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Eur J Cancer. 2013 Sep;49(13):2851-8. doi: 10.1016/j.ejca.2013.04.009. Epub 2013 May 8.

The strength of small: improved targeting of insulin-like growth factor-1 receptor (IGF-1R) with F(ab')₂-R1507 fragments in Ewing sarcomas.

Author information

1
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. E.Fleuren@onco.umcn.nl

Abstract

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 24 h post-injection (p.i.) for (111)In-F(ab')₂-R1507 and 24 h 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=2 h p.i. onwards (3.6 ± 0.2%ID/g at t = 24 h 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=24 h 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 = 24 h 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.

KEYWORDS:

Ewing sarcoma; F(ab′)(2); IGF-1R; Immuno-SPECT; R1507

PMID:
23664098
DOI:
10.1016/j.ejca.2013.04.009
[Indexed for MEDLINE]

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