No abstract available

[en] The kinetics of uptake and of radiotoxicity of chromium-51, an Auger-electron emitter, have been studied in V79 lung fibroblasts of the Chinese hamster. Intracellular radioactivity was directly proportional to the incubation period and to the extracellular concentration of the Cr-51. About 14% of the cellular activity was associated with the nucleus, whereas approximately 2% was guanidine-precipitable and therefore bound to DNA. The growth rate of V79 cells was slowed following intracellular incorporation of Cr-51. The cell-survival curve, in terms of colony-forming ability, was of the low-LET type, with a D₃₇ of 6.2 pCi/cell. Theoretical dosimetric estimates indicate that, under the given experimental conditions, the mean lethal dose to the cell nucleus was 870 rad

[en] Iodine-125, in the form of 5-(¹²⁵I)-iododeoxyuridine, has been the subject of many investigations because of the extreme effectiveness of this Auger electron emitter in causing biological effects at the molecular and cellular levels. However, no study has been reported on the kinetics of the radiotoxicity and its relation to microdosimetric considerations. The authors examined the effects of varying the extracellular radioactive concentration, incubation period, and specific activity of ¹²⁵IUdR on the incorporation of this radionuclide into the DNA of Chinese hamster V79 lung fibroblasts. The experimental results were related to the consequent alterations in the growth rate and survival and used to calculate the total number of decays occurring in the cell nucleus. The authors' data indicate that a) the mean lethal uptake at 37% survival (D₃₇) is 0.035 rhoCicell; b) the total number of disintegrations is about 100cell; and c) using the Auger electron energy deposition patterns of ¹²⁵I, the average energy deposited in the nucleus per ¹²⁵I decay is estimated to be 11.2 keV. Since the nuclear volume of V79 cells is 268 μ³, the average D₃₇ dose to the nucleus is about 67 rad; for the same cell line, the D₃₇ for x-rays is 580 rad. Thus, ¹²⁵I is about 8 times more effective than x-ray in causing the same biological end point

[en] The cellular distribution of tissue-incorporated radionuclides has generally been neglected in the dosimetry of internal emitters. Traditional dosimetry assumes homogeneous distribution of radionuclides in organs of interest, while presuming that the ranges of particulate radiations are large relative to typical cell diameters. The macroscopic distribution of dose thus calculated has generally served as a sufficient approximation for the energy deposited within radiosensitive sites. However, with the increasing utilization of intracellular agents, such as thallium-201, it has become necessary to examine the microscopic distribution of energy at the cellular level. This is particularly important in the instance of radionuclides that decay by electron capture or by internal conversion with the release of Auger and Coster-Kronig electrons. In many instances, these electrons are released as a dense shower of low-energy particles with ranges of subcellular dimensions. The high electron density in the immediate vicinity of the decaying atom produces a focal deposition of energy that far exceeds the average dose taken over several cell diameters. These studies point out the increasing need to take into account the microscopic distribution of dose on the cellular level as radionuclides distributed in cells become more commonplace, especially if the decay involves electron capture or internal conversion. As radiotracers are developed for the measurement of intracellular functions these factors should be given greater consideration. 16 references, 5 figures, 5 tables

[en] Experimental data are presented which clearly demonstrate that the PAC method may be applied to a wide range of macromolecular systems by an appropriate choice of the probe and that biophysically meaningful results are indeed obtained through PAC. (Auth.)

[en] The extreme radiotoxicity of DNA incorporated iodine-125 has aroused interest in the biologic and dosimetric implications of tissue incorporated Auger electron emitters. These effects are not readily predictable because of their dependence on the intracellular distribution of the radionuclide and the energy spectra of the Auger electrons. We have investigated the kinetics of cellular uptake, distribution, and radiotoxicity of the Auger electron emitters ²⁰¹T1, ¹²⁵I, ¹²³I, ⁷⁷Br, ⁷⁵Se and ⁵¹Cr in cultured mammalian cells. The experimental data and theoretical estimates of the average Auger electron spectra have been used to interpret the biologic effect of Auger electron emitters. Five or more Auger electrons on the average are emitted per decay of each radionuclide depositing substantial energy (≥200 eV) in a 5 nm sphere of biologically equivalent matter. The radiotoxicity of these nuclides is dependent on their proximity to nuclear DNA. A correlation between the reciprocal of the mean lethal uptake at 37% survival and the locally deposited energies could only be demonstrated for the DNA-incorporated ¹²⁵I, ¹²³I, and ⁷⁷Br. These observations indicate the importance of intracelular distribution and microdosimetric considerations for tissue incorporated Auger electron emitters

