Endocrine Abstracts

Background: Despite its desirable half-life and high-energy Auger electrons, ⁶⁷Ga has been neglected as a therapeutic Auger electron emitter, due in part to lack of suitable chelators and targeting molecules.

Objective: Here, ⁶⁷Ga is compared with Auger electron emitter ¹¹¹In as a therapeutic radionuclide in prostate cancer and breast cancer cell lines.

Method: Plasmid pBR322 studies allowed direct comparison between ⁶⁷Ga and ¹¹¹In (1 MBq) in causing DNA damage, including the effect of chelators EDTA and DTPA and the effects of free radical scavenger DMSO. The cytotoxicity of internalized (using oxine) and non-internalized ⁶⁷Ga and ¹¹¹In was measured in cancer cells after a one-hour incubation using cell viability and clonogenic studies.

Results: Plasmid DNA damage caused by ⁶⁷Ga was comparable to ¹¹¹In and 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 1.0 Bq/cell for both ⁶⁷Ga and ¹¹¹In; the A₅₀ values determined by clonogenic assay were 0.7 Bq/cell and 0.3 Bq/cell for ¹¹¹In and ⁶⁷Ga respectively. At the concentrations required achieving these uptake levels, non-internalized ⁶⁷Ga and ¹¹¹In caused no cellular toxicity.

Conclusion: ⁶⁷Ga causes as much damage as ¹¹¹In to plasmid DNA in solution and is more toxic than ¹¹¹In at equivalent internalized activity per cell in the cell types studied. ⁶⁷Ga therefore deserves further evaluation for radionuclide therapy.