A phase I/IIa study on intra-articular injection of holmium-166-chitosan complex for the treatment of knee synovitis of rheumatoid arthritis

Previous animal studies have established that the intra-articular injection of holmium-166-chitosan complex (DW-166HC) causes effective necrosis of the inflamed synovium with litle leakage of radioactivity from the injected joint. Based on these findings, we conducted a phase I/IIa study to examine the biodistribution of DW-166HC and to assess the safety of DW-166HC for the treatment of knee synovitis in patients with rheumatoid arthritis (RA). A total of 16 patients [1 man, 15 women; median age 49 (range 36-65) years] who had RA knee synovitis refractory to disease-modifying anti-rheumatic drug treatments of > 3 months' duration were randomly assigned to three treatment groups with different radiation doses of DW-166HC: 370 MBq (n = 6), 555 MBq (n = 5) and 740 MBq (n = 5). In each treatment group, blood and urine radioactivity were analysed by beta counter and biodistribution of the injected DW-166HC was evaluated using a gamma scan camera. Clinical assessment was done according to three variables (evaluation method): knee joint pain (visual analogue scale), range of motion (goniometry) and joint swelling (circumference of knee joint). The duration of follow-up observation was 3 months. Following the intra-articular injection of DW-166HC, the blood radioactivity was little changed from the baseline measurement and the accumulated radioactivity excreted in urine was minimal. Gamma scan study indicated that most of the injected radiochemical was localized within the injected joint cavity, and the extra-articular leakage was negligible at 24 h after the injection: brain, 0.3%; lung, 0.6%; abdomen, 0.7%; and pelvis, 0.8%. Major adverse events were transient post-injection knee joint pain and swelling. These results suggest that DW-166HC might be a safe agent for radiation synovectomy, particularly for the treatment of knee synovitis of RA, and further trials in a larger patient population are warranted to evaluate the therapeutic efficacy of DW-166HC.     

Experimental radiation synovectomy in rabbit knee with holmium-166 ferric hydroxide macroaggregate

Holmium-166 ferric hydroxide macroaggregate (Ho-166 FHMA) particles possess two important properties for radiosynovectomy; relatively short half-life of the radioisotope and appropriate carrier size. Both these minimize radioactive leakage from the treated joint. This study was conducted to assess the effects of Ho-166 FHMA on synovium and synovial fluid in rabbit knee joints. Whole-knee autoradiography was utilized to determine distribution of radioactivity after intra-articular Ho-166 FHMA injection. Intra-articular injection of Ho-166 FHMA resulted in focal acute radiation necrosis in synovial lining but no hyperplasia of synoviocytes. Later, subsynovial fibrosis became evident. White blood cell and total protein levels in the joint fluid were elevated because of intra-articular inflammation due to the acute effects of radiation. Whole knee autoradiograms showed uneven distribution of the radionuclide along the synovium and extraarticular leakage on the third day after treatment.     

153 Sm-柠檬酸-羟基磷灰石滑膜切除术治疗类风湿关节炎膝关节积液

目的观察^153Sm-柠檬酸-羟基磷灰石（HA）滑膜切除术治疗类风湿关节炎（RA）持续性膝关节积液的疗效和安全性.方法常规抗风湿药物治疗无效的RA患者43例,共67个持续性积液的膝关节,行^153Sm-柠檬酸-HA滑膜切除术,观察其疗效和不良反应.结果注射后24 h 8例患者关节外放射性泄漏占注射总量的百分比均＜1%.随访至治疗后3、6、12、24和36个月,总有效率分别为65.7%、85.1%、77.6%、64.2%和56.7%.随访至36个月时,治疗有效的关节复发率为33.3%.治疗有效的关节表现为肿痛缓解,积液量减少,滑膜厚度减小,关节功能活动改善.不良反应主要为一过性关节肿痛加重.结论^153Sm-柠檬酸-HA滑膜切除术治疗RA持续性膝关节积液短期、中期疗效及安全性较好.     

