; Tumors of striated muscle and skeleton; Xenograft Model Antitumor Assays; Radionuclide study; Radiolabelling; Sarcoma; Diseases of the osteoarticular system; Prediction; Malignant tumor; Single photon emission tomography; Photon; type I insulin-like growth factor receptor; Osteoarticular system; Treatment; Osteosarcoma; Imaging; Medical imagery; Bone; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-11-1488

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.