ImmunoSPECT and immunoPET of IGF-1R expression with the radiolabeled antibody R1507 in a triple-negative breast cancer model

S. Heskamp, H. van Laarhoven, J. Molkenboer-Kuenen, G. Franssen, Y. Versleijen-Jonkers, W. Oyen, W. van der Graaf and O. Boerman

Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Oct, 2010



The insulinlike growth factor 1 receptor (IGF-1R) is a new target for the treatment of breast cancer. Patients with breast cancer lesions that express IGF-1R may benefit from treatment with anti-IGF-1R antibodies. Therefore, the aim of the present study was to develop a noninvasive, in vivo imaging method, using radiolabeled antibodies, to visualize IGF-1R expression.R1507 is a monoclonal antibody directed against the IGF-1R. In vitro, the affinity and internalization kinetics of (111)In-R1507 were determined using the IGF-1R-expressing triple-negative breast cancer cell line SUM149. In vivo, the pharmacodynamics of (111)In-R1507 and (125)I-R1507 were determined in mice with subcutaneous SUM149 tumors. (111)In-R1507 SPECT and (89)Zr-R1507 PET images of mice with subcutaneous SUM149 tumors were acquired at 1, 3, and 7 d after injection.(111)In-R1507 (concentration required to inhibit binding by 50\%, 0.1 nM) was slowly internalized by SUM149 cells. (111)In-R1507 specifically and efficiently accumulated in the SUM149 xenografts: the tumor uptake was 20 percentage injected dose per gram (\%ID/g), 33 \%ID/g, and 31 \%ID/g at 1, 3, and 7 d after injection, respectively. (125)I-R1507 accumulated in the tumor less efficiently. Small-animal SPECT and small-animal PET of mice clearly visualized the subcutaneous SUM149 xenograft, with increasing contrast at later time points.(111)In-R1507 and (89)Zr-R1507 are new tracers to noninvasively determine IGF-1R expression in vivo in breast cancer xenografts using SPECT and PET. In the future, these techniques may enable patient selection for IGF-1R-targeted therapy.