Biodistribution and excretion of radioactivity after the administration of 166Ho-chitosan complex (DW-166HC) into the prostate of rat

Purpose The objective of this study was to determine the fate of the ¹⁶⁶Ho-chitosan complex (DW-166HC) in rats by examining its absorption, distribution and excretion after administration into the prostate.Methods About 100 Ci of DW-166HC [containing 0.1875 mg of Ho(NO₃)₃·5H₂O and 0.25 mg of chitosan] was administered intraprostatically. The level of radioactivity in blood, urinary and faecal excretion, and radioactivity distribution were examined. To determine the effect of chitosan in DW-166HC, ¹⁶⁶Ho nitrate alone [0.1875 mg of Ho(NO₃)₃·5H₂O] was administered into the prostate of male rats, and radioactivity distribution was examined using whole-body autoradiography.Results After administration of DW-166HC into the prostate, cumulative urinary and faecal excretion over the period 0–72 h was 0.35% and 0.11%, respectively. The radioactivity at the administration site was extremely high at all time points up to 144 h (>98% of injected dose). The small amount of radioactivity which did transfer from the administration site distributed mainly to the liver, spleen, kidney cortex and bone. Compared with the DW-166HC group, the group that received ¹⁶⁶Ho nitrate alone displayed three- to fourfold higher levels of radioactivity in the main tissues, including liver, spleen, kidney cortex and bone, at 24 h after administration (P<0.05).Conclusion The results of this study show clearly that most of the administered DW-166HC remained at the administration site. It is concluded that the chitosan complex may be used to retain ¹⁶⁶Ho within a limited area in cancer of the prostate.     

Radiation synovectomy using 188Re-tin colloid improves knee synovitis as shown by MRI in refractory rheumatoid arthritis

BACKGROUND: Radiation synovectomy is a useful local treatment for patients with refractory synovitis. We previously demonstrated the efficacy and safety of Re-tin colloid for treating rheumatoid arthritis patients with refractory knee synovitis. This open-label, prospective controlled study investigates magnetic resonance imaging (MRI) changes as well as clinical response in knees after receiving different radioactivities of intra-articular Re-tin colloid. METHODS: Sixteen patients with rheumatoid arthritis refractory to intra-articular corticosteroid therapy were treated with intra-articular injection of Re-tin colloid (555 MBq in six patients, 740 MBq in five, and 925 MBq in five). Contralateral knees were used as controls. Treatment efficacy and safety were evaluated 1, 3 and 6 months later. We compared the changes of synovial thickening and joint effusion between baseline and 6 months. Synovial thickness was measured by gadolinium-enhanced MRI. RESULTS: Pain intensities on a visual analogue scale were significantly lower (median pain reduction, 78.9%; P=0.0001), joint swelling improved (median, -1.5; P=0.001), range of motion increased (median, 6 degrees , P=0.005), and joint tenderness decreased (median, -1; P=0.005) in treated knees after 6 months. The control knees did not show any significant clinical improvement. At 6 months after therapy, synovial thickening of treated knees improved in 87.5% of patients (P<0.001), and synovial thicknesses were significantly decreased in treated knees (P=0.0067). Furthermore, reduction in synovial thickness was most noticeable in the group treated with 925 MBq (P=0.007). No abnormalities in leukocyte or platelet counts, liver function tests, or urine analysis were observed. CONCLUSION: Radiation synovectomy using Re-tin colloid in refractory rheumatoid arthritis patients improved MRI findings as well as clinical parameters.     

Effective local control of prostate cancer by intratumoral injection of 166Ho-chitosan complex (DW-166HC) in rats

Purpose The aim of this study was to evaluate the therapeutic effect and morphological alterations resulting from ¹⁶⁶Ho-chitosan complex (DW-166HC) in an animal model of prostate cancer.Methods First, in a subcutaneous tumor model, 80 rats were randomly divided into four groups (n=20 in each group), and intratumoral injections of 0.05 ml (normal saline in group 1, ¹⁶⁵Ho-chitosan complex solution in group 2, DW-166HC solution (10 mCi) in group 3, and DW-166HC solution (20 mCi) in group 4) were performed when the tumor measured approximately 1 cm along its long axis in each group. Further, in an orthotopic tumor model, 40 rats were similarly randomly divided into four groups (n=10 in each group), and intraprostatic injections of 0.05 ml [PBS in group 1, ¹⁶⁵Ho-chitosan complex solution in group 2, DW-166HC solution (0.5 mCi) in group 3 and DW-166HC solution (1 mCi) in group 4] were performed at 1 week after implantation of the AIT cell line in the ventral prostate.Results In the subcutaneous tumor model, mean tumor weights of groups 3 and 4 were significantly lower than those of groups 1 and 2 at 2 and 4 weeks post injection (p<0.05). At 2 and 4 weeks after injection in the orthotopic tumor model, the mean weights of the prostate, including tumor, in groups 3 and 4 were also significantly lower than those in groups 1 and 2 (p<0.05). No adverse injury was seen in adjacent organs at histopathologic examination.Conclusion Intratumoral injection of the beta-emitting radionuclide ¹⁶⁶Ho as a form of complex solution with chitosan appears to be a promising alternative therapeutic modality for the local control of prostate cancer.     

