The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab')2-R1507 fragments in Ewing sarcomas
SourceEuropean Journal of Cancer, 49, 13, (2013), pp. 2851-2858
Article / Letter to editor
Display more detailsDisplay less details
European Journal of Cancer
SubjectONCOL 2: Age-related aspects of cancer NCEBP 4: Quality of hospital and integrated care; ONCOL 3: Translational research; ONCOL 3: Translational research N4i 1: Pathogenesis and modulation of inflammation; ONCOL 3: Translational research NCMLS 2: Immune Regulation
PURPOSE: To investigate whether F(ab')2-fragments of the monoclonal Insulin-like Growth Factor-1 Receptor (IGF-1R) antibody R1507 (F(ab')2-R1507) can successfully target IGF-1R in Ewing sarcomas (ES). MATERIALS AND METHODS: BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human ES xenografts (EW-5 and EW-8) which previously showed heterogeneous or no uptake of indium-111-labelled R1507 IgG ((111)In-R1507), respectively. Mice were injected with (111)In-F(ab')2-R1507 or (111)In-R1507 as a reference. Biodistribution and immuno-SPECT/computed tomography (CT) imaging studies were carried out 2, 4, 8 and 24h post-injection (p.i.) for (111)In-F(ab')2-R1507 and 24h p.i. for (111)In-R1507. RESULTS: Biodistribution studies showed specific accumulation of (111)In-F(ab')2-R1507 in EW-5 xenografts from t=2h p.i. onwards (3.6+/-0.2%ID/g at t=24h p.i.) and (111)In-F(ab')2-R1507 immuno-SPECT showed almost homogeneous intratumoural distribution at t=24h p.i. Tumour-to-blood ratios of (111)In-F(ab')2-R1507 were significantly higher than those of (111)In-R1507 at t=24h p.i. (2.4+/-0.4 versus 0.5+/-0.1, respectively; p<0.05). More importantly, (111)In-F(ab')2-R1507 also specifically accumulated in EW-8 tumours (3.7+/-0.7%ID/g at t=24h p.i). In both EW-5 and EW-8 tumours, there was a good spatial correlation between IGF-1R expression and (111)In-F(ab')2-R1507 tumour distribution. CONCLUSION: (111)In-F(ab')2-R1507 fragments can successfully target IGF-1R in ES models and have superior tumour penetrating and IGF-1R-targeting properties as compared to (111)In-R1507. This suggests that anti-IGF-1R therapies in ES and other tumours may be improved by using smaller therapeutic compounds, although further in vivo studies addressing this topic are warranted.
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.