A pilot study was performed to investigate the toxicity and therapeutic effect of radiolabeled antibody administered intrathecally in patients with leptomeningeal tumors. Five patients who failed conventional therapy received between 11 mCi and 40 mCi of radiolabeled antibody. The choice of antibody varied depending on the immunophenotype of the tumor. Therapy was well tolerated generally, with minimal acute toxicity. Four of five patients achieved an objective response to treatment that has been sustained for a period varying from 7 months to 2 years. No clinical signs of chronic toxicity have been observed in patients 1 and 2 years after therapy.
Monoclonal antibody UJ13A, radiolabelled with 131I, was intravenously administered to patients with primary brain tumours. The antigen recognised by UJ13A is present on most neuroectodermally derived tissue. The ratio of uptake in tumour to normal brain, assessed by scintigraphy, improved with time. Maximal tumour uptake occurred between 4 and 48 h. Dynamic and static scintigrams indicated some early sequestration of radiolabelled antibody by the liver. Tumours were surgically resected in seven patients at various intervals after antibody administration showing tissue to blood ratios increasing with time in all parts of the lesion (viable and necrotic tumour, cyst fluid), and in normal brain. The highest tissue to blood ratio in viable tumour was 5.1 at 16 days after injection. In tissues resected 2-3 days after injection there was relatively greater uptake in the viable tumour compared to necrotic tumour and cyst fluid. In contrast, tissues resected later (6-16 days) showed greater uptake in ischaemic tissue than viable tumour, suggesting diffusion was an important factor influencing tumour uptake. The amount of radioactivity per gram of tumour tissue was less than 0.005% of the injected dose. Future studies are needed using different antibodies, antibody fragments and additional methods of optimising delivery.
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