Treatment of Diffuse Leptomeningeal Malignancy by Intrathecal Injection of ¹³¹I Radioimmunoconjugates

Abstract

It is clear from a variety of different studies that monoclonal antibodies (MAbs), as either biological response modifiers or targeting agents, cannot be used successfully for the treatment of large tumour deposits. With whole immunoglobulin (Ig), insufficient MAb enters bulk disease to elicit a major cytotoxic effect. This is in marked contrast to the results obtained in the human xenograft/nude mouse models where relatively large tumours can be eliminated with systemically administered MAbs carrying drugs (Embelton and Garnett 1985), toxins (Thorpe et al. 1985), or radionuclides (Jones et al. 1985). Differences between the mouse model and the clinical studies include the dilution of the MAb conjugate in a relatively large circulating blood volume in patients, increased interstitial pressure in tumours as compared to normal organs (Jain 1988) and poor penetration of antibody from the systemic compartment to the interstitial space (Herlyn and Koprowski 1982). Whilst the use of antibody fragments improves their tumour penetration, this is at the expense of a faster blood clearance (Sutherland et al. 1987). The overall benefit in targeting seen with the use of antibody fragments is therefore relatively small.