Re-assessing gallium-67 as a therapeutic radionuclide

Introduction: Despite its desirable half-life and low energy Auger electrons that travel further than for other radio-nuclides, Ga-67 has been neglected as a therapeutic radionuclide. Here, Ga-67 is compared with Auger electron emitter In-111 as a potential therapeutic radionuclide. Methods: Plasmid pBR322 studies allowed direct comparison between Ga-67 and In-111 (1 MBq) in causing DNA damage, including the effect of chelators (EDTA and DTPA) and the effects of a free radical scavenger (DMSO). The cytotoxicity of internalized (by means of delivery in the form of oxine complexes) and non -internalized Ga-67 and In-111 was measured in DU145 prostate cancer cells after a one-hour incubation using cell viability (trypan blue) and clonogenic studies. MDA-MB-231 and HCC1954 cells were also used. Results: Plasmid DNA damage was caused by Ga-67 and was comparable to that caused by In-111; it was reduced in the presence of EDTA, DTPA and DMSO. The A(50) values (internalized activity of oxine complexes per cell required to kill 50% of cells) as determined by trypan blue staining was 1.0 Bq/cell for both Ga-67 and In-111; the A(50) values determined by clonogenic assay were 0.7 Bq/cell and 0.3 Bq/cell for In-111 and Ga-67 respectively. At the concentrations required to achieve these uptake levels, non-internalized 67Ga and In-111 caused no cellular toxicity. Qualitatively similar results were found for MDA-MB-231 and HCC1954 cells. Conclusion: Ga-67 causes as much damage as In-111 to plasmid DNA in solution and shows similar toxicity as In-111 at equivalent internalized activity per cell. Ga-67 therefore deserves further evaluation for radionuclide therapy. Advances in knowledge and implications for patient care: The data presented here is at the basic level of science. If future in vivo and clinical studies are successful, Ga-67 could become a useful radionuclide with little healthy tissue toxicity in the arsenal of weapons for treating cancer. (C) 2016 The Authors. Published by Elsevier Inc.