A. Vaughan

Limitations to the killing of tumours using radiolabelled antibodies

We have calculated the minimum requirements for effective therapy using intravenously administered, tumour-directed antibodies labelled with either iodine 131 or yttrium 90. A lethally large amount of either radionuclide would be required to achieve tumour destruction. At least a 10-fold increase in tumour uptake is necessary to combine tumour destruction with a survivable whole-body dose. The required improvement in specific uptake can be substantially reduced by accelerating the excretion of radioactivity outside the tumour. For all situations studied, yttrium 90 is superior to iodine 131 as a cytotoxic label.

Limiting factors in the localization of tumours with radiolabelled antibodies

The use of radiolabelled antibodies in tumour detection is being intensely studied. Here A. R. Bradwell and colleagues discuss the use of radioimmunolocation and conclude that although many different tumour types can be localized, results at present are no better than with otherscanning techniques. Dramatic improvements will depend upon afuller understanding of tumour cell biology and the optimization of all the parameters that contribute to successful scans.

Characteristics of First and Second Antibodies for Tumour Imaging

Abstract Radiolabelled anti-tumour antibodies (1-Ab) can be cleared from non-tumour areas using a 2nd antibody (2-Ab) to give enhanced tumour:normal tissue ratios and improved tumour detection. Rabbit, mouse and pig IgGs showed higher affinities for human Fc receptors, and were considered potential 2nd antibodies, since immune complexes containing them are rapidly catabolised. In contrast, sheep and chicken antibodies showed no Fc receptor uptake and were considered useful locating antibodies, but of no value as second antibodies. 5 patients were given radiolabelled anti CEA and pig anti sheep IgG 24h later, resulting in a two-fold fall in blood counts, without a large fall in tumour counts. In contrast, patients given mouse IgM and sheep 2-Ab showed no clearance, as predicted by Fc receptor studies.

Limitations in Localizing and Killing Tumors Using Radiolabelled Antibodies

Radiolabelled antibodies against tumours are being studied intensely for their use in tumour detection and tumour destruction. Although a host of different tumour types can be localised, results at present are no better than other scanning techniques. In addition no tumour has been eradicated using labelled antibodies. Dramatic improvements will depend upon a fuller understanding of tumour cell biology and optimising all the parameters involved.

A Model for Cell Killing Using Radiolabelled Antibodies

Abstract A mathematical model has been constructed to determine the dose to solid tumours from tumour seeking antibodies labelled with beta emitting isotopes. Although high tumour uptake of isotope yields high tumour doses, operation of the model has identified the residence time of the isotope within the tumour and normal tissues as a critical factor determining specificity of tumour dose. This finding is open to experimental verification and analysis using the wide range of isotopes which may be bound to chelate labelled antibodies.

Localisation of a Monoclonal Antibody Labelled with Astatine-211 to a Human Heterograft Tumour in Nude Mice

Abstract Antibodies labelled with Astatine-211 are potent cytotoxic agents in an in-vitro system. In an in-vivo tumour model however, the high level of blood radioactivity precludes its direct use as a specific, antitumour agent. A method of simply reducing the level of blood radioactivity is presented.