title: Radioimmunotherapy of cancer with high linear energy transfer (LET) radiation delivered by radionuclides emitting α-particles or Auger electrons.
abstract: Radioimmunotherapy (RIT) aims to selectively deliver radionuclides emitting α-particles, β-particles or Auger electrons to tumors by conjugation to monoclonal antibodies (mAbs) that recognize tumor-associated antigens/receptors. The approach has been most successful for treatment of non-Hodgkin's B-cell lymphoma but challenges have been encountered in extending these promising results to the treatment of solid malignancies. These challenges include the low potency of β-particle emitters such as131I,177Lu or90Y which have been commonly conjugated to the mAbs, due to their low linear energy transfer (LET=0.1-1.0keV/μm). Furthermore, since the β-particles have a 2-10mm range, there has been dose-limiting non-specific toxicity to hematopoietic stem cells in the bone marrow (BM) due to the cross-fire effect. Conjugation of mAbs to α-particle-emitters (e.g.225Ac,213Bi,212Pb or211At) or Auger electron-emitters (e.g.111In,67Ga,123I or125I) would increase the potency of RIT due to their high LET (50-230keV/μm and 4 to 26keV/μm, respectively). In addition, α-particles have a range in tissues of 28-100μm and Auger electrons are nanometer in range which greatly reduces or eliminates the cross-fire effect compared to β-particles, potentially reducing their non-specific toxicity to the BM. In this review, we describe the results of preclinical and clinical studies of RIT of cancer using radioimmunoconjugates emitting α-particles or Auger electrons, and discuss the potential of these high LET forms of radiation to improve the outcome of cancer patients.
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Aghevlian
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Boyle
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada; Department of Medical Imaging, University of Toronto, Toronto, ON, Canada; Toronto General Research Institute and Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada. Electronic address: raymond.reilly@utoronto.ca.
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Reilly
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use; D000818:Animals; D004583:Electrons / Q000627:therapeutic use; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D018499:Linear Energy Transfer; D009369:Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000009:adverse effects; D011868:Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018796:Immunoconjugates; D011868:Radioisotopes
keywords: Auger electrons; Cancer; Monoclonal antibodies; Radiation treatment; Radioimmunotherapy; α-Particles