[en] Monte Carlo calculations are performed of the physical and chemical interactions in liquid water by electrons produced during Auger cascades resulting from the decay of various radionuclides. Estimates are also made of the number of direct physical and indirect chemical interactions that would be produced on DNA located near the decay site. 13 refs., 8 figs

[en] Chromium-51 decays 100% by electron capture with the emission of 320 KeV γ-rays (9.9%) and 4.95 KeV X-rays. The inner atomic shell vacancies produced by these processes initiate vacancy cascades and the emission of numerous electrons. Theoretical estimates indicate that several of these electrons have very low energies (15-100 eV) with extremely short ranges (<50 A) in biological matter. Therefore, provided that the locally absorbed energy density is sufficient to produce molecular lesions, the damage produced may exceed repair capability and result in cell death. Uptake and radiotoxicity of /sup 51/Cr was studied in Chinese hamster V79 cells. Cellular radioactivity was directly proportional to the incubation period and the extracellular radioactive concentration. Of the 14% of the nucleus-associated activity, --2% was guanidine precipitable and therefore DNA-bound. The survival curve was of the low LET-type with a D/sub 37/ of 6.2 rhoCi/cell. Theoretical dose estimates indicate that for the 18 hr exposure, the dose to the cell is identical to the X-ray D/sub 37/ dose of 580 rads while classical MIRD dose calculations grossly underestimate the cellular dose (2-3 rads/cell). The toxicity and microscopic dosimetry of this radionuclide are compared with other Auger emitters

[en] Cis-Platinum is widely used in chemotherapy of cancer. Its usefulness is limited by its chemotoxic effects. The action of this drug involves its binding to DNA base sequences. The overwhelming evidence for the cytocidal effects of DNA-incorporated ¹²⁵I through localized irradiation of intranuclear radiosensitive sites by the numerous low energy Auger electrons from its decay suggests the interesting prospect of chemo-Auger combination therapy using cis-Pt labeled with suitable radionuclides. In this approach, the localized action of Auger electrons augments the chemical action of cis-Pt for cell killing. Accordingly, possibilities exist for a reduction of the chemotoxicity of the drug. The radionuclides /sup 195m/Pt and /sup 193m/Pt are natural candidates in this regard since both are prolific emitters of low energy Auger electrons by virtue of their decay modes. Preliminary studies with cis-/sup 195m/Pt on experimental mouse tumor models are encouraging. The problem with /sup 195m/Pt is its low specific activity. In contrast, /sup 193m/Pt can be produced at a much higher specific activity, even carrier-free, compared to /sup 195m/Pt. Monte Carlo calculations show that about 25 Auger electrons are to be expected per decay of /sup 193m/Pt. The microdosimetry of these electrons indicates that the localized absorbed energy density around the decay site is more than in the case of ¹²⁵I. These considerations point to the promise of cis-/sup 193m/Pt fr chemo-Auger combination therapy. The cellular dosimetry of /sup 193m/Pt, localized on the surfaces of cells, is also discussed in the context of the current interest in radioimmunotherapy. 4 references, 4 figures, 6 tables

[en] NQR Zeeman effect studies in 2, 4, 6 Tribromophenyl-p-toluene Sulfonate for ⁷⁹Br isotope were carried out using single crystals. The value of the asymmetry parameter and the directions of the principal field gradient X, Y, Z axes were determined. The values of the various contributions to the bond character are calculated. (auth.)