Cutaneous radiation necrosis as a complication of yttrium-90 synovectomy

Radiation synovectomy is an effective method of treatment of chronic synovitis in patients with conditions such as rheumatoid arthritis, haemophilic synovitis and pigmented villonodular synovitis. This case demonstrates one of the potential complications of this procedure in a 46 year old man treated with bilateral radiation synovectomy for haemophilic synovitis. Cutaneous radiation necrosis is a known but rare complication of this procedure and this case is reported to demonstrate this known complication and to highlight that appropriate technique is required to avoid this.     

Long-term results of radiation synovectomy: a clinical follow-up study

Radiation synovectomy by intra-articular injection of beta-emitting radionuclides is a reliable and easy-to-perform therapy without harmful side effects for the treatment of inflammatory rheumatoid as well as degenerative joint diseases. The indication for radiation synovectomy is based on both clinical symptoms and on proven hyperperfusion, with active synovitis being seen on a pre-therapeutic three-phase bone scan. In this study, the clinical response after 6-18 months, evaluated by a standardized questionnaire, was compared with the reduction of synovitis seen on three-phase bone scintigraphy after treatment of 475 joints in 151 patients. The best clinical results were obtained in cases of true rheumatoid arthritis (73.4%), with less in other kinds of arthritis (48.8%) such as psoriatic or reactive arthritis. Because of the inflamed synovium being the main target tissue, clinical results in osteoarthritis with severe bone destruction are poorer (33.9%). However, synovitis can be markedly reduced (in approximately 70%), regardless of the underlying diagnosis, as shown by post-therapeutic three-phase bone scanning. Radiation synovectomy can be recommended in all kinds of arthritis. It should also be considered in cases of osteoarthritis as a last therapeutic option prior to joint replacement.     

Radiation synovectomy using 165Dy ferric-hydroxide and oxidative DNA damage in patients with different types of arthritis.

Radiation synovectomy is an effective treatment for chronic synovitis refractory to pharmacological treatment in patients with rheumatoid or seronegative arthritis. Concerns persist about possible radiation-induced cytogenetic damage after radiation synovectomy leading to recommendations to use this technique only in the elderly. Micronucleus (MN) frequency in lymphocytes and urinary excretion of 8-hydroxy-2'-deoxyguanosine (8OHdG) as an indicator of cellular oxidative DNA base damage are biomarkers of radiation-induced cytogenetic damage. The course of both biomarkers was studied in patients with different types of chronic synovitis undergoing radiation synovectomy with very short-lived 165Dy-ferric-hydroxide (DFH). METHODS: Radiation synovectomy of the knee was performed in 13 men and 12 women (mean age, 44+/-15 y) using a mean activity of 9.48+/-1.65 GBq 165Dy-DFH in 27 consecutive treatments. MN frequency in lymphocytes and urinary excretion of 8OHdG, measured by high-performance liquid chromatography, were assessed before and 4 (MN only) and 20 h after radiation synovectomy. RESULTS: Urinary excretion of 8OHdG in patients (in micromol/mol creatinine; pretreatment mean, 3.1+/-3.4; median, 2.27) was not significantly different from that in healthy volunteers (mean, 2.0+/-1.2; median, 1.87) and not altered by radiation synovectomy (post-treatment mean, 2.5+/-1.5; median, 2.04, NS). An increase in 8OHdG levels after radiation synovectomy of more than 1 SD was found in only 1 patient, who experienced leakage to the lymph nodes but who already had elevated urinary 8OHdG levels before treatment. The frequency of MN/500 binucleated cells (BNCs) was slightly lower in patients (pretreatment mean, 4.3+/-2.6; median, 4.25) than in healthy volunteers (mean, 5.4+/-2.3; median, 5.3) and did not significantly change after therapy, either (4-h post-treatment mean, 3.9+/-2.1, median, 3.8; 20-h post-treatment mean, 4.1+/-2, median 3.8 MN/500 BNC). In 22 of 27 treatments, no leakage to nontarget organs could be monitored, whereas leakage to the local lymph nodes and the liver was detected after 5 treatments. CONCLUSION: Radiation synovectomy using 165Dy-DFH causes no significant radiation burden to most patients as indicated by the absence of adverse changes in levels of biomarkers of cytogenetic damage and a low incidence of leakage. These data suggest that the risk of malignancy may not be elevated.     

