In vivo studies on the uptake of radiolabelled antibodies by colorectal and gastric carcinoma xenografts

Abstract

A number of criteria have been investigated to try to improve the uptake of radiolabelled antibodies by colorectal carcinoma xenografts. The in vivo behaviour of four antibodies was compared and found to vary. Two antibodies, 11-285-14 and 14-95-55, demonstrated specific uptake by the tumours. 11-357-5 was lost from the tumour after 72 h and the fourth antibody could not be iodinated without loss of activity. Neither increased time nor increased dose were shown to increase the uptake of antibody by tumours although the clearance of antibody from blood was shown to be more rapid than from tumour resulting in clearer backgrounds. Increased tumour:blood ratios were demonstrated by particular combinations of antibodies but the extent to which this occurred varied with the epitopes recognised. High carcinoembryonic antigen expressing xenografts did not show significantly higher uptake of antibody. This was shown to be due to the smaller size of these tumours and associated decreased vascularity.

Biodistribution and histological localization of anti‐human colon cancer monoclonal antibody (MAb) 1A3: The influence of administered MAB dose on tumor uptake

“…Scale bar = 480pm (a,c,e), 120pm (b,d,f). Duewell et al, 1986;Macdonald et al, 1986;Wahl et al, 1986;Sharkey et al, 1987), or by a failure to see a plateau in the Fg of antibody bound to tumor (Beaumier et al, 1985). Tumor sizes varied in these studies, as did the model system and the tumor specificity of the MAb.…”

“…The extent to which tumor's antigen binding sites can become saturated with MAbs should determine the dose range across which injected MAbs are most useful for radioimmunoimaging and therapy (Carter, 1985). Several studies have addressed the question of in vivo tumor binding of MAbs as a function of increasing dose (Murray et al, 1985;Duewell et al, 1986;Macdonald et al, 1986;Rogers et al, 1986b;Wahl et al, 1986;Sharkey et al, 1987;Patt et al, 1988) but relatively few (Pimm and Baldwin, 1984;Badger et al, 1985;Beaumier et al, 1985;Schroff et al, 1987;Matzku et al, 1989) were able to demonstrate saturation kinetics of tumor or non-tumor tissue. The relatively large size of tumors most often used as targets (> 1 .Og) coupled with the relatively low dose ranges of MAb frequently examined (<loo@ may explain these results.…”