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ImmunoSPECT and ImmunoPET of IGF-1R Expression with the Radiolabeled Antibody R1507 in a Triple-Negative Breast Cancer Model

2010; Society of Nuclear Medicine and Molecular Imaging; Volume: 51; Issue: 10 Linguagem: Inglês

10.2967/jnumed.110.075648

1535-5667

Sandra Heskamp, Hanneke W.M. van Laarhoven, Janneke D.M. Molkenboer‐Kuenen, Gerben M. Franssen, Yvonne M.H. Versleijen‐Jonkers, Wim J.G. Oyen, Winette T.A. van der Graaf, Otto C. Boerman,

Cancer, Hypoxia, and Metabolism

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.