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Rheumatology Advance Access originally published online on June 27, 2007
Rheumatology 2007 46(10):1531-1537; doi:10.1093/rheumatology/kem155
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

REVIEWS

Radiosynoviorthesis of medium-sized joints with rhenium-186-sulphide colloid: a review of the literature

R. Klett, U. Lange1, H. Haas2, M. Voth3 and J. Pinkert4

Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Giessen, Germany, 1Kerckhoff-Hospital, Department of Rheumatology, Bad Nauheim, 2Hospital association Bonn, Department of Orthopedics and Surgery, Bonn, 3Bayer Schering Pharma, Berlin and 4Schering Deutschland GmbH, Berlin, Germany.

Correspondence to: Rigobert Klett, Department of Nuclear Medicine, University Hospital Giessen and Marburg, Friedrichstraße 25, 35385 Giessen, Germany. E-mail: rigobert.klett{at}radiol.med.uni-giessen.de


   Abstract
Top
 Abstract
Introduction
 Indications and standard...
 Efficacy of treatment with...
 Safety of RSO with...
 Conclusion
 References
 
Hypertrophy and inflammation of the synovium with various underlying pathologies—such as rheumatoid arthritis, osteoarthritis, haemophilia and spondyloarthropathy—can be treated successfully by radiosynoviorthesis (RSO). For medium-sized joints (shoulder, elbow, wrist, hip and ankle), the radionuclide of choice is rhenium-186. We review the evidence for the efficacy of this local, relatively non-invasive therapy and evaluate its benefits and risks. We conclude good evidence of rhenium-186 RSO in rheumatoid arthritis and haemophilic arthropathy. In the remaining pathologies, up to now, the therapeutic efficacy has not been confirmed by today's most stringent criteria for clinical studies. The available data support rhenium-186 RSO as a suitable second-line treatment for patients in whom other therapies (including locally injected corticoids) have failed, as long as proper attention is paid to correct administration—including post-treatment immobilization and the co-administration of corticoids.

KEY WORDS: Radiosynoviorthesis, Rhenium-186