title: Re-assessing gallium-67 as a therapeutic radionuclide.
abstract: BACKGROUND
  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 emitter111In as a potential therapeutic radionuclide.
  
  
  METHODS
  Plasmid pBR322 studies allowed direct comparison between67Ga and111In (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-internalized67Ga and111In 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 by67Ga and was comparable to that caused by111In; it was reduced in the presence of EDTA, DTPA and DMSO. The A50values (internalized activity of oxine complexes per cell required to kill 50% of cells) as determined by trypan blue staining was 1.0Bq/cell for both67Ga and111In; the A50values determined by clonogenic assay were 0.7Bq/cell and 0.3Bq/cell for111In and67Ga respectively. At the concentrations required to achieve these uptake levels, non-internalized67Ga and111In caused no cellular toxicity. Qualitatively similar results were found for MDA-MB-231 and HCC1954 cells.
  
  
  CONCLUSIONS
  67Ga causes as much damage as111In to plasmid DNA in solution and shows similar toxicity as111In at equivalent internalized activity per cell.67Ga therefore deserves further evaluation for radionuclide therapy.
  
  
  CONCLUSIONS
  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.
authors.affiliation: King's College London, Department of Imaging Chemistry and Biology, St. Thomas' Hospital, London, SE1 7EH, UK.
authors.forename: Muhamad F Bin
authors.initials: MF
authors.lastname: Othman
authors.affiliation: King's College London, Department of Imaging Chemistry and Biology, St. Thomas' Hospital, London, SE1 7EH, UK.
authors.forename: Nabil R
authors.initials: NR
authors.lastname: Mitry
authors.affiliation: Guy's & St Thomas' NHS Foundation Trust, Nuclear Medicine Department, London, SE1 9RT, UK.
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Lewington
authors.affiliation: King's College London, Department of Imaging Chemistry and Biology, St. Thomas' Hospital, London, SE1 7EH, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Blower
authors.affiliation: King's College London, Department of Imaging Chemistry and Biology, St. Thomas' Hospital, London, SE1 7EH, UK. Electronic address: samantha.terry@kcl.ac.uk.
authors.forename: Samantha Y A
authors.initials: SY
authors.lastname: Terry
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D005710:Gallium Radioisotopes / Q000627:therapeutic use*; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D015125:Oxyquinoline / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000473:pathology; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D005710:Gallium Radioisotopes; D019275:Radiopharmaceuticals; D015125:Oxyquinoline
keywords: Auger electrons; Clonogenic assay; Gallium-67; Radionuclide therapy