کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5520028 | 1544558 | 2017 | 17 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Radioimmunotherapy of cancer with high linear energy transfer (LET) radiation delivered by radionuclides emitting α-particles or Auger electrons Radioimmunotherapy of cancer with high linear energy transfer (LET) radiation delivered by radionuclides emitting α-particles or Auger electrons](/preview/png/5520028.png)
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 as 131I, 177Lu or 90Y which have been commonly conjugated to the mAbs, due to their low linear energy transfer (LET = 0.1-1.0 keV/μm). Furthermore, since the β-particles have a 2-10 mm 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 or 211At) or Auger electron-emitters (e.g. 111In, 67Ga, 123I or 125I) would increase the potency of RIT due to their high LET (50-230 keV/μm and 4 to 26 keV/μm, respectively). In addition, α-particles have a range in tissues of 28-100 μm 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.
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Journal: Advanced Drug Delivery Reviews - Volume 109, 15 January 2017, Pages 102-118