Immunoreactivity, pharmacokinetics and bone marrow dosimetry of intrathecal radioimmunoconjugates

Abstract

Ten patients with neoplastic meningitis were treated with a variety of ¹³¹1‐monoclonal antibody (MAb) conjugates, chosen to bind to their particular malignancy. Pharmacokinetic studies revealed that MAbs leave the ventricular compartment, enter the sub‐arachnoid space and then pass into the blood. Once the MAbs enter the blood compartment, their clearance is determined by factors such as circulating anti‐mouse Ig and circulating antigens. These lead to complex formations and the clearance of the conjugate by the ireticuloendothelial system. In one individual, the anti‐mouse Ig response observed systemically was not mirrored within the CSF, which has implications for planning future therapy of this type. In other patients, formation of immune complexes was due to binding to circulating antigen within the blood. The major toxicity associated with the intrathecal administration of ¹³¹1‐MAbs was bone‐marrow suppression. The doses to the bone marrow, resulting from the form of therapy, were calculated but showed no direct correlation with WHO grade 3/4 toxicity. Doses to the ventricular lining werct also calculated, but due to the complex geometry of the compartment, calculation of potential tumour doses was not practicable.