The
insulin-like growth factor 1 receptor (IGF-1R) is a potential 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. IGF-1R expression can be visualized using radiolabeled
R1507, a
monoclonal antibody directed against IGF-1R. However,
antibodies clear slowly from the circulation, resulting in low
tumor-to-background ratios early after injection. Therefore, we aimed to accelerate targeting of IGF-1R using radiolabeled
R1507 F(ab')2 and
Fab fragments. In vitro, immunoreactivity, binding affinity and internalization of
R1507 IgG, F(ab')2 and Fab were determined using the triple negative IGF-1R-expressing
breast cancer cell line SUM149. In vivo, pharmacokinetics of (111)In-labeled
R1507 IgG, F(ab')2 and Fab were studied in mice bearing subcutaneous SUM149 xenografts. SPECT/CT images were acquired and the biodistribution was measured ex vivo. The in vitro binding characteristics of radiolabeled
R1507 IgG and F(ab')2 were comparable, whereas the affinity of
Fab fragments was significantly lower (Kd: 0.6 nM, 0.7 nM and 3.0 nM for
R1507 IgG, F(ab')2 and Fab, respectively). Biodistribution studies showed that the maximum
tumor uptake of (111)In-R1507
IgG, F(ab')2 and Fab was 31.8% ID/g (72 h p.i.), 10.0% ID/g (6 h p.i.), and 1.8% ID/g (1 h p.i.), respectively. However, maximal
tumor-to-blood ratios for F(ab')2 (24 h p.i.: 7.5) were more than twice as high as those obtained with
R1507 (72 h p.i.: 2.8) and Fab (6 h p.i.: 2.8). Injection of an excess of unlabeled
R1507 significantly reduced
tumor uptake, suggesting that the uptake of
R1507 IgG and F(ab')2 was specific for IGF-1R, while the major fraction of the
tumor uptake of Fab was nonspecific. IGF-1R-expressing xenografts were visualized with (111)In-F(ab')2 SPECT/CT as early
as 6 h p.i., while with
R1507 IgG, the
tumor could be visualized after 24 h. No specific targeting was observed with (111)In-Fab. (111)In-F(ab')2 fragments showed improved targeting of IGF-1R expressing
tumors.
Tumor-to-blood ratios were twice as high as those obtained with (111)In-R1507, and adequate
tumor targeting on SPECT/CT images was observed as early
as 6 h p.i. For individualization and optimization of IGF-1R targeted
therapy, (111)In-F(ab')2 may be the tracer of choice.