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On the basis of 77 cases report is given on the treatment of chronic synovitis of the knee in rheumatoid arthritis with radioactive isotopes. Gold 198 and Yttrium90 have been applicated. During an observation period up to 6 years a follow-up on 46 knee joints has been carried out. Very good and good results could be achieved in 50% of these cases.
Veiled cells (VC), isolated from the thoracic duct of irradiated lymphadenectomized mice (MLNX) or peritoneal macrophages (PM phi were incubated with isotope-labelled hen egg lysozyme (HEL), purified protein derivative (PPD) or keyhole limpet haemocyanin (KLH) in vitro. About 2-10 times less antigen was associated with VC than with PM phi when measured in a Philips well-type scintillation counter. Autoradiographs of these cells indicated that 3-10% veiled cells had silver grains associated with them in contrast to 20-95% of the PM phi, depending on the type of antigen studied. It was also shown, from the distribution curves for grains in individual cells, that VC contained smaller numbers of grains than PM phi. Transmission electron microscopy using KLH conjugated with colloidal gold and immunofluorescence microscopy using KLH-FITC confirmed the results obtained from autoradiographs. However, measurements of the uptake of KLH-FITC by individual VC and PM phi using flow cytometry indicated that antigen was associated with nearly all VC in vitro but in much smaller amounts than with PM phi. Both VC and PM phi were capable of presenting HEL to primed T lymphocytes in vitro. These results are discussed in relation to the function of VC as accessory cells compared with PM phi.
Scintigraphic studies made in 75 patients, respectively on 130 testicles with the aid of the organ radio-isotopic lymphography enabled to determine more exactly the location and the variety of the testicular lymph centers. It should be pointed out that in 58.5% of the patients the lymph centers are situated on the left of the middle line and only in 6.1% on the right. In some cases iliac lymph nodes were demonstrable. Attempts were made to use this method in investigation of the patients with malignant tumours of the testicles.
In order to quantitate and to determine the extent of binding of a heavy atom derivative to ribosomal particles and other components of protein biosynthesis, we prepared a 14C-radioactive labeled monofunctional undecagoldcluster. This cluster can be bound either to exposed sulfhydryl groups at the surface of the ribosomes and its subunits, or to high nucleophilic amino groups of nucleic acids as well as to proteins.
Dosimetry theory related to volume sources containing uniformly distributed beta-emitting radionuclides predicts a rapid drop in dose at the outer surface to approximately one half of the maximum dose within the volume. The purpose of this study was to determine if this reduction in surface dose could be observed using a measurable biological endpoint. In this study rats were injected with radiocolloids of either 198Au, 113In-m or 99Tc-m, to produce liver irradiation from their decay, or their livers were treated with external X-irradiation. After irradiation, a portion of the liver was surgically removed to stimulate cell division in the liver remnant revealing radiation damage in the form of chromosomal aberrations. The percentages of dividing cells with bridges were scored in the outer edges (0.45 mm) of the tissue sections and were compared to levels obtained from the central portion of the liver lobe. No significant difference was observed with X-irradiation or from 99Tc-m irradiation. However, irradiation with 198-Au and 113In-m (which emit large numbers of energetic electrons) produced significantly fewer aberrations in the outer layer when compared to the central portion. These differences in the distribution of biological damage allowed us to detect the predicted dose reduction at the surface of volume sources containing beta emitters.
Personal experience of Technetium-99m-sulfur colloid in the scintiscanning of bone marrow is reported. The method offers technical advantages over other methods and superior protection, while its only limitation is that it does not permit a dynamic study of hematopoiesis. Four pathologic scans typical of four groups of diseases may be distinguished. Further, metastatic bone marrow localisations can be diagnosed much earlier and more precisely than by radiography.
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Our experiments aimed at the in vitro development of cells similar to macrophage foam cells of vessel wall. Fatty macrophages were produced by Intralipid incubation of peritoneal macrophages and their motility was studied in vivo. Our results showed that fat-saturated, isotope and colloid-gold marked macrophages can get through the vessel wall, so they are able to in vivo migration.
Double isotope-labelled auro thiomalate (Au195-C14-thiomalate) has been administered to mice and rats, and the excretory fate and tissue distribution have been studied. The results show that the gold and the thiomalate separate in vivo resulting in protein-bound gold and release of free thiomalate. About half of this thiol is excreted in the urine during the first day and the remaining half is taken up by the tissues. Thiomalate penetrates cellular membranes poorly, but is able to interact slowly with proteins (mixed disulphide formation). Part of the thiomalate which remains in the body is membrane bound. In contrast to penicillamine little thiomalate remains in circulation a few hours after administration. Gas chromatography--mass spectrometry has been used to search for the presence of free thiomalate in rheumatoid arthritis patients on Myocrisin (auro thiomalate) therapy. Thiomalate was found in their urine, but not in serum and synovial fluid 20 hours after administration. As thiomalate is released in the body after administration of Myocrisin. the question arises whether this thiol, like penicillamine, may have a beneficial effect in the treatment of rheumatoid arthritis.
