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

Abstract

Tumour localisation and tumour to normal tissue ratios of a chimeric anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb), in intact form and as an F(ab')2 fragment labelled with 125I and 131I, were compared in groups of nude mice bearing four different colon cancer xenografts, 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 intact 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 three 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 injection and remained stable or showed only a minor increase thereafter. In contrast, for the F(ab')2 fragment, the tumour to normal tissue ratios increased steadily up to 4 days after injection reaching markedly higher values than those obtained with intact MAb. For the four different 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.

Carcinoembryonic antigen expression, antibody localisation and immunophotodetection of human colon cancer liver metastases in nude mice: A model for radioimmunotherapy

“…It has also been shown that S.C. LS 174T xenografts give a modest antibody uptake (Vogel et al, 1993) and are quite resistant to RIT alone (Buchegger et al, 1995). Thus, this model reflects fairly well the average clinical situation of RIT for colorectal cancer.…”

Preclinical evaluation of a novel CEA‐targeting near‐infrared fluorescent tracer delineating colorectal and pancreatic tumors

“…A variety of approaches have been taken to exploit CEA as a target for cancer imaging. Radiolabeled anti‐CEA antibodies and antibody fragments showed clear tumor visualization of human colon tumors using PET imaging in mouse models . Girgis et al .…”

“…Radiolabeled anti-CEA antibodies and antibody fragments showed clear tumor visualization of human colon tumors using PET imaging in mouse models. 6,12,13 Girgis et al used a relatively large antibody fragment (110 kDa) in a subcutaneous mouse model and clearly demonstrated the potential of CEA-specific antibodies for PET imaging in human pancreatic tumors. 14 Furthermore, phase I trials applying CEAspecific ligands for PET, MRI or a hand-held gamma-detecting probe show early promise.…”

Review: Update on Selection of Optimal Radiopharmaceuticals for Clinical Trials

“…This has been reported for a number of cognate antibodies by our group 10 and others. 11 For tumor targeting, obvious tissues for such comparisons would be derived from murine models involving implanted human cancers in nude mice or spontaneously arising tumors in genetically engineered mice. 12 No mathematical modeling is required in this analysis and the statistical results give a direct answer to the question: Do the agents significantly differ?…”