Basis research and development of DNA-targeted radio-platinum agents for Auger electron cancer therapy

概要

Surgery, chemotherapy, and radiation therapy are widely used as cancer treatments. Surgery is the
first-choice approach in many cancer types; unfortunately, sometimes the patient's conditions, like the
malignant tumor type/size/location and the degree of metastasis/invasion, make a surgical treatment
insufficient or incapable for the patients. To destroy as many cancer cells as possible, chemotherapy
and/or radiation therapy are mostly applied in addition to or instead of surgical approaches.1
Chemotherapy is commonly performed before and/or after surgery to kill even invisible cancer cells
that cannot be removed by surgery throughout the body. A variety of anticancer drugs and regimens
are now being developed to achieve high therapeutic effects even against drug-resistant cancers while
minimizing adverse effects. Radiation therapy is also essential in clinics as a low-invasive treatment
applicable to various cancers. The therapeutic effect of radiotherapy is normally based on the irradiated
dose on tumors, where the malignant tissues need to be irradiated sufficiently keeping the normal
tissue dose as low as possible. Effective and uniform irradiation of the tumors leads to a reliable
therapeutic efficacy derived from physio-chemical damage. The well-established external
radiotherapy using γ-rays, X-rays, or particle beams like protons and heavier ions is employed in
radiation-sensitive cancers, pre/post-treatment of large tumors before/after surgery, and situations
where normal tissues must be maintained as much as possible.2 There are other radiotherapies, like
brachytherapy, using a sealed radiation source placed inside or next to tumors,3 or boron neutron
capture therapy (BNCT) using alpha-rays emitted from neutron capture reaction of boronic agents.4
However, these external radiation therapy approaches are available only for the tumors of which the
location is defined.
Radiopharmaceuticals have been widely used in single photon emission computed
tomography (SPECT) and positron emission tomography (PET) techniques as a non-invasive imaging
modality in diagnosis procedures,5 and also used for targeted radionuclide therapy (TRT) in therapeutic
procedures. As an internal radiotherapy using radiopharmaceuticals, TRT is emerging because it can
target even invisible cancer cells. In TRT, targeted malignant tissues are irradiated and damaged
efficiently with short-range radiation emitted from radionuclides in low chemical doses (ng–µg). An
ideal delivery system of radionuclides to tumors potentially achieves a low-invasive treatment
modality to target and treat all of the cancer cells throughout the body.
β--rays, α-rays, or Auger electrons are the candidate sources for TRT (Table 1 and Fig. ...

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