Clinical efficacy of radiation synovectomy in digital joint osteoarthritis

Purpose Radiation synovectomy was developed for local treatment of rheumatoid arthritis. In this study, the long-term efficacy of radiation synovectomy was retrospectively evaluated in patients with osteoarthritis (activated arthrosis) of the digital joints using an algofunctional score.Methods Fifty-three digital joints in 29 patients (mean age 64.8 years) were treated by intra-articular injection of ¹⁶⁹Er citrate. All joints were painful despite pharmacotherapy and showed an elevated blood pool pattern in a pretherapeutic three-phase bone scan, indicative for local synovitis. The patients were asked to classify their complaints with respect to different daily manual activities on a ten-step pain scale from 1 (total disability) to 10 (lack of any impairment) prior to and after treatment, with a mean follow-up of 41 months. Local signs of osteoarthritis such as joint swelling or pain were additionally evaluated and were scored from progression of complaints to excellent improvement based on patient self-evaluation.Results All patients reported a pronounced improvement in their manual activities. The mean total score of 4.73±0.58 for all activities prior to treatment increased significantly to 6.79±0.47 after radiation synovectomy (p<0.05). The best results were obtained in the thumb base joints, whereas distal interphalangeal joints were frequently resistant to therapy.Conclusion Radiation synovectomy is highly effective in digital joint osteoarthritis with concomitant local synovitis.     

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.     

Rhenium-188 sulphur colloid as a radiation synovectomy agent

Radiation synovectomy has been shown to be an effective treatment for the rheumatoid arthritic knee. In this study, we evaluated the suitability of rhenium-188 as a radiation synovectomy agent. In addition, we were successful in labelling sulphur colloid with¹⁸⁸Re. In vitro stability tests revealed that more than 95% of the¹⁸⁸Re remained in colloid form over a 3-day period. Intra-articular injection of¹⁸⁸Re sulphur colloid into arthritic rabbit joints was followed by gamma camera imaging to quantify the leakage. The mean retention percentages of¹⁸⁸Re colloid in arthritic knees were 93.7% (±1.4%), 90.8% (±1.7%) and 87.2% (±0.6%) at 1 h, 1 day and 2 days, respectively. A biodistribution study of the arthritic rabbits revealed that the highest activity outside the knees was in the liver and the kidneys. Our preliminary results indicate that 188Re sulphur colloid may be an effective radiopharmaceutical for radiation synovectomy.     

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.     

Synovectomy in rheumatoid arthritis of the knee, radiologic investigations (author's transl)]

Pathologic and radiologic investigations of rheumatoid arthritis are compared with regard to their development. Radiologic demonstration of several cases prior to and following synovectomy shows improvement as well as exacerbation of the disease. An increasing mineral content signifies an improvement of the bone lesion. The mineral content depends on reduction of inflammatory activity, increasing motility, and postoperative discontinuation of cortisone therapy. In some cases various lesions at the border line between bone and cartilage as blurring, notching and destructions are disappearing. Reduction of cartilage accompanied with narrowing of the joint spaces will subside postoperatively, too. We have to suppose a regeneration of cartilage under increasing physical strain by functional stimulation. Following synovectomy the structure of subcartilage spongiosa becomes more organized as a sign of regression of inflammatory activity, improved motility and load capacity. Following synovectomy, exacerbation of radiologic symptoms occur mainly in advanced stages of rheumatoid arthritis. We may often see progression of secondary osteoarthritis existing preoperatively in contrast to clinical recovery. The increasing load capacity may cause an identation of the articular surface in cases of extreme osteoporosis. This might result in a false position. These lesions might necessitate further surgical treatment as possibly total joint prosthesis. Following synovectomy in rheumatoid arthritis of the knee, dissolving radiologic symptoms in addition to improvement of the clinical picture may be observed. The poor results of synovectomy in advanced rheumatoid arthritis favours the of early synovectomy during the proliferative and destructive stage of the disease.     

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.     

