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

Research output: Contribution to journalArticle

31 Citations (Scopus)

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
Externally publishedYes

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R-1507 monoclonal antibody
Somatomedin Receptors
Single-Photon Emission-Computed Tomography
Sarcoma
Bone and Bones
Heterografts
Therapeutics
Neoplasms
Indium

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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 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

Predicting IGF-1R therapy response in bone sarcomas : Immuno-SPECT imaging with radiolabeled R1507. / Fleuren, Emmy D.G.; Versleijen-Jonkers, Yvonne M.H.; 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.; Van Der Graaf, Winette T.A.

In: Clinical Cancer Research, Vol. 17, No. 24, 15.12.2011, p. 7693-7703.

Research output: Contribution to journalArticle

Fleuren, EDG, Versleijen-Jonkers, YMH, Van De Luijtgaarden, ACM, Molkenboer-Kuenen, JDM, Heskamp, S, Roeffen, MHS, Van Laarhoven, HWM, Houghton, PJ, Oyen, WJG, Boerman, OC & Van Der Graaf, WTA 2011, 'Predicting IGF-1R therapy response in bone sarcomas: Immuno-SPECT imaging with radiolabeled R1507', Clinical Cancer Research, vol. 17, no. 24, pp. 7693-7703. https://doi.org/10.1158/1078-0432.CCR-11-1488
Fleuren EDG, Versleijen-Jonkers YMH, Van De Luijtgaarden ACM, Molkenboer-Kuenen JDM, Heskamp S, Roeffen MHS et al. Predicting IGF-1R therapy response in bone sarcomas: Immuno-SPECT imaging with radiolabeled R1507. Clinical Cancer Research. 2011 Dec 15;17(24):7693-7703. https://doi.org/10.1158/1078-0432.CCR-11-1488
Fleuren, Emmy D.G. ; Versleijen-Jonkers, Yvonne M.H. ; 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. ; Van Der Graaf, Winette T.A. / Predicting IGF-1R therapy response in bone sarcomas : Immuno-SPECT imaging with radiolabeled R1507. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 24. pp. 7693-7703.
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title = "Predicting IGF-1R therapy response in bone sarcomas: Immuno-SPECT imaging with radiolabeled R1507",
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.",
author = "Fleuren, {Emmy D.G.} and Versleijen-Jonkers, {Yvonne M.H.} and {Van De Luijtgaarden}, {Addy C.M.} and Molkenboer-Kuenen, {Janneke D.M.} and Sandra Heskamp and Roeffen, {Melissa H.S.} and {Van Laarhoven}, {Hanneke W.M.} and Houghton, {Peter J} and Oyen, {Wim J.G.} and Boerman, {Otto C.} and {Van Der Graaf}, {Winette T.A.}",
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TY - JOUR

T1 - Predicting IGF-1R therapy response in bone sarcomas

T2 - Immuno-SPECT imaging with radiolabeled R1507

AU - Fleuren, Emmy D.G.

AU - Versleijen-Jonkers, Yvonne M.H.

AU - Van De Luijtgaarden, Addy C.M.

AU - Molkenboer-Kuenen, Janneke D.M.

AU - Heskamp, Sandra

AU - Roeffen, Melissa H.S.

AU - Van Laarhoven, Hanneke W.M.

AU - Houghton, Peter J

AU - Oyen, Wim J.G.

AU - Boerman, Otto C.

AU - Van Der Graaf, Winette T.A.

PY - 2011/12/15

Y1 - 2011/12/15

N2 - 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.

AB - 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.

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