Re-assessing gallium-67 as a therapeutic radionuclide

Abstract

Introduction: Despite its desirable half-life and low energy Auger electrons that travel further than for other radionuclides, ⁶⁷Ga has been neglected as a therapeutic radionuclide. Here, ⁶⁷Ga is compared with Auger electron emitter ¹¹¹In as a potential therapeutic radionuclide.

Methods: Plasmid pBR322 studies allowed direct comparison between ⁶⁷Ga and ¹¹¹In (1MBq) 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 ⁶⁷Ga and ¹¹¹In 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 ⁶⁷Ga and was comparable to that caused by ¹¹¹In; it was reduced in the presence of EDTA, DTPA and DMSO. The A₅₀ values (internalized activity of oxine complexes per cell required to kill 50% of cells) as determined by trypan blue staining was 1.0Bq/cell for both ⁶⁷Ga and ¹¹¹In; the A₅₀ values determined by clonogenic assay were 0.7Bq/cell and 0.3Bq/cell for ¹¹¹In and ⁶⁷Ga respectively. At the concentrations required to achieve these uptake levels, non-internalized ⁶⁷Ga and ¹¹¹In caused no cellular toxicity. Qualitatively similar results were found for MDA-MB-231 and HCC1954 cells.

Conclusion: ⁶⁷Ga causes as much damage as ¹¹¹In to plasmid DNA in solution and shows similar toxicity as ¹¹¹In at equivalent internalized activity per cell. ⁶⁷Ga 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, ⁶⁷Ga could become a useful radionuclide with little healthy tissue toxicity in the arsenal of weapons for treating cancer.

Keywords: Auger electrons; Clonogenic assay; Gallium-67; Radionuclide therapy.