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

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.

Evaluation of diagnosis-related groups in the National Health Service.

Evaluation of the use of diagnosis-related groups (DRGs) has revealed a number of technical problems in coding of diagnoses and operative procedures, as well as unresolved issues in the clinical acceptability of existing groupings. An investigation of the statistical homogeneity of DRGs, in terms of duration of patient stay, is described. Consideration of data relating to some 990,000 episodes of in-patient care in three English Regions discloses wide variations in statistical homogeneity, both between DRGs and in relation to individual clinical specialties. The greatest homogeneity is found in ENT surgery and gynaecology; and the least in general medicine and orthopaedic surgery. The need for improved data collection and coding procedures is discussed, together with the advisability of sensitivity in the interpretation of DRGs, as well as the need for a co-ordinated approach to their refinement for application in any wider introduction in the NHS.