[The contribution of artificial radioisotopes of gold Au 198 to the treatment of cancer of the ovaries].
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Cytostatic long-term treatment for about 36 months was administered to 18 children with acute lymphatic leukaemia who were in long-term remission (43-98 months). Prophylaxis of meningosis involved intrathecal 198Au colloid and methotrexate. Seven recurrences occurred during the long-term remissions: the bone marrow was involved six times, leukaemic meningosis occurred once. Five out of seven recurrences occurred within one year of cessation of treatment. There were no complications induced by intrathecal radio-gold, such as the apathy syndrome or leukoencephalopathy. Intrathecal methotrexate led to side effects before administration of radio-gold: encephalopathy twice, paraplegia once. Symptoms regressed completely in two children, one child with encephalopathy continues to have symptoms. All three children were given 198Au colloid intrathecally thereafter which was tolerated very well. 198Au colloid represents an alternative for prophylaxis of meningosis with 60Co telecobalt irradiation in leukaemias and non-Hodgkin lymphomas in childhood.
High specific activity radiopharmaceuticals cannot readily be produced by (n, gamma) reactions in nuclear reactors, because the great abundance of parent atoms remaining have the same chemical characteristics as the produced isotope. We have investigated the effectiveness of using recoil atom collection methods for separating the produced radioisotope. Gold-198, produced from isotopically pure (natural) gold-197, was chosen for these experiments, which were run in the high flux (approximately 10(14) n/cm2 s thermal flux) of the reflector of the University of Missouri Research Reactor. Seven separate experiments were run, with a 2 mm separation between the emitter and the collector. Collection efficiencies were only a few percent of the radioisotope atoms produced in the top atomic layer of the emitter, instead of the 30% range anticipated. Furthermore, the collected radioisotope, instead of being nearly pure, contained a large quantity of the parent. Unless the reason for the "contamination" of product with the parent can be reduced by several orders of magnitude, this "surface hot atom recoil" method appears to offer no practical application for nuclear medicine isotope production.
Advances in imaging technology and implant technique have led to the resurgent interest and practice of brachytherapy for the treatment of prostate cancer. Brachytherapy is a form of radiation treatment in which radioactive sources are placed directly into the tumor; it offers the advantage of maximizing the radiation dose delivered to the tumor while sparing the adjacent normal tissue. Permanent implants have become an important component of radiation delivery. Interstitial gold radioisotope (Au-198) implants for prostate cancer were introduced at Baylor College of Medicine in 1965. The rationale for using Au-198, instead of the two most commonly used radioisotopes, Palladium-103 (Pd-103) and Iodine-125 (I-125), is discussed, and the Baylor implant technique is compared to that used in other centers. Retrospective review divides the patient population into pre-ultrasound versus post-ultrasound eras. Dosimetric calculation and disease control with the Au-198 seed implant for prostatic cancer are reviewed for the two different eras; toxicity is evaluated in the post-ultrasound era only. In the pre-ultrasound era, 510 patients were treated with pelvic lymph node sampling and gold seed insertion of the prostate followed by external beam radiation. In the post-ultrasound era, 54 patients were treated definitively with ultrasound-guided transperineal Au-198 implant followed by external beam irradiation. A small group of 30 patients in the post-ultrasound era were evaluated for the efficacy of Au-198 re-implantation for locally recurrent disease.
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The distribution of gold, copper and zinc in the livers and kidneys of female rats and hamsters was determined after intraperitoneal injection of sodium [195Au]-aurothiomalate. After five doses of sodium [195Au]-aurothiomalate (1 mg Au(I) per kg body weight), the hepatic and renal concentrations of Au were greater in rats than in hamsters. In the former species, treatment with the Au(I)-compound led to an increase in the Cu-concentration of the kidney and to the synthesis of a (Cu, Au)-metallothionein. In either species binding of Au to the hepatic metallothionein was insignificant. The renal (Cu, Au)-metallothionein from the sodium [195Au]-aurothiomalate-treated rat appeared to be extremely heterogeneous and was resolved into at least four components on ion exchange chromatography.