188Re-tin-colloid as a new therapeutic agent for rheumatoid arthritis

Radiation synovectomy is a useful treatment modality in patients with refractory synovitis. We have developed a 188Re-tin-colloid as a new radiopharmaceutical agent and investigated its efficacy and safety in patients with rheumatoid arthritis. Radiation synovectomy was performed using 188Re-tin-colloid in 22 knees from 21 rheumatoid arthritis patients refractory to intra-articular corticosteroid injection. The efficacy and safety of administration of 370-1110 MBq of 188Re-tin-colloid were evaluated after 1, 3, 6, 9 and 12 months. Pain intensity on a visual analogue scale decreased significantly 12 months after therapy (mean+/-SD: 68.0+/-26.1 mm vs. 25.1+/-23.4 mm; P=0.0001 by the paired t-test). Pain decreased in 19 cases (86.3%), joint tenderness improved in 14 cases (63.6%) and joint swelling was reduced in all cases (100%). 188Re-tin-colloid was safe. The residual activity of 188Re in the blood was 0.077%+/-0.25% of the injected dose. The radioactivity of 188Re in the urine was 0.14%+/-0.13% of the injected dose. Transient reactive synovitis was observed in 18 cases (81.8%). No clinical side-effects or abnormalities in leucocyte count, platelet count, liver function tests or urine analysis were observed in any patient. In conclusion, in this first study of radiation synovectomy using 188Re-tin-colloid for patients with rheumatoid arthritis, the treatment resulted in the improvement of arthritis and was well tolerated.     

Bioevaluation of 90Y-labeled particles in animal model of arthritis

Objective  The aim of the present study was to evaluate the behaviour of ⁹⁰Y-labeled particles when injected into an arthritic knee joint of Wistar rats with severe inflammation induced using Complete Freund’s Adjuvant (CFA). Methods   ⁹⁰Y-ferric hydroxide macroaggregates (⁹⁰Y-FHMA), ⁹⁰Y-hydroxyapatite (⁹⁰Y-HA) and ⁹⁰Y-phosphate particles (⁹⁰YPO₄) were prepared, subjected to quality control analyses and in vitro stability studies. Biodistribution studies were carried out by intra-articular injection into knee joints of Wistar rats induced with chronic inflammatory arthritis using CFA and by monitoring the radioactivity for retention and leakage. Results  All the three preparations exhibited ~99% localization in knee joints even at 24 h p.i. with very small amounts observed in the liver and lungs, possibly due to leakage of the radiolabeled particles from the inflamed knee joint. Absence of any radioactivity in the femur indicated the in vivo stability of the particle preparations. Conclusions  The biodistribution patterns were very similar in the normal and arthritic rats and were associated with negligible leakage (up to 24 h) from the knee joint indicating the potential of all the ⁹⁰Y-radiolabeled preparations reported here, for use in radiation synoviorthesis.     

Measurement of synovial inflammation in rheumatoid arthritis with technetium 99m labelled human polyclonal immunoglobulin G

The ability of technetium 99m labelled nonspecific, polyclonal human immunoglobulin G (^99mTc-IgG) scintigraphy to depict and quantify synovial inflammation was studied in patients with rheumatoid arthritis (RA). Eight patients with clinically active synovitis were injected with 350 MBq ^99mTc-IgG, and imaging took place 4 h later. This resulted in excellent images of inflamed synovium. Significant correlations were observed between individual joint uptake on the scan and scores for joint pain (n=316, p<0.001), joint swelling (n = 300, p < 0.001) or the average of pain and swelling (n = 300, p < 0.001). These results suggest that ^99mTc-IgG scintigraphy may provide an objective, non-invasive test to detect and measure synovitis. Offprint requests to: P.A.H.M. van der Lubbe     

Scintigraphic imaging of knee synovitis in osteoarthritis after intra-articular injection of technetium-99m pertechnetate in the unilateral knee

A case of left knee synovitis scintigraphic imaging is presented in a 66-year-old patient with bilateral knee osteoarthritis and a right knee Baker's cyst, who had undergone a 74 MBq (99m)Tc-pertechnetate intra-articular injection in the right knee. The findings in this case were compared with the intravenously injected methylene disphosphonate technetium-99m ((99m)Tc-MDP) scintigraphic findings and could be interpreted as the result of (99m)Tc-pertechenate through blood communication from the right to the left knee. This case implies that (99m)Tc-pertechnetate may be useful in imaging the synovitis in multiple arthroses even up to 60 min after its administration, instead of the 5 min imaging after the injection of (99m)Tc-MDP.     

