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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

The results of 394 consecutive cases of knee joint radiation synovectomy (radiosynoviorthesis) using 90 Y

The aim of this study was to assess the treatment results of 90Y radiation synovectomy for chronic exudative synovitis of knee joints. The retrospective data consist of 394 consecutive knee radiation synovectomies performed using 6 mCi (222 MBq) of 90Y. The assessment included 3-point custom pain and joint mobility scale, evaluation of joint’s circumference, binary joint’s temperature evaluation, patellar ballottement test, indications for puncture and its volume in applicable cases. 21 cases had to be forfeited due to missing data regarding follow-up. The final analysis of 373 treatment procedures performed in 253 patients yielded following results—at 6 months after treatment, 80.9% of the patients reported at least partial pain relief (including 33.3% with complete pain relief), which increased to 86.7% at one year. The pain intensity decreased over time, however, the outcomes were worse in older patients. The probability of pain recurrence was 15% at 6 months, and 28% at one year. It was highest in post-traumatic synovitis, and lowest in pigmented villonodular synovitis. The circumference of the treated knee joints decreased over the course of follow-up, however, the decrease was significantly lower in older patients. The fraction of patients with full knee joint mobility increased from 34.6 to 40.6% at 6 months and 49.2% at one year. The percentage of patients that required articular puncture decreased from 62.8% at baseline to about 35.6% at 6 months, and 32.8% at one year. Positive patellar ballottement was found in 68.5% before treatment and remained at about 40–50% during the course of follow-up. The increased temperature of the joint was reported in 51.2% at baseline and decreased to 33% at 6 months and 28.3% at one year. (1) Radiation synovectomy is a safe and effective method of treatment in patients with exudative synovitis, however, the pain recurrence rate is significantly higher in post-traumatic exudative synovitis compared to pigmented villonodular, undifferentiated, and rheumatoid arthritis. (2) Our results suggest that older patients have worse treatment results with radiation synovectomy compared to younger patients.     

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.     

Applied radioactivity in radiation synovectomy with [188Re]rhenium sulfide suspension

BACKGROUND: Early experience demonstrated absorbed dose in radiation synovectomy is about 100 Gy. For reaching this dose, the applied radioactivity should be calculated. METHOD: Twenty-nine synovitic models of rabbit were treated by intra-articular injection of [(188)Re]rhenium sulfide and histological changes of synovium and cartilage were examined. The applied radioactivity was calculated by method of absorbed dose factor. In clinical, eleven haemophilic patients with haemarthrosis were performed radiation synovectomy with treated [(188)Re]rhenium sulfide. The synovial thickness was evaluated by MR and its value was used to calculate the applied radioactivity. After radiation synovectomy, all patients were followed up by synovial thickness, regional inflammation, and clinical course including bleeding frequency. RESULTS: In rabbit models, the synovitic membrane can be eliminated by calculated radioactivity as planed without damaging the joint cartilage. In patients study, all patients exhibited significant reductions in synovial thickness and inflammation after radiation synovectomy with the planed radioactivities of [(188)Re]rhenium sulfide. Post-procedure bleeding frequency reduction in excellent and good reached to 63.6% by 18 months. In the cases of joint bleeding, the need for antihaemophilic factor treatment decreased immensely. Most of the recurrent episodes of bleeding were mild, subsiding with local means. CONCLUSION: The applied radioactivity in radiation synovectomy could be calculated according to thickness of inflamed synovium. Further study including comparison therapeutic results from calculated individual activities with results from fixed activities and long-term follow-up is warranted.     

Clinical applications of 188Re-labelled radiopharmaceuticals for radionuclide therapy

188Re is a radionuclide in which there is widespread interest for therapeutic purposes because of its favourable physical characteristics. Moreover, it can be eluted from an on-site installable 188W/188Re generator, which has a useful shelf-life of several months. Most of the clinical experiences gained with 188Re concern the use of 188Re-1,1-hydroxyethylidenediphosphonate (188Re-HEDP) for bone pain palliation in patients suffering prostate cancer. The maximum tolerated activity was 3.3 GBq 188Re-HEDP and if the platelet count exceeded 200 x 10(9) l(-1), the administration of 4.4 GBq appeared safe. Evidence for repeated administrations of 188Re-HEDP rather than single injections was established. In general, pain palliation occurs in 60-92% of patients with only moderate transient toxicity, mainly related to changes in blood counts. Also in haematology, radioimmunotherapy by means of 188Re might play a role by selectively targeting the bone marrow in patients undergoing conditioning prior to haematopoetic stem cell transplantation. The feasibility of such an approach was proven using a Re-labelled monoclonal antibody directed toward the CD66-antigen. More recently, encouraging safety data on locoregional treatment of primary liver tumours using 188Re-labelled lipiodol were reported. The normal organs at greatest risk for toxicity are the normal liver and the lungs. About 50% of the patients reported mild and transient side effects, mainly consisting of low grade fever, right hypochondrial discomfort or aggravation of pre-existing liver impairment. Besides the applications in oncology 188Re-based therapies have also been pioneered for benign condition such as prevention of re-stenosis following angioplasty and for radiosynovectomy in cases of refractory arthritis.     

