Abstract
Abstract Introduction Despite its desirable half-life and low energy Auger electrons that travel further than for other radionuclides, 67 Ga has been neglected as a therapeutic radionuclide. Here, 67 Ga is compared with Auger electron emitter 111 In as a potential therapeutic radionuclide. Methods Plasmid pBR322 studies allowed direct comparison between 67 Ga and 111 In (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 67 Ga and 111 In 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 67 Ga and was comparable to that caused by 111 In; 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 1.0Bq/cell for both 67 Ga and 111 In; the A 50 values determined by clonogenic assay were 0.7Bq/cell and 0.3Bq/cell for 111 In and 67 Ga respectively. At the concentrations required to achieve these uptake levels, non-internalized 67 Ga and 111 In caused no cellular toxicity. Qualitatively similar results were found for MDA-MB-231 and HCC1954 cells. Conclusion 67 Ga causes as much damage as 111 In to plasmid DNA in solution and shows similar toxicity as 111 In at equivalent internalized activity per cell. 67 Ga 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, 67 Ga could become a useful radionuclide with little healthy tissue toxicity in the arsenal of weapons for treating cancer.
Highlights
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
Radioisotopes emitting Auger electrons with a much shorter range (b1 μm) are being considered for targeted radionuclide therapy and could become useful tools in targeting micrometastases that play a detrimental role in tumor recurrence
In DU145 cells, a one-hour incubation with 111In-oxine or 67Ga-oxine allowed radionuclide binding at 60.6 ± 8.8% or 7.5 ± 1.3%, respectively (Fig. 3A)
Summary
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. 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. Radiopharmaceutical therapies, such as 131I–MIBG, anti-CD20 antibodies (labeled with 90Y or 131I), and 177Lu-Octreotate, have become standard in the clinic. These beta particle-emitting treatments, are generally not curative and can cause toxicity to healthy tissue due to the long range (up to 1 cm for 90Y) by high beta energies. Complimentary access to this article is available until the issue publishes online
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