Radio-synovectomy in chronic synovitis of the knee joint in patients with rheumatoid arthritis

The influence of intra-articular (i.a.) colloidal 198Au (5 mCi) or 90Y-silicate (5 mCi) on synovitis of the knee joint in patients older than 45 years with rheumatoid arthritis (RA), who had been treated since 1970 in our hospital, was investigated. Of the 89 knee joints of 77 patients studied, 65 had no or minimal radiological abnormalities of the knee joint treated (group I), whereas 24 patients had moderate to severe changes (group II). Before and at regular intervals after radio-synovectomy the clinical response was scored using pain, hydrops and warmth as parameters. The results indicated that 1 year after treatment the percentage of knee joints with a favourable response was greater in group I than in group II (58% versus 25%, P = 0.001). This difference was still present 3 years after treatment. Clinical response showed no correlation with initial inflammatory activity as measured by 99mTc-pertechnetate uptake measurements. However, in group I, those patients with an ESR below 60 mm/h, measured just before radio-synovectomy, more often had a favourable response than those with an ESR in excess of 60 mm/h (P = 0.01). No or only slight complications of radio-synovectomy were noted, whereas leakage of radioactivity from the knee joints was minimal. It is concluded that radio-synovectomy is an effective and safe procedure in those patients with rheumatoid synovitis of the knee joint without the presence of significant radiological damage and the absence of active systemic disease.     

Measurement of synovial inflammation in rheumatoid arthritis with technetium 99m labelled human polyclonal immunoglobulin G

The ability of technetium 99m labelled nonspecific, polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to depict and quantify synovial inflammation was studied in patients with rheumatoid arthritis (RA). Eight patients with clinically active synovitis were injected with 350 MBq 99mTc-IgG, and imaging took place 4 h later. This resulted in excellent images of inflamed synovium. Significant correlations were observed between individual joint uptake on the scan and scores for joint pain (n = 316, p less than 0.001), joint swelling (n = 300, p less than 0.001) or the average of pain and swelling (n = 300, p less than 0.001). These results suggest that 99mTc-IgG scintigraphy may provide an objective, non-invasive test to detect and measure synovitis.     

Is corticosteroid coinjection necessary for radiosynoviorthesis of patients with hemophilia?

PURPOSE: Radiation synovectomy is frequently combined with intraarticular corticosteroid injection in the treatment of rheumatoid arthritis to reduce local inflammation and lymphatic clearance of radiocolloid. However, this practice is not universally accepted because corticosteroids have local and systemic toxicity such as osteonecrosis and cartilage damage and whether simultaneous corticosteroid injection together with radiocolloids is necessary in other forms of chronic synovitis like patients with hemophilia remains to be determined. MATERIALS AND METHODS: In this study, we performed radiosynoviorthesis in 14 joints of 12 patients with hemophilia with chronic knee synovitis without corticosteroid coadministration and measured radiocolloid leakage from the joint space. Five mCi Y-90 radiocolloid was injected under local anesthesia and the needle was flushed with additional lidocaine injection instead of corticosteroid. The joint was then manipulated through a full range of extension and flexion to distribute the particles homogeneously throughout the joint space. The joint was then splinted for 48 hours to minimize leakage from the joint space. After the immobilization period, radiocolloid leakage was evaluated using a gamma camera with a 20% window centered over the maximum Bremsstrahlung photopeak of Y-90. Regions of interest were drawn to the injection site on the knee joint and to the ipsilateral inguinal lymph node area. Leakage of radiocolloid was calculated by dividing the background-corrected counts/pixel at the inguinal region by the counts/pixel at the injection site. RESULTS: One of 12 patients who had knee arthroplasty was previously found to have a high amount of leakage. In this patient, 70% of radiocolloid at the injection site drained into the pelvic lymph nodes. In the remaining 11 patients, no lymph nodes were visualized in the groin area and the measured average leakage for these patients was 2.3% (range, 0-13). CONCLUSION: We concluded that in cases of appropriate particle size and strict immobilization of knee joints, leakage of radiocolloid was minimal and steroid coinjection might not be necessary for radiosynoviorthesis of patients with hemophilia with chronic knee synovitis.     