Radiolabelling of poly(histidine) derivatized biodegradable microspheres with the 188Re tricarbonyl complex [188Re(CO)3(H2O)3]+

OBJECTIVES: Many radiopharmaceuticals have been studied as radiation synovectomy agents. In this study, we developed a new potential agent for radiation synovectomy: poly(lactic acid)-histidine (PLA-his) microspheres radiolabelled with [188Re(CO)3(H2O)3]+. METHODS: The reaction conditions for the chelation of [188Re(CO)3(H2O)3]+ and the radiolabelling of PLA microspheres were optimized and the stabilities for both steps tested in vitro. RESULTS: The chelation efficiency of [188Re(CO)3(H2O)3]+ reached 93.12 +/- 1.82% with >95% radiochemical purity once the colloidal and free 188Re were removed by a small Sep-Pak column (Plus QMA). More than 90% of radioactivity stayed in the [188Re(CO)3(H2O)3]+ form over 5 h. The radiolabelling efficiency of PLA-his microspheres with [188Re(CO)3(H2O)3]+ was above 92%. After 3 days incubation at 37 degrees C in calf serum, more than 80% of the radioactivity was still bound to the microspheres. CONCLUSION: Such microspheres are potentially useful as a radiation synovectomy agent for the treatment of chronically inflamed arthritic joints. Furthermore, they might be valuable in cancer brachytherapy.     

Radioimmunotherapy for the intensification of conditioning before stem cell transplantation: differences in dosimetry and biokinetics of 188Re- and 99mTc-labeled anti-NCA-95 MAbs.

A new concept is the intensification of preparative regimens for patients with advanced leukemia using monoclonal antibodies (MAbs) with an affinity for beta emitter-labeled bone marrow. 188Re is a high-energy beta emitter that has therapeutic promise. Our first aim was to clarify whether the therapeutic application of 188Re-MAb against nonspecific cross-reacting antigen 95 (NCA-95) can be predicted from biokinetic data derived from 99mTc-labeled NCA-95. Our second aim was to show that a radiation absorbed dose of > or =12 Gy in the bone marrow can be achieved using 188Re-MAb. METHODS: Dosimetric data were obtained for both radiotracers from multiple planar whole-body scans (double-head gamma camera), blood samples, and urine measurements from 12 patients with advanced leukemia. Radiation absorbed doses were calculated using MIRDOSE 3 software. RESULTS: Radiation absorbed doses to bone marrow, liver, spleen, lung, and kidney were 2.24, 0.50, 1.93, 0.05, and 0.90 mGy/MBq, respectively, using 99mTc-MAb and 1.45, 0.43, 1.32, 0.07, and 0.71 mGy/MBq, respectively, using 188Re-MAb. These differences were statistically significant for bone marrow, spleen, and kidney. The main differences were less accumulation of 188Re-MAb in bone marrow (31%+/-13% compared with 52%+/-13%) and faster elimination through urine (25%+/-3% compared with 15%+/-5% after 24 h). On the basis of these data, a mean marrow dose of 14+/-7 Gy was achieved in 12 patients suffering from leukemia after application of approximately 10+/-2 GBq 188Re-MAb. CONCLUSION: Myeloablative radiation absorbed doses can easily be achieved using 188Re-MAb. 99mTc- and 188Re-MAb showed similar whole-body distributions. However, direct prediction of radiation absorbed doses from the 99mTc-MAb, assuming identical biokinetic behavior, is not valid for the 188Re-MAb in a single patient. Therefore, individual dosimetry using 188Re-MAb is needed to calculate therapeutic activity.     

Concentric joint space narrowing of the hip associated with hemosiderotic synovitis (HS) including pigmented villonodular synovitis (PVNS)

Concentric joint space narrowing of the hip is an expected radiographic finding in cases of inflammatory arthritis such as rheumatoid arthritis or sepsis. However, similar joint space narrowing is associated with chronic hemorrhagic conditions that produce hemosiderotic synovitis. Hemosiderotic synovitis results from chronic intraarticular bleeding such as occurs in pigmented villonodular synovitis, generalized bleeding diathesis, synovial hemangioma, and chronic trauma. Five hips in five patients with concentric joint space narrowing not associated with inflammatory arthritis or with hemophilia were reviewed clinically, radiographically, and pathologically. All patients had a hemosiderotic synovitis. The definitive diagnosis of pigmented villonodular synovitis was made pathologically in two cases that demonstrated nodular areas of giant cell proliferation, collagen production, and lipid-laden histiocytes on histologic samples.     

Radiation synovectomy revisited

Radiation synovectomy is a potential weapon in the therapeutic armamentarium of nuclear medicine. It is an attractive alternative to surgical or chemical synovectomy for the treatment of rheumatoid arthritis. In this article the clinical results obtained with radiation synovectomy from the 1950s through 1992 are summarized and reviewed. Even after taking into account the paucity of well-controlled trials and rigorous clinical follow-up, it is clear that radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis. However, the procedure is not widely used because of concerns about leakage of radioactivity from the treated joint, and the resulting high doses that can be delivered to nontarget organs. New approaches to the preparation of radiolabeled particles for use in radiation synovectomy promise to minimize this leakage and thus allow the full potential of this important radiotherapy to be realized. Correspondence to: K.F. Deutsch     

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.     

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.