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

Emmy D.G. Fleuren, Yvonne M.H. Versleijen-Jonkers, Addy C.M. Van De Luijtgaarden, Janneke D.M. Molkenboer-Kuenen, Sandra Heskamp, Melissa H.S. Roeffen, Hanneke W.M. Van Laarhoven, Peter J. Houghton, Wim J.G. Oyen, Otto C. Boerman, Winette T.A. Van Der Graaf

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Abstract

Purpose: To investigate whether indium-111-labeled R1507 ( 111In-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. Experimental Design: 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 111In-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. Results: Biodistribution studies showed specific accumulation of 111In-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, 111In-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 111In-R1507. Conclusions: 111In-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.

Original languageEnglish (US)
Pages (from-to)7693-7703
Number of pages11
JournalClinical Cancer Research
Volume17
Issue number24
DOIs
StatePublished - Dec 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Fleuren, E. D. G., Versleijen-Jonkers, Y. M. H., Van De Luijtgaarden, A. C. M., Molkenboer-Kuenen, J. D. M., Heskamp, S., Roeffen, M. H. S., Van Laarhoven, H. W. M., Houghton, P. J., Oyen, W. J. G., Boerman, O. C., & Van Der Graaf, W. T. A. (2011). Predicting IGF-1R therapy response in bone sarcomas: Immuno-SPECT imaging with radiolabeled R1507. Clinical Cancer Research, 17(24), 7693-7703. https://doi.org/10.1158/1078-0432.CCR-11-1488