Cytogenetic and scanning study of patients receiving intra-articular injections of gold-198 and yttrium-90.

Abstract

An account of the chromosome damage found in the lymphocytes of thirteen patients who had received injections of gold-198 into knee joints was reported in a preliminary communication (Stevenson, Bedford, Hill, and Hill, 1971a). There were great differences in the amount of damage which followed injections of the same amount of activity in these patients. However, the mean level of damage appeared too high to be explained by the assumption either that it occurred as a result of irradiation of lymphocytes in the injected joint, or that the radionuclide was distributed throughout the whole body, for the average radiation dose to the body would only be about 0 5 rad from the gamma radiation per mCi of gold-198. It was suggested that the high level of chromosome damage in lymphocytes relative to the amount of activity injected was most probably due to the movement of gold from the knee along the lymphatics to the inguinal lymph nodes, where enormous numbers of lymphocytes in transit through the nodes would come within the range of the beta emission of the radionuclide.Many patients have been treated with benefit by gold-198 or yttrium-90 intra-articular injections (Ansell, Crook, Mallard, and Bywaters, 1963;Delbarre, Cayla, Menkes, Roucayrol, Ingrand, and Aignan, 1969; Bridgnan, Bruckner, and Bleehen, 1971), and it seemed important to try to assess more accurately the amount of chromosome damage in lymphocytes in order to attempt to elucidate the prognostic significance, if any, to patients from these procedures. For this reason, and because there is very little available information on the cytogenetic effects of parenterally-administered radioactive isotopes in man, it was decided to investigate further cases.Including those reported in the preliminary paper, 48 patients who have had gold-198 injections, and 22 who have had yttrium-90 injections have now been investigated. None of these patients received any external radiotherapy. As the appendices show, blood samples from some patients were not taken until several months or years after the injections. Some were taken both before and at intervals after treatment, and some patients were scanned after injection in order to determine the distribution of the isotopes.The colloidal gold-198 (half life 65 hrs) and yttrium-90 (half life 64 hrs) were obtained from the Radiochemical Centre, Amersham, catalogue numbers GCS1P and YAS3P respectively.The gold preparation is a colloidal suspension of metallic gold stabilized with gelatin and with particle sizes of up to 20 pm. Most of the activity is in the 10-13 pm particles. The yttrium preparation is ionic yttrium bound to a colloidal ion exchange resin with a particle size range from 20 to 50 pum.

Does yttrium radiosynovectomy increase the risk of cancer in patients with rheumatoid arthritis?

“…The concerns are mostly based on observed chromosomal abnormalities in peripheral lymphocytes after radiosynovectomy. [6][7][8][9] However, the latency period before development of a cancer lasts for years in the case of small doses of radiation. Risk of leukaemia is estimated to be greatest 5-10 years after the exposure, whereas the risk of solid tumours increases during the rest of the lifespan.…”

“…Chromosomal abnormalities have been found in peripheral lymphocytes after radiosynovectomy. [6][7][8][9] The clinical significance of these changes remains unknown. To our knowledge, no studies of the incidence of cancer in patients who have received intra-articular yttrium injections have been reported.…”

Chromosome analysis of lymphocytes from radiation workers in tritium-applying industry

“…The correlation observed between dicentrics and the concentration of tritium in the urine samples of workers is almost identical with the correlation of dicentrics and the duration of occupational exposure ( 0X82, `0X001 and 0X81, `0X001, respectively). As the half-life of peripheral blood lymphocytes is estimated to be approximately 3 years [17,34], the accumulation of exchange aberrations in peripheral blood lymphocytes in a dose-related manner would be expected. Since Spruill et al [33] have recently demonstrated that the half-life of lymphocytes carrying lethal chromosome damage is much lower than 3 years, the incidence of dicentrics obtained in the present study is due to the concentration of tritium in urine rather than to the duration of occupational exposure.…”

How radiation-specific is the dicentric assay?

“…Dvoreckij et al, 1971;Brewen et al, 1972;Pjatkin, 1976 , Ž in patients undergoing radiotherapy Tamura et al, 1970;Pyatkin et al, 1972b;Schmid et al, 1974a;Silberstein et al, 1974;Chee and Ilbery, 1975;Watson andGillies, . Ž 1975 or therapy with radionuclides Arbor, 1964;Cantolino et al, 1966;De la Chapelle et al, 1972;Stevenson et al, 1973;Blackwell et al, 1974;Boyd et al, 1974; . Lloyd et al, 1976 .…”