Safe, effective high activity radiolabelling of monoclonal antibodies for radioimmunotherapy: 131I-anti-CD 20 monoclonal antibody therapy of non-Hodgkins lymphoma

Full text: Immunotherapy of relapsed or refractory non-Hodgkins lymphoma (NHL) with anti-CD20 antibodies has an overall response rate (ORR) of 40%, mean duration six months, whereas radioimmunotherapy using radiolabelled antibody has an ORR of >80%, duration twelve months. These radioimmunopharmaceuticals are not available in Australia. Mabthera (rituximab), an anti-CD20 antibody approved for use in Australia for treatment of NHL, has been successfully radiolabelled in the radiochemistry laboratory at Fremantle Hospital for pilot clinical studies of RIT. Activities of up to 5 GBq 131I-Mabthera have been prepared in a custom-designed semi-automated shielded system which includes sterile, pyrogen-free disposable fittings designed to be available as a commercial kit, installed inside a fume cupboard. The Chloramine-T reaction was carried out under remote control in the 131I purpose-designated 10ml shipping vial to minimise operator exposure. Typically 80% of initial 131I activity was recovered as labelled product (purity > 96.5%). Primary reagents were tested for sterility and pyrogens, and the 131I-Mabthera was assayed for immunoreactivity. Prospective dosimetry was performed on each patient using whole body retention data obtained over a period of seven days following tracer administration of 200 MBq. Safe administration of therapy activities up to 2.9 GBq at the patient's bedside in the radiopharmaceutical treatment suite was achieved using a novel intravenous infusion pump system which was shielded with custom-designed apparatus. Objective response was documented in eight out of nine evaluable patients. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc