1. ¹Cancer Research UK Targeting and Imaging Group, Department of Oncology, Royal Free and University College Medical School (UCL), Hampstead Campus, Rowland Hill Street, London NW3 2PF, UK
2. ²Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Wolfgang-Pauli-Str. 10, ETH Hoenggerberg, HCI G396, Zurich CH-8093, Switzerland
3. ³Department of Otolaryngology/Head and Neck Surgery, VU University Medical Centre, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands

Correspondence: Dr E El-Emir, E-mail: e.el-emir@ucl.ac.uk

Revised 19 April 2007; Accepted 24 April 2007; Published online 22 May 2007.

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 ¹²⁵I-labelled L19-SIP. Finally, ¹³¹I-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 ¹²⁵I-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 ¹³¹I-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, ¹³¹I-L19-SIP shows potential as a novel treatment of colorectal tumours, and provides the foundation to investigate combined therapies in the same tumour models.