Radioimunotargetting in India with special reference to Hepatic metastases: Recent Advances

摘要

Our experience in using a pancarcinoma antibody M3 directed against the Tissue PolypeptidernSpecific Antigen in radioimunotargetting solid tumours both in experimental animals and in clinical subjectsrnis described using a variety of labels: Technetium 99m, Iodine 131 and Gold 199, the last only inrnexperimental animals. We developed a method of sharply reducing nonspecific reticuloendothelial uptakernusing unlabelled nonspecific human gammaglobulin both in animals and humans, with potential significancernfor immunotherapy ,whether with radiolabelled antibodies, or unlabelled, or with nonradioactive labels, forrnconserving scarce and expensive antibodies and improving therapeutic response. We also describe our use ofrnthis antibody for radioimmunoscintigraphy and radioimmunotherapy for hepatic metastases in subjects inrnwhom the primary lesion had been resected, but who had now presented with multiple hepatic metastases butrnwere considered inoperable or unsuited for radoiofrequency ablation. Doses of 25-50 mg antibody bearing 50-rn150 mCi of radioiodine were well tolerated without significant adverse effects on haematological (red cell,rnwhite cell or platelet count),hepatic(Serum Glutamic Transaminase levels) or renal (serum creatinine)rnparameters. Dramatic improvement in pain was observed with size stabilization of the liver metastases forrnperiods as long as one year in 4 out of 6 patients, but metastases did not disappear. In some cases somernmetastases shrank but new lesions appeared, suggesting the selection of resistant cell populations. Repeatedrnadministration of these murine antibodies was limited by the appearance of serological and/or clinicalrnevidence of Human Anti Mouse Antibody reactions. Possible solutions under exploration includernhumanization or other modification of the anticancer antibodies, immunosuppression with agents such asrncorticosteroids, and combining high dose single shot therapy with rescue bone marrow transplantation. Itrnappears logical also to use radiolabelled antibodies in the immediate post surgical ablation scenario torneliminate or forestall micrometastases rather than in patients in whom massive multiple metastases havernalready developed.