Studies with Radioactive Gold

Abstract

The distribution of Au in the body was investigated in 10 patients with rheumatoid arthritis. These included 4 who were responsive to Au, 3 who were resistant, 2 who had developed hypersensitivity reactions, and one who had not previously received Au. Aurothiomalate, containing Au198, was injected intramuscularly as a single dose of 10 mg and its subsequent distribution was followed by means of a scintillation counter. The concentration in blood, synovial fluid, and urine was also determined. The plasma level varied from O.11 to 0.17 mg/100 ml on the 1st day and thereafter fell gradually to a mean value of 0.02 mg/100 ml by the end of the 2nd week. Where radioactive Au was mixed with inactive Au, the plasma levels of the radioactive variety were in the same range, indicating that the blood level was directly proportional to the dosage used. The lowest plasma levels were encountered in 2 patients who were hypersensitive to Au. The slowest fall in the plasma level occurred in 2 patients who had become resistant to Au therapy. There was no relationship between the plasma level and the activity of the disease process. The Au in the plasm appeared to be completely bound to protein mostly to fibrinogen. The red cell concentration of Au varied from 1/4 of the plasma level on the 1st day to a value equal to or greater than the plasma level by the end of the 2nd week. The concentration in the synovial fluid was slightly less than that in the plasma at the end of the 1st week, but became equal to or greater than the plasma level by the end of the 2nd week. Fluid and fibrin clot from a popliteal bursa removed at operation showed a gold concentration of 0.67 mg/100 ml (plasma level 0.01 mg/100 ml). A similar high concentration was found in a biopsy sample of articular cartilage from the same patient. The injected Au was, excreted slowly in the urine, 15% in the 1st week, and 20% by the end of the 2nd week, by which time very small quantities were being passed. Excretion was unrelated to disease activity or response to therapy, but was more rapid in patients with sensitivity reactions. Apart from the site of injection, the highest scanning counts were obtained over the right hypochondrium, but high values were also noted over the left hypochondrium, pectoral regions, and loins. In the limbs, the counts were greatest proximally and diminished as the scanner was moved peripherally. Of the 70 joints scanned, 40 gave counts in sequence with the non-articular zones, 6 gave counts which were lower and 24 counts, which were higher than those expected from their position in the limb. Painful joints gave high counts 2.5 times more often than symptomless joints. This phenomenon was not limited to the period of time immediately following the injection but persisted when the level in the blood had become negligible. It is suggested that Au compounds may have a local action on inflamed tissues by inhibition of the enzymes concerned in the inflammatory process.