HIGH-DOSE GA-67 THERAPY IN PATIENTS WITH RELAPSED ACUTE-LEUKEMIA - A FEASIBILITY STUDY

Gallium-67 (Ga-67) accumulates in malignant tissues via the transferri n receptor without need for a monoclonal antibody and emits cytotoxic low-energy electrons. In this study we investigated the feasibility, p harmacokinetics, toxicity and preliminary efficiency of high-dose Ga-6 7 injected intravenously (i.v.) in patients with acute leukaemia not r esponding to conventional therapy. Twelve doses of 36-105 mCi of Galli um(67) citrate were administered as a push injection to eight patients with resistant leukaemia in a pilot study. All five patients with acu te myeloid leukaemia (AML) and three patients with acute lymphoblastic leukaemia (ALL) had resistant disease or resistant relapse. No (sub)a cute toxicity was observed. Independent of the administered dose, whol e-blood radioactivity levels 10 min after administration measured only 1.25 +/- 1.39 mu Ci ml(-1), indicating a large volume of distribution . Urine excretion in the first 24 h ranged from 18% to 51.5% (median 2 9.5%) of the administered dose. Cellular uptake of Ga-67 was less than in previous in vitro studies. Whole-body radiation dose was estimated to be 0.25 +/- 0.03 cGy mCi L. Red marrow dose was estimated to be be tween 0.18 +/- 0.02 and 0.97 +/- 0.12 cGy mCi(-1). One definite respon se was observed in an ALL patient with disappearance of skin lesions, normalisation of the enlarged spleen and profound leucopenia. Three ot her patients showed transient reductions in white blood cell counts wi thout disappearance of blasts from the peripheral blood. We conclude t hat high-dose i.v. Ga-67 can be safely administered but that the uptak e of Ga-67 in blast cells must increase to make Ga-67 therapeutically useful in patients with relapsed leukaemia.