DIRECT COMPARISON OF A RADIOIODINATED INTACT CHIMERIC ANTI-CEA MAB WITH ITS F(AB')(2) FRAGMENT IN NUDE-MICE BEARING DIFFERENT HUMAN COLON-CANCER XENOGRAFTS

Tumour localisation and tumour to normal tissue ratios of a chimeric a nti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb), in intac t form and as an F(ab')2 fragment labelled with I-125 and I-131, were compared in groups of nude mice bearing four different colon cancer xe nografts, T380, Co112 or LoVo, of human origin, or a rat colon cancer transfected with human CEA cDNA, called '3G7'. For each tumour, three to four mice per time point were analysed 6, 12, 24, 48 and 96 h after MAb injection. In the different tumours, maximal localisation of inta ct MAb was obtained at 24 to 48 h, and of F(ab')2 fragment 12 to 24 h after injection. Among the different tumours, localisation was highest with colon cancer T380, with 64% of the injected dose per gram (% ID/ g) for the intact MAb and 57% for its F(ab')2 fragment, while in the t hree other tumours, maximal localisation ranged from 14 to 22% ID g-1 for the intact MAb and was about 11% for the F(ab')2. Tumour to normal tissue ratios of intact MAb increased rapidly until 24 h after inject ion and remained stable or showed only a minor increase thereafter. In contrast, for the F(ab')2 fragment, the tumour to normal tissue ratio s increased steadily up to 4 days after injection reaching markedly hi gher values than those obtained with intact MAb. For the four differen t xenografts, tumour to blood ratios of F(ab')2 were about 2, 3 and 5 to 16 times higher than those of intact antibodies at 12, 24 and 96 h after injection, respectively.