The tissue distribution of Sc-46, Mn-54, Zn-65, In-111 and Au-195 were studied in a rat hepatoma model at various time intervals over a 96 h period. The tumor localizing properties of these isotopes were evaluated by examining their incorporation and clearance from viable and nonviable tumor tissue and determining the critical tissue ratios formed with blood and muscle. In general, the results showed greater uptake in viable than nonviable tumor tissue at early time periods (4-24 h). By 96 h, however, the activity remaining in the nonviable tumor tissue exceeded the quantity in viable tumor tissue. This trend was previously noted for Ga-67. When compared with Ga-67, only Mn-54 among the isotopes studied showed remarkably higher viable tumor/blood ratios (4-24 h, 45:1-83:1 respectively). Manganese-54 also showed highly significant accumulation in cardiac muscle with a heart/blood ratio at 4 h superior to comparable values previously reported for Cs-137 and Tl-201. It is suggested that tumor and heart imaging may be feasible utilizing radioactive manganese (Mn-51 or Mn-52) with the new positron imaging systems.
The authors examined 40 patients with Hodgkin's lymphoma suspected from the localization of the process in mediastinum. They used X-ray investigation, radioisotope lung perfusion, radiogold-colloid lymphography and 67Ga-citrate scintigraphy. They found that, when the disease was diagnosed, X-ray examinations including tomography and lung perfusion gave reliable information in only half the cases whereas the other two nuclear medical methods showed positive results in 88% and 82%, respectively. In the diagnosis of relapse, the yield of these former methods was substantially higher, between 82--90%.
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The effects of the antiarthritic drugs aurothiomalate (AuTm), aurothioglucose (AuTg), auranofin, its metabolite triethylphosphinegold(I)thioglucose (Et3PAuTg), and several related complexes on the growth of Pseudomonas putida were studied. Two strains were used, one of which (BK135) was more sensitive to Et3PAuTg (tolerant up to 4 microM) than the other (BK403; tolerant to at least 500 microM). Gold thiolate complexes and thiolate ligands alone had little effect on growth. Gold phosphine complexes increased the length of the lag phase of growth and reduced oxygen uptake. Marked changes in cellular morphology were determined by electron microscopy. Copper(II) compounds and aurothiomalate were synergistic in their growth inhibitory effects towards these bacteria. Experiments with 195Au suggested that a mechanism does not exist for the short term (minutes) uptake of gold by sensitive or resistant bacteria, but the resistant strain appeared to limit gold uptake over a longer term (hours).
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Radionuclides with medium energy beta emission and a several day half-life have often been viewed as attractive candidates for radioimmunotherapy. Among the most promising in this category are 47Sc, 67Cu, 153Sm, 188Re, and 199Au. The production of 67Cu, 153Sm, 199Au at BNL is summarized and the development of the latest candidate for this application, 47Sc, is described in detail. We also summarize the development of another important therapeutic radionuclide, 117mSn for bone pain palliation.
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Simple analytical functions derived from our point source Monte Carlo calculations on the combined attenuation and scatter factor, B exp(-mu r), for 60Co, 137Cs, 198Au, 192Ir, 241Am, 125I (models 6702 and 6711) brachytherapy sources and the nuclide 99Tcm, for water spherical geometries of radii R = 15 and 20 cm, are presented. Our results for the broadly used 60Co, 137Cs, 198Au and 192Ir brachytherapy sources can be compared directly and found in excellent agreement with the widely accepted data of Meisberger et al in the limited distance range for which the latter are valid. Our data, however, can be used with high accuracy outside this distance range. Many discrepancies observed among different data sets available in recent literature are attributable to differences in geometries used. The results for the recently introduced 241Am source are very dissimilar to those produced by any other currently used brachytherapy source. Dose rate distributions, based on the above simple functions, are proposed in accordance with the recommendations for calibration of the brachytherapy sources in terms of reference air kerma rate and were found to be in good agreement with data available in the literature. Our calculations for 125I sources (models 6702 and 6711), provided that the characteristic x-rays from titanium encapsulation are taken into account, support recent experimental and theoretical dose rate distributions indicating that currently accepted values for 125I may be overestimated.
1. The subcellular distribution of gold in the livers, kidney cortex and the spleens of rhesus monkeys was determined at 2, 10 and 20 days after the administration of sodium (195Au)-aurothiomalate. The serum gold levels were also determined over the period of study. 2. With the continued decrease in the serum gold levels from day 1 to day 20, a continued increase in the tissue levels of the organs studied was observed. The corresponding subcellular fractions of the tissues also showed continued increases in the radioactive concentrations of gold. 3. Gold was found to localise in all the organelles of the cells in the liver, kidney cortex and the spleen, though in varying amounts. The largest increases in the concentrations of gold from day 2 to day 20 were found in the lysosomal bodies of liver and kidney. The concentrations in the kidney cortex increased from approximately five times those in the liver or the spleen on day 2 to about eight times those on day 20.