Auger electron emission application of radionuclide targeted therapy

        Auger electron cytotoxicity and its application in targeted radiotherapy within the application, especially for 125I and 125I-Idoxuridine (IUdR) of long-term study, so that people's understanding in this area has been a breakthrough. International Atomic Energy Agency (IAEA) in 1976 launched the international cooperation in research projects to study the 125I-UdR treatment of human tumor mechanisms, the feasibility and practical value [1]. J Nucl Med (USA) in 1996 reported supplement the system in this field are reviewed.

        1, Auger electron emission of radionuclides

        Auger electron emission of radionuclides a lot can be divided into three categories [2]: ① γ -ray emission Auger electron emission at the same time there are 51Cr, 67Ga, 75Sr, 80Brm, 99Tcm, 114Inm,

        115 Inm, 123I, 125I, 193Ptm and 195Ptm, etc.; ② α -ray emission Auger electron emission at the same time there are 212Bi, 211At, and 255Fm; ③ positron emission Auger electron emission at the same time there are 73Se, 94Tc, and 124I.

        2, Auger electron physics properties

        Of radionuclides in the electron capture or internal conversion in the process of Auger electron emission [2]. Decay of different radionuclides emitted Auger electron has a different energy, most of which Auger electron energy of 20 ~ 500 eV, within the range of biological tissue 1 ~ 10 nm, linear energy transfer (LET) of 10 ~ 25 keV / μ m, a high-LET, and LET α particles close to [3]. Such as the decay of 125I is divided into two steps, the first step is an electron-trapping, the first step 2 is an inner transformation, in this two-step process, respectively, the same amount of emitted Auger electron, a total of 22. The 123I was first through the electron capture Auger electron emission 11, and then fired through the isomer γ -photon energy conversion. Therefore, 125I decay time the number of electrons produced by Auger 2 times 123I. Each other radioactive nuclides produced by Auger decay of the number of electrons: 99Tcm for 4, 111In for 8, 201Tl to 20. 125I Auger electron emitted per decay of the absorbed dose of 0.74 ~ 100 Gy [2,3].

        3, Auger electron mechanism of cellular toxicity

        1. In vitro and in vivo, a large number of experimental animals and humans have confirmed that Auger electron emission radionuclide marker into the vector parameter S-phase cells DNA, radionuclide decay, issued by the Auger electron by its high-LET interrupted DNA chain, destruction of the genetic material of cells, , killing cells. As the range of Auger electrons very short (<10 nm), equivalent to only 6 base pairs of the distance, so the location of nuclides decay is interrupted by the location of DNA. This is the most important role of Auger electron mechanism [4].

        2. Have been found to use of Cysteamine (MEA), VC and other chemical protective agents can reduce the Auger electron cytotoxicity tests showed that decay near the OH, H, H3O and other free radicals at high concentrations, with the location of the distance from the decay of increase in concentration decreased. Therefore proposed that the mechanism of Auger electron addition to the direct role of DNA damage should also include the ionization caused by free radicals generated by the increase in indirect cytotoxicity [3].

        3. Beckmann et al [5] to 125I-estradiol (E) and human breast cancer cell lines (MCF-7) The experimental results show that, 125I-E and chromosome of estrogen receptor binding, the same chromosome can break, lethal cells, suggesting that receptor-ligand binding is not cell cycle-dependent problems.

        4, carrier

        1. IUdR is the most studied, the most widely used 125I, 123I and 77Br carrier thymidine (TdR) 5-position of the methyl was replaced by an iodine atom, resulting in an IUdR. In this position of the methyl and iodine atom have similar van der Chinese power, so the biological behavior of TdR and IUdR very similar to [6]. Participation by TdR or IUdR into the DNA, cell division and nucleic acid metabolism of the proliferation is already very mature technology. Experimental results show that, IUdR can only reference into the S phase cell DNA. Participation in vitro cell culture IUdR into the cell vulnerable to DNA, participation into the medium by adding volume and proportional to the concentration of IUdR. Sastry et al [3] with the V79 cell line, culture medium by adding 125I-UdR, cultured 18 h after the radiation is measured inside the cell culture medium for 1 800 times. With the normal W138 and Hela cell line experiments, and use rice - Bangladesh was calculated as 125I-UdR into DNA of the Vmax parameters for the 4.424 * 10-18 mol / min, K = 3.717 * 10-6 mol. Pretty too: If an S period, all of the TdR were 125I-UdR replacement, CHO cells have 6.6 * 10-12g DNA, 6.1 * 109 base pairs (bp), of which 25% of the bp if the TdR, that there is 1.525 * 109 125I-UdR elements in a parameter into the S period of DNA. If an S period of 7

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