Utility of γH2AX as a Molecular Marker of DNA Double-Strand Breaks in Nuclear Medicine: Applications to Radionuclide Therapy Employing Auger Electron-Emitting Isotopes

Li-Jeen      Mah; Christian      Orlowski; Katherine      Ververis; Assam      El-Osta; Tom      C. Karagiannis

Abstract

There is an intense interest in the development of radiopharmaceuticals for cancer therapy. In particular, radiopharmaceuticals which involve targeting radionuclides specifically to cancer cells with the use of monoclonal antibodies (radioimmunotherapy) or peptides (targeted radiotherapy) are being widely investigated. For example, the ultra-short range Auger electron-emitting isotopes, which are discussed in this review, are being considered in the context of DNAtargeted radiotherapy. The efficient quantitative evaluation of the levels of damage caused by such potential radiopharmaceuticals is required for assessment of therapeutic efficacy and determination of relevant doses for successful treatment. The DNA double-strand break surrogate marker, γH2AX, has emerged as a useful biomonitor of damage and thus effectiveness of treatment, offering a highly specific and sensitive means of assessment. This review will cover the potential applications of γH2AX in nuclear medicine, in particular radionuclide therapy.

Keywords: γH2AX, double-strand breaks, targeted radiotherapy, radionuclides, auger emitters, DNA DAMAGE, H2AX INDUCTION, SPATIAL AND TEMPORAL DISTRIBUTION, ELECTRON EMITTING ISOTOPES, EFFECTS OF OTHER HIGH LET RADIONUCLIDES