Quantitative 99Tcm-HMPAO white blood cells and 67Ga scanning in rheumatoid arthritis

This investigation assessed 99Tcm-HMPAO white blood cell (Tc-WBC) and 67Ga knee uptake indices before and after 90Y treatment in patients with intractable rheumatoid arthritis (RA) and correlated the uptake indices with the clinical score. Sixteen knee joints with RA were treated with intra-articular injection of 185 MBq of 90Y-silicate colloid (Amersham) flushed with 50 mg of hydrocortisone. Clinical score, quantitative 67Ga and Tc-WBC knee uptake indices were obtained before and three weeks after treatment. Our results showed that 9/16 (56%) had a good response and 7/16 (44%) had a poor response to 90Y injection. There was poor correlation between clinical improvement and changes in 67Ga and Tc-WBC knee uptake indices (r = 0.46 and 0.14, respectively). The correlation coefficient between changes in 67Ga and Tc-WBC knee uptake indices was 0.29.     

Radiation doses from patients undergoing yttrium-90 silicate knee radiosynovectomy

The present study was undertaken because we could not find references related to the minimal radiation doses emitted from patients treated with (90)Y-silicate colloid ((90)Y-SC) for radiosynectomy (RS). Radiation doses from 16 patients treated with about 181+/-13 MBq (90)Y-SC for RS of knee synovitis were estimated by dose rate measurements performed within 10 min after the (90)Y-SC injection with a calibrated survey dose ratemeter at 0.5 m, 1 m and 2 m distances from the treated joint. The mean dose rate values from the patients after bg subtraction were 0.6+/-0.4 microSv/h at 0.5 m, 0.1+/-0.1 microSv/h at 1 m and 0.1 +/- 0.0 microSv/h at 2 m distance. Dose rates at a distance of 0.5 m were significantly correlated (P<0.02) with the patient's weight but not with the height or the injected activity. The assumed estimated maximum whole body doses from a treated patient were 55 microSv for persons living with the patient, 2.9-3.4 microSv for the nursing staff, 0.2-1.8 microSv for the therapist physician and 0.3-0.6 microSv for the technologist, involved in the whole procedure. The above values were lower than those published with the same methodology for alternative RS radiopharmaceuticals for knee synovitis like dysprosium-165 ferric hydroxide macroaggregate ((165)Dy-FHMA) or holmium-166 ((166)Ho-FHMA), as estimated with their typical injected activities. In conclusion our results demonstrate that in (90)Y-SC knee synovectomy, the whole body radiation doses to medical and non medical personnel were as expected well below the maximum annual dose limits for the public and professionals exposed to radiation.     

MR Evaluation of Radiation Synovectomy of the Knee by Means of Intra-articular Injection of Holmium-166-Chitosan Complex in Patients with Rheumatoid Arthritis: Results at 4-month Follow-up

Objective

To determine whether MRI is able to demonstrate the effect of radiation synovectomy after the intra-articular injection of holmium-166-chitosan complex for the treatment of rheumatoid arthritis of the knee.

Materials and Methods

Fourteen patients aged 36-59 years were treated with 10-20 mCi of holmium-166-chitosan complex. A criterion for inclusion in this study was the absence of observable improvement after 3- or more months of treatment of the knee with disease-modifying anti-rheumatic drugs. MR images were acquired both prior to and 4-months after treatment. Clinical evaluation included the use of visual analog scales to assess pain, and the circumference of the knee and its range of motion were also determined. MR evaluation included measurement of the volume of synovial enhancement and wall thickness, the amount of joint effusion, and quantifiable scoring of bone erosion, bone edema and lymph nodes.

Results

Visual analog scale readings decreased significantly after radiation synovectomy (p < 0.05). MRI showed that joint effusion decreased significantly (p < 0.05), and that the volume of synovial enhancement tended to decrease, but to an insignificant extent (p = 0.107).

Conclusion

The decreased joint effusion noted at 4-month follow-up resulted from radiation synovectomy of the rheumatoid knee by means of intra-articular injection of holmium-166-chitosan complex.     

