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Re-assessing gallium-67 as a therapeutic radionuclide

Research output: Contribution to journalArticlepeer-review

M.F.B. Othman, N.R. Mitry, V.J. Lewington, P.J. Blower, S.Y.A. Terry

Original languageEnglish
Pages (from-to)12-18
Number of pages7
JournalNuclear Medicine and Biology
Volume46
Early online date29 Oct 2016
DOIs
Accepted/In press6 Oct 2016
E-pub ahead of print29 Oct 2016
PublishedMar 2017

Bibliographical note

Export Date: 14 February 2017

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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 (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 internalised (by means of delivery in the form of oxine complexes) and non-internalised 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 (internalised 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 to achieve these uptake levels, non-internalised 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 internalised 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.

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