Histologic study of effects of radiation synovectomy with Rhenium-188 microsphere

Rhenium-188 microsphere is a relatively new radiation synovectomy agent developed for the treatment of rheumatoid arthritis. It has been shown that the levels of unwanted extra-articular radiation are negligible with this agent. A histologic study was conducted to assess the effect of radiation synovectomy on synovium and articular cartilage after intra-articular injection of various doses of Re-188 microspheres into the knee joints of rabbits. Intra-articular injection of Re-188 microspheres into rabbit knee joints resulted in mild reactive inflammation and thrombotic occlusion of vessels which subsided rapidly. Sclerosis of subsynovium could be seen 12 weeks after injection. No evidence of damage to articular cartilage was noted. There was no significant difference in the articular pattern after injection of 0.3 or 0.6 mCi Re-188 microspheres. This study suggests that a treatment dose of Re-188 microspheres causes transient inflammation of synovium without any detectable damage to the articular cartilage of knee joint.     

放射性核素在关节炎治疗中的应用

放射性治疗关节炎包括全身放疗和局部治疗。全身放疗由于不良反应较大,现已很少使用。本文重点介绍放射性滑膜切除术治疗关节炎的作用原理、适应证、操作方法,以及不同核素的临床应用、疗效和减少不良反应的方法。     

Comparison of extraarticular leakage values of radiopharmaceuticals used for radionuclide synovectomy

OBJECTIVES: Radionuclide synovectomy is a reliable therapy in patients with chronic synovitis. However, radiation doses delivered to non-target organ systems due to leakage of radioactive material from the articular cavity are an important disadvantage of this procedure. In this study we compared extraarticular leakage values of the 3 commonly used radiopharmaceuticals; 90Y-citrate, 90Y-silicate and 186Re-sulfide colloid. MATERIALS AND METHODS: Thirty-five patients with persistent synovitis were enrolled in the study. Twenty-two hemophilic, 8 rheumatoid arthritis and 5 patients with pigmented villonodular synovitis were studied. 90Y labeled silicate and citrate were used for knee joints and 186Re-sulfide for intermediate sized joints. Radiocolloid leakage values were evaluated using a gamma camera with 20% window centered over the bremsstrahlung photopeak of 90Y and a respective window over the 137 keV photopeak of 186Re. Regions of interest were drawn over the injection site, the regional lymph nodes and the background areas. Leakage of radiocolloid was calculated by dividing the counts/pixel in the regional lymph node area to the counts/pixel in the injection site. RESULTS: No visible leakage was observed. The median leakage values calculated for 90Y-citrate, 90Y-silicate and 186Re-sulfide were found as 1.9%, 2.4% and 2.7%, respectively. The difference between the variability of leakage values was not statistically significant (p > 0.05). CONCLUSION: There was no significant difference in terms of extraarticular leakage between 9Y-citrate, 9Y-silicate and 186Re-sulfide radiocolloids.     

Utility of Tc-99m human polyclonal immunoglobulin G scintigraphy for assessing the efficacy of yttrium-90 silicate therapy in rheumatoid knee synovitis

PURPOSE: The aim of this study was to determine the utility of Tc-99m human polyclonal immunoglobulin G (HIG) scintigraphy for evaluating the efficacy of yttrium-90 (Y-90) silicate therapy in rheumatoid knee synovitis. MATERIALS AND METHODS: Fifteen patients (13 women, 2 men; mean age, 53.5 +/- 8.4 years) with rheumatoid arthritis had radionuclide synovectomy using 185 MBq (5 mCi) Y-90 silicate to evaluate 24 knee joints with chronic persistent synovitis. Radiologic and clinical evaluations and Tc-99m HIG scans were performed in each patient before radionuclide synovectomy. Each patient was reassessed 3, 6, 9, and 12 months after therapy using clinical examination and Tc-99m HIG scintigraphy. RESULTS: In 14 of 24 knee joints (4 Larsen stage I, 10 Larsen stage II) that had excellent or good clinical responses to Y-90 silicate therapy, the Tc-99m HIG index values 3 months after treatment were significantly lower than the pretreatment index values (P < 0.001). In 13 of these 14 joints, these low index values and clinical results remained constant throughout the 1 year of follow-up. One patient (1 of the 14 knee joints) experienced severe pain and swelling as a result of recurrent arthritis at 9 months, and the Tc-99m HIG index value increased at 9 months and remained high 12 months after therapy. In 10 of 24 knee joints (4 Larsen stage II, 6 Larsen stage III) that had a fair or poor clinical response, Tc-99m HIG index values were statistically similar before and after radionuclide therapy. CONCLUSIONS: Quantitative Tc-99m HIG scintigraphy is a valuable method for assessing the efficacy of Y-90 silicate therapy in rheumatoid knee synovitis.     

