Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Jun 18;96(12):1862-70.
doi: 10.1038/sj.bjc.6603806. Epub 2007 May 22.

Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models

E El-Emir  1 , J L J Dearling, A Huhalov, M P Robson, G Boxer, D Neri, G A M S van Dongen, E Trachsel, R H J Begent, R B Pedley
Affiliations

Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models

E El-Emir et al. Br J Cancer. .

Abstract

Angiogenesis is a characteristic feature of tumours and other disorders. The human monoclonal antibody L19- SIP targets the extra domain B of fibronectin, a marker of angiogenesis expressed in a range of tumours. The aim of this study was to investigate whole body distribution, tumour localisation and the potential of radioimmunotherapy with the L19-small immunoprotein (SIP) in colorectal tumours. Two colorectal tumour models with highly different morphologies, the SW1222 and LS174T xenografts, were used in this study. Localisation and retention of the L19-SIP antibody at tumour vessels was demonstrated using immunohistochemistry and Cy3-labelled L19-SIP. Whole body biodistribution studies in both tumour models were carried out with (125)I-labelled L19-SIP. Finally, (131)I-labelled antibody was used to investigate the potential of radioimmunotherapy in SW1222 tumours. Using immunohistochemistry, we confirmed extra domain B expression in the tumour vasculature. Immunofluorescence demonstrated localisation and retention of injected Cy3-labelled L19-SIP at the abluminal side of tumour vessels. Biodistribution studies using a (125)I-labelled antibody showed selective tumour uptake in both models. Higher recorded values for localisation were found in the SW1222 tumours than in the LS174T (7.9 vs 6.6 %ID g(-1)), with comparable blood clearance for both models. Based on these results, a radioimmunotherapy study was performed in the SW1222 xenograft using (131)I-Labelled L19-SIP (55.5 MBq), which showed selective tumour uptake, tumour growth inhibition and improved survival. Radio- and fluorescence-labelled L19-SIP showed selective localisation and retention at vessels of two colorectal xenografts. Furthermore, (131)I-L19-SIP shows potential as a novel treatment of colorectal tumours, and provides the foundation to investigate combined therapies in the same tumour models.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Immunohistochemical and immunofluorescence staining with L19-SIP antibody in SW1222 and LS174T xenograft-bearing mice. (A) Immunohistochemical staining of SW1222 xenograft lines with L19-SIP antibody. (B–D) Multiple digital fluorescence images of an LS174T tumour injected with Cy3-labelled L19-SIP antibody for 6 h demonstrating (B) perfusion, (C) blood vessel staining and (D) L19-SIP in the same tumour section. (E) Triple fluorescence staining of CD31 (green), L19-SIP (red) and DAPI (blue) in LS174T tumours. (F) High-power image of CD31 (green), L19-SIP (red) and Hoechst (blue) staining in LS174T (arrow indicating abluminal localisation of the L19-SIP antibody). All images are at × 20 magnification except (F) which is at × 40 magnification.
Figure 2
Figure 2
Biodistribution of intravenously injected 125I-L19-SIP in SW1222 xenograft-bearing mice at 1, 3, 6 and 24 h after injection. The mean±s.d. of four different mice are shown.
Figure 3
Figure 3
Biodistribution of intravenously injected 125I-L19-SIP in LS174T xenograft-bearing mice at 1, 3, 6 and 24 h after injection. The mean±s.d. of four different mice are shown.
Figure 4
Figure 4
Blood stability data. Antigen binding of 125I-L19-SIP in blood of LS174T tumour-bearing mice at 1, 3, 6 and 24 h post-injection. The mean±s.d. of four different mice are shown. Binding of the labelled protein before injection was 84.11%.
Figure 5
Figure 5
Biodistribution of intravenously injected 131I-L19-SIP in SW1222 xenograft-bearing mice at 3, 24 and 72 h after injection. The mean±s.d. of four different mice are shown.
Figure 6
Figure 6
Tumour volumes of control and treated SW1222 xenografts following a single injection of 55.5 MBq of 131I-L19-SIP. The mean±s.e.m. of six mice for the control and four mice for the treated groups are shown.
Figure 7
Figure 7
Survival of SW1222 xenograft-bearing nude mice after a single injection of 55.5 MBq of 131I-L19-SIP.
Figure 8
Figure 8
Individual body weights of (A) control and (B) treated mice bearing SW1222 xenografts, after a single injection of 55.5 MBq of 131I-L19-SIP.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alessi P, Ebbinghaus C, Neri D (2004) Molecular targeting of angiogenesis. Biochim Biophys Acta 1654(1): 39–49 - PubMed
    1. Berndorff D, Borkowski S, Sieger S, Rother A, Friebe M, Viti F, Hilger CS, Cyr JE, Dinkelborg LM (2005) Radioimmunotherapy of solid tumours by targeting extra domain B fibronectin: identification of the best-suited radioimmunoconjugate. Clin Cancer Res 11(19 Part 2): 7053s–7063s - PubMed
    1. Birchler M, Viti F, Zardi L, Spiess B, Neri D (1999) Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment. Nat Biotechnol 17(10): 984–988 - PubMed
    1. Birchler MT, Milisavlijevic D, Pfaltz M, Neri D, Odermatt B, Schmid S, Stoeckli SJ (2003) Expression of the extra domain B of fibronectin, a marker of angiogenesis, in head and neck tumours. Laryngoscope 113(7): 123 - PubMed
    1. Borsi L, Balza E, Bestagno M, Castellani P, Carnemolla B, Biro A, Leprini A, Sepulveda J, Burrone O, Neri D, Zardi L (2002) Selective targeting of tumoural vasculature: comparison of different formats of an antibody (L19) to the ED-B domain of fibronectin. Int J Cancer 102(1): 75–85 - PubMed