RADIOTOXICITY OF 67-GALLIUM ON MYELOID LEUKEMIC BLASTS

Promising clinical results are obtained with radiolabeled antibodies i n leukemia patients. (67)Gallium (Ga-67) is a radionuclide that accumu lates in many malignant tissues without need for a monoclonal antibody . For this reason, the use of Ga-67 as a therapeutic agent is appealin g. In the present we study, we report data about the radiotoxicity of Ga-67 on peripheral blast cells of 23 patients with acute myelogenous leukemia (AML) in vitro. Isolated blast cells were incubated for 4 day s with 0.74 MBq/ml (20 mu Ci/ml), 1.48 MBq/ml (40 mu Ci/ml) or 2.96 MB q/ml (80 mu Ci/ml) Ga-67. Compared with non-irradiated control cells p roliferation during incubation was almost abolished. Clonogenic surviv al was measured by a colony forming unit assay (CFU-assay). In 13 of t he 23 patients (56%) sufficient colony growth was observed for evaluat ion. The mean clonogenic survival of blasts after incubation with 0.74 MBq/ml, 1.48 MBq/ml and 2.96 MBq/ml Ga-67 was 22.5, 11.3 and 3.5%, re spectively. In some cases colony growth was completely abolished after incubation with only 0.74 MBq/ml Ga-67. No correlation was found betw een cellular Ga-67-uptake, (micro)dosimetry and transferrin receptor d ensity (CD-71) via which Ga-67 enters the cell. In vitro the blasts re ceived a dose of >10 Gy in 9 of the 2.96 MBq/ml, in 3 of the 1.48 MBq/ ml and in 2 of the 0.74 MBq/ml incubations. In one patient, even a rad iation dose >40 Gy was reached. Low dose rate irradiation is known to arrest cells in G2/M-phase of the cell cycle, but no such arrest was o bserved during incubation with Ga-67. Thus, Ga-67 induces clonogenic c ell death in leukemic blasts. Cellular uptake of Ga-67 in vitro varies between patients and can be very high in some patients. The easy avai lability, low costs and absence of immunological problems warrant furt her investigation of the therapeutic potential of Ga-67 in refractory or relapsed AML patients.