Radiopharmaceuticals for radiation synovectomy: evaluation of two yttrium-90 particulate agents

Radiation synovectomy, a noninvasive therapeutic alternative to surgical synovectomy, has not gained widespread acceptance in the United States because of the lack of a suitable radiopharmaceutical. Two new radioactive particles, [90Y]Ca oxalate and [90Y]ferric hydroxide macroaggregates (FHMA), were developed in our laboratory and evaluated for size, stability, and joint leakage. More than 90% of the [90Y]Ca oxalate particles were in the optimal size range of 1-10 microns, and the unbound activity in serum and synovial fluid was 3.7% to 5.0%. Following injection in rabbit knees, leakage of [90Y]Ca oxalate was 5 +/- 2%, with localization primarily in the bone and virtually no uptake by the lymph nodes or liver. Yttrium-90 FHMA particles were larger (95% greater than 10 microns), and at least on a microscopic level, appeared to distribute homogeneously over the articular surface. Leakage of [90Y]FHMA was initially less but eventually slightly exceeded that of [90Y]Ca oxalate. Nevertheless, both radiopharmaceuticals can provide a satisfactory therapeutic dose to the knee with less than half the leakage and a marked reduction in absorbed dose to nontarget tissues compared to previously tested agents. Ease of preparation, physical characteristics of the 90Y beta ray, and apparent lack of substantial leakage from the joint make these agents extremely attractive for clinical evaluation in rheumatoid arthritis patients who are unresponsive to medical therapy.     

Influence of radiation synovectomy on articular cartilage, synovial thickness and enhancement as evidenced by MRI in patients with chronic synovitis.

Radiation synovectomy is a safe and effective treatment for chronic synovitis that is refractory to the repetitive, intra-articular application of glucocorticosteroids in patients with rheumatoid or seronegative arthritis. Short-term and long-term effects of radiation synovectomy on articular cartilage, synovial enhancement and thickness were assessed in a prospective, clinical trial by MRI. METHODS: Thirteen patients (mean age 39+/-13 y) were treated with a median activity of 8.4 GBq 165Dy ferric hydroxide, a radionuclide with favorable physical properties and a well-documented clinical safety and efficacy profile. MRI was performed on a 1.5-T MR unit using a circular polarized knee coil. RESULTS: After a mean observation period of 13 mo, a marked reduction in synovial enhancement was observed in 10 patients. The mean reduction in baseline synovial thickness (mean 7.6+/-3.0 mm) was 24% (P = 0.03) at 1 wk and 42% (P = 0.01) about 1 y after treatment, respectively. Clinically, 9 of 13 patients (69%) exhibited persistent response to radiation synovectomy. The local clinical score, as defined by the reduction in pain, pannus, joint effusion and by the increase in the range of motion, improved significantly (P = 0.01), from a median of 7 (range 4-10) to a median of 2 (range 0-9). One year after treatment, changes in the local clinical score were related to the decrease in synovial enhancement in MRI (r = 0.7, P = 0.008, n = 12). There were no persistent adverse effects, nor was there evidence for any severe radiation-induced damage to the articular cartilage. On later follow-up images, the structure of the articular cartilage remained unaltered in all but 3 patients, who had new, superficial erosions most likely attributed to an active disease with persistence of inflammation. CONCLUSION: This study suggests that radiation synovectomy with 165Dy-ferric hydroxide is effective in terms of reducing chronic synovitis without causing detectable harm to the articular cartilage, as shown by MRI.     

Comparison of Tc-99m HIG and three-phase Tc-99m MDP bone scintigraphy for evaluating the efficacy of Yttrium-90 silicate radionuclide synovectomy

