Whole-body radiation dose and lymph node irradiation were the first disadvantages reported after radiation synovectomy of the knee joint with Au-198 (11,58). Today, significant whole-body radiation dose and lymph node irradiation can result from extra-articular leakage of the applied radiopharmaceutical by both lymphatic and venous drainage. Leakage rates of up to 48% have been published and a 10% leakage rate is regarded as reasonable assumption in clinical routine. For Y-90, this is mainly because of the lack of strict size control of the colloidal radionuclide. Very small particles leave the joint more easily and can lead to high leakage rates (8). Moreover, colloidal solutions of Y-90 with a pH <6 may contain free Y-90 ions which can easily be transferred from the treated joint (59). After radiation synovectomy with Re-186, the activity in lymph nodes was found to be 6% of the injected activity one week after injection, and 2.1% of the activity was seen in the hepatosplenic area (60). Leakage data on Er-169 colloid report a maximum rate of 14% of the injected activity (61). For Dy-165, leakage rates seem to be comparatively low with no detectable leakage at all in 22 of 27 (62) treated knee joints. In cases of leakage, the mean leakage rate was always lower than 1% of the injected activity resulting in doses to the lymph nodes ranging from 0.5 to 2.4 Gy (63,64) and 0.03 Gy to the liver (65). Low leakage rates are also reported for P-32. Chromic phosphate colloidal particles are about ten times the size of Y-90 colloid particles (66). In 125 joints treated with P-32, leakage rates of less than 2% of the injected activity were found by Siegel et al. in locoregional lymph nodes (38) while Mathew et al. (66) observed no leakage to locoregional lymph nodes, liver, or spleen in 11 pediatric hemophilia patients.
The degree of leakage is influenced by the particle size and radiochemical stability of the radiopharmaceutical and also by the degree of joint movement during the first days after treatment. One single active use of the respective joint was reported to result in a leakage up to 40% of the injected activity (67). Therefore, strict immobilization for at least 48 hours is regarded as mandatory to reduce extra-articular drainage to a minimum. Whole-body radiation-absorbed doses were reported ranging from 9 to 99 mSv after application of 200 MBq of Y-90 into the knee joint with a median of 37 mSv (68). In the same study, the total gonadal dose was 0.1 mSv in women and 0.2 mSv in men. Physical dosimetry using blood sample counts and scintigraphic data showed an effective whole-body dose of 26.7 + 5.1 mSv in radiation synovectomy with 70 MBq of
Re-186 while the effective dose after application of 30 MBq of Er-169 was described to be lower than 1 mSv (60).
Apart from physical dosimetry, biological dosimetry data were obtained in patients after radiation synovectomy. An increase of chromosomal aberrations with a three-fold frequency of dicentric lymphocytes in the regional lymph nodes was described first by Daker in 1979 (69) after treatment of knee joints with Y-90. A French group found an increased rate of chromosomal damages in blood lymphocytes after radiation synovectomy with Y-90 and Re-186 in 11 out of 16 patients for three weeks of follow-up (70). Er-169 failed to induce any chromosomal aberrations, but treatment with Re-186 led to a cumulative increase of dicentric lymphocytes from 5 to 16 out of 10,000 (60). However, other patient studies failed to demonstrate a significant increase of chromosomal aberrations in lymphocytes for P-32 (71) or Dy-165 and Y-90 (72), although some single cases with a raised dicentrics frequency were observed compared with pretreat-ment findings. Furthermore, no adverse changes of biomarkers for cytogenic damage such as the micronucleus frequency in lymphocytes or urinary excretion of hydroxy-deoxy-guanosine were found in patients treated with Dy-165 (62). Based on these findings, some authors do not recommend radiation synovectomy in patients below the age of 40 owing to the possible risk of malignant induction (22,69). However, the long-lasting clinical practice and the lack of any well-documented cases of malignancy resulting from radiation synovectomy suggest a very low and acceptable risk compared with the benefit for the patient (60). The tumor morbidity rate as a result of whole-body irradiation was calculated as 0.4 per 1000 related to International Commission on Radiological Protection (ICRP) 60 risk data (73) and the genetic radiation risk related to United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) data was described to be several orders of magnitude below one per 1000 (74).
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