The interaction of gold(I) thiomalate (Autm) (Myocrysine) with ergothionine (ErSH) has been studied in aqueous solution at pH 7.4. It was found that ErSH forms a ternary complex of the type ErS-Au-tm at a 1:1 mole ratio; unlike other thiols (e.g., cysteine and glutathione) it does not eject thiomalate (Htm) as a free ligand. However, in the presence of glutathione (GtSH), both ligands, ErSH as well as Htm, from the ErS-Au-tm complex were freed. The 13C NMR chemical shifts of C-2 resonance of ergothionine in the presence of Autm shifts greater than imidazolidine-2-thione (Imt) and 1,3-Diazinane-2-thione (Diaz), indicating the stronger complexation of ErS-Au-tm compared to Imt-Au-tm and Diaz-Au-tm.
The potential hazards from internally administered radionuclides used in nuclear medicine are usually compared with one another and with diagnostic x-rays on the basis of the absorbed dose in rads, with no regard to the dose rate of the radiation. This study compared the carcinogenic potential of a dose of 250 rads delivered at different dose rates to rat livers by x-ray, 113mIn, and 198Au. The chemical carcinogen N-2-fluorenyldiacetamide was administered after irradiation to reduce the latent period and increase the number of radiogenic liver tumors. No significant difference in tumor incidence was observed among groups of animals treated with either 198Au, 113mIn, or x-irradiation.
The distribution of gold in Kupffer cells and in subcellular fractions of rat liver was studied at intervals following intraperitoneal injection of 195Au sodium thiomalate (Myochrysine). Kupffer cells, isolated by digestion of whole liver with Pronase, had radioactive gold counts per milligram of protein that were twice the counts in the digested liver supernatant. After fractionation of liver cells by differential centrifugation, radiogold was found predominantly in the nuclear, mitochondrial, and lysosomal fractions. When the distribution of isotope was related to the protein content, the highest gold concentration was found in the lysosomal fraction, where it was 28 times that in the soluble fraction. Most radiogold was nondialyzable, probably a result of binding to larger intracellular compounds. Approximately 95% of the nondialyzable gold was in the organelle membrane of attached to membrane-adsorbed material, as determined by treatment of dialyzed mitochondrial and lysosomal fractions with Triton X-100. These data suggest that the intracellular locus of gold action may reside in organelle membranes.
Carbon rod atomic absorption analysis (CRA) was applied to the quantiation of gold lymphocyte content (GLC) during chrysotherapy. Sensitivity and accuracy of CRA compared favorably with 195Au isotopic scintillation counting, circumventing the limitations and hazards of the latter in clinical applications. Picogram gold quantification of limited sample volume, less than 10 ml blood, e.g., 10(4)-10(5) lymphocytes (5 microliters) containing 5-10 pg was achieved. GLC after IM administration increased significantly in 60% of patients; for the remainder, GLC was observed to be independent of plasma gold content or cumulative dosage. GLC during auranofin administration (6 mg/day p.o.) approached values for IM gold despite significantly lower plasma levels. Unique sensitivity of CRA enables analysis of GLC under therapeutic conditions that could elucidate whether gold alters functional determinants.
Between 1983 and 1987, 56 patients with choroidal melanoma were treated at the University of Southern California with episcleral plaque (RPT). There were 29 female and 27 male patients, with a mean age of 59 years. Tumor stage at diagnosis was T2 in 18 (32%) and T3 in 38 (68%) patients. The tumor height ranged from 2.9 to 15 mm (mean 6.8 mm). Radial dimensions ranged from 5 to 25 mm (mean 13.2 mm), and circumference ranged from 7 to 23 mm (mean 12.3 mm). Most (77%) patients had posteriorly located tumors, including 18% that were juxtapapillary. Custom-designed gold plaques were utilized in this study. Radioactive isotopes used were 125I for 26 procedures or 192Ir for 31 procedures. A total of 56 patients were treated, with one patient having two procedures. Radiation doses at the tumor apex ranged from 29.8 to 165.4 Gy (mean 94.5 Gy), with the dose at 5-mm depth ranging from 70.5 to 430 Gy (mean 161.5 Gy). Follow-up ranged from 29 to 57 months (mean 39 months). The overall 4-year survival was 96%, with a 91% incidence of free-of-disease progression at 4 years. The majority (84%) of patients experienced a decrease in tumor height, with 27 (48%) patients having greater than 50% decrease. Increase in tumor height was noted in 5 (9%) and no change in 4 (7%) patients. Useful vision (greater than 5/200) was observed in 59% of patients, including 21% who had improved vision. Metastatic tumor occurred in 5 (9%) patients, with a mean time to metastases of 14 months. There was a good correlation between radial tumor dimension and metastatic disease, p less than 0.001. Treatment complications were observed in 34 (61%) patients, with cataract and retinopathy being the most common. Enucleation was performed in 11 (20%) patients, with a mean time to enucleation of 14.5 months. Causative factors for enucleation were treatment complications in 6 and tumor progression in 5 patients. Enucleations were required primarily in patients with tumors greater than 8 mm in height (p = 0.009). Improved RPT techniques with three-dimensional dosimetry are needed to reduce the overall incidence of treatment complications. Adjuvant hyperthermia is being investigated in an attempt to improve tumor control in patients with larger tumors.
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