PURPOSE: The aim of this study was to compare Tc-99m human immunoglobulin (HIG) and three-phase Tc-99m MDP bone scintigraphy for the assessment of the efficacy of Y-90 silicate therapy in rheumatoid knee synovitis. MATERIALS AND METHODS: Fifteen patients with rheumatoid arthritis and chronic persistent synovitis in 23 knee joints had radionuclide synovectomy with Y-90 silicate. The patients underwent imaging before and 3, 6, 9, and 12 months after therapy using clinical evaluation, Tc-99m HIG scintigraphy, and three-phase Tc-99m MDP bone scintigraphy. RESULTS: In the 13 of 23 knee joints that showed successful clinical results with Y-90 therapy, the Tc-99m HIG index values obtained 3 months after radionuclide synovectomy were significantly lower than the pretreatment index values (P < 0.001). In the same 13 joints, the Tc-99m MDP index values (in the blood-pool and delayed phases) before and 3 months after therapy were statistically similar. Six months after injection, these values were significantly lower in both the blood-pool (P < 0.001) and late (P < 0.05) phases in all 13 joints. In the other 10 of 23 knee joints that did not respond to treatment, the Tc-99m MDP and Tc-99m HIG index values were statistically similar before and after Y-90 therapy. CONCLUSIONS: Based on these findings, Tc-99m HIG scintigraphy appears to be a valuable method that complements clinical assessment of the efficacy of Y-90 silicate therapy in rheumatoid knee synovitis, starting in the early post-treatment period. However, three-phase Tc-99m MDP bone scintigraphy may be valuable in the late postsynovectomy period.     

Dysprosium (165Dy) hydroxide macroaggregates for radiation synovectomy — animal studies

This paper reports the development of a new chemical formulation, Dy-HMA, to utilise the advantages of dysprosium 165 in radiation synovectomy of certain forms of arthritis. Dy-HMA is a sterile suspension of dysprosium hydroxide macroaggregates (approximately 6 mg Dy/ml) in saline with the majority of particles in the 3–5 μm range. The absence of ferric hydroxide and a higher concentration of dysprosium in the formulation offer advantages over dysprosium ferric hydroxide macroaggregates, Dy-165-FHMA. Biodistribution studies in rats and rabbits with Dy-HMA show less leakage than with Dy-FHMA and considerably less leakage than with yttrium silicate colloid. Rabbits treated with intraarticular injections of Dy-HMA equivalent to 10–30 times the typical clinical dose showed no signs of any toxic effects.     

Dysprosium (165Dy) hydroxide macroaggregates for radiation synovectomy--animal studies

This paper reports the development of a new chemical formulation, Dy-HMA, to utilise the advantages of dysprosium 165 in radiation synovectomy of certain forms of arthritis. Dy-HMA is a sterile suspension of dysprosium hydroxide macroaggregates (approximately 6 mg Dy/ml) in saline with the majority of particles in the 3-5 microns range. The absence of ferric hydroxide and a higher concentration of dysprosium in the formulation offer advantages over dysprosium ferric hydroxide macroaggregates, Dy-165-FHMA. Biodistribution studies in rats and rabbits with Dy-HMA show less leakage than with Dy-FHMA and considerably less leakage than with yttrium silicate colloid. Rabbits treated with intra-articular injections of Dy-HMA equivalent to 10-30 times the typical clinical dose showed no signs of any toxic effects.     

A survey of radiation synovectomy in Europe, 1991–1993

The prevalence of radiation synovectomy practice is unknown. As new particulate radiopharmaceuticals offering many potential advantages are being developed, it seems prudent to appraise the extent, frequency and variation in radiation synovectomy practice. We have evaluated radiation synovectomy practice in Europe over the period 1991–1993 by means of a postal questionnaire. More than 2300 European members of the European Association of Nuclear Medicine were questioned about the number of treated patients and joints, disease prevalence in their patients and the use of radio-pharmaceuticals. Overall, 119/490 (24%) of centres replying to the survey practised radiation synovectomy during the 3 years. There were 13 450 different joint injections in 8578 patients. Rheumatoid arthritis was the most prevalent disease in patients treated (71%) and the most frequently treated joints were knee (46%) and finger joints (20%). Eight different radiopharmaceuticals were employed. Yttrium-90 colloids were most frequently and widely (100/119 centres) used, mainly employed for knee synovectomy but were also used to treat most appendicular joints. Erbium-169 colloid was almost exclusively used to treat finger joints (31/33 centres). Corticosteroid was routinely co-injected in 36/60 (60%) centres. Radiation synovectomy was widely practised throughout Europe during 1991–1993. There are variations in practice illustrated by the diversity of treated arthritides and injected joints and by the use and application of different radiopharmaceuticals.     

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 little 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 antirheumatic 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.