Effectiveness of radiosynoviorthesis in the treatment of chronic synovitis of small and middle-sized joints affected by rheumatoid arthritis

Our aim was to describe and evaluate our experience in the treatment of radiosynoviorthesis (RSO) of small and middle-sized joints in patients with rheumatoid arthritis (RA). Eighty six patients with RA enrolled in the study. The criterion for enrolment was destructive process of the joint detected by X-rays and classified as a stage II-III according to Larsen. Seventy-six middle-sized joints were treated each with 74MBq or rhenium-186 sulphate and other 80 small joints with 10-40MBq of erbium-169 citrate each. The effect of treatment was evaluated at 6 and 12 months following the RSO treatment. The obtained values were compared with those of the initial state. The inflammatory and structural changes in activity were assessed according to the results of ultrasound examination, regression of pain, swelling of the joint and the improvement in mobility. The data obtained were statistically processed with the Chi-square test. Our results showed that RSO significantly decreased pain of the affected joints, however the influence upon joint motion was minimal. The best treatment results were observed in shoulders and elbows, while the ankles were the worst to respond to the RSO treatment. The significant (P<0.05) beneficial effect of the RSO treatment on pain and swelling reduction were only transient started on 1 week to 1 month and declined over 12 months. In conclusion, our study showed that RSO is a suitable alternative in the treatment of chronic synovitis, with a low potential of adverse effects. However the beneficial effect on pain and swelling reduction was only transient and declined over 12 months.     

Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study

Intra-arterial administration of beta-emitting particles that become trapped in the vascular bed of a tumour and remain there while delivering high doses, represents a unique approach in the treatment of both primary and metastatic liver tumours. Studies on selective internal radiation therapy of colorectal liver metastases using yttrium-90 glass microspheres have shown encouraging results. This study describes the biodistribution of 40-µm poly lactic acid microspheres loaded with radioactive holmium-166, after intra-arterial administration into the hepatic artery of rats with implanted liver tumours. Radioactivity measurements showed >95% retention of injected activity in the liver and its resident tumour. The average activity detected in other tissues was А.1%ID/g, with incidental exceptions in the lungs and stomach. Very little ¹⁶⁶Ho activity was detected in kidneys (<0.1%ID/g), thereby indicating the stability of the microspheres in vivo. Tumour targeting was very effective, with a mean tumour to liver ratio of 6.1DŽ.9 for rats with tumour (n=15) versus 0.7ǂ.5 for control rats (n=6; P<0.001). These ratios were not significantly affected by the use of adrenaline. Histological analysis showed that five times as many large (>10) and medium-sized (4-9) clusters of microspheres were present within tumour and peritumoural tissue, compared with normal liver. Single microspheres were equally dispersed throughout the tumour, as well as normal liver parenchyma.     

膝创伤后滑膜炎的关节镜治疗

目的 探讨关节镜在膝关节创伤后滑膜炎中的治疗作用。方法 1987年9月-2000年8月共收治36例，以膝关节肿胀为主要临床表现16例，以“机械型”疼痛为主者12例，两者均有8例，术前均经体检及X线检查，其中7例行MRI检查排除其他损伤，常规关节镜检查后行滑膜切除术。结果 局限性滑膜炎24例，弥漫性炎症12例，镜下表现分为渗出型7例，增生型23例，纤维型6例，9例发现其他病变，32例经平均3.7年随访，28例疗效评定为优良（87.5%)，临床表现关节肿胀为主和镜下渗出型及增生型者关节镜治疗效果较好。结论 关节镜手术治疗膝创伤后滑膜炎既可发现可能存在其他病变，又有良好的效果。     

Synovectomy of the knee with 90Y

In 33 patients with chronic arthritis of the knee, 48 knees were treated with an intra-articular injection of 5 mCi yttrium silicate (90Y). There were 27 patients with rheumatoid arthritis (RA) and 6 with osteoarthrosis (OA); the mean follow-up period was 33 months. At clinical investigation after 1 year, no signs of pain or swelling were found in 15 knees. In most cases, pain and swelling improved subjectively, with a mean duration of 11 months; in 20 knees, the improvement lasted more than 22 months. When radiographs showed severe destruction, 90Y treatment was unsuccessful, but an important new finding was that most patients with mild or moderate radiological abnormalities appeared to have a long-lasting improvement. The result did not correlate with erythrocyte sedimentation rate (ESR), haemoglobin or Rose titre at the time of injection or at follow up, suggesting that the result of the treatment is more dependent on local factors than on the disease activity. The results of 90Y treatment in 6 OA knees with persistent swelling were promising regarding swelling, even in patients with moderate radiological abnormalities. The main side-effect was a sometimes painful swelling of the knee, which was always successfully treated with an intraarticular corticosteroid injection. In 90Y-treated knees, the incidence of unstable joints was not significantly higher than in non-treated knees. In conclusion, 90Y synovectomy may be a successful treatment for patients older than 50 years with chronic arthritis of the knee due to RA and probably also OA, even when moderate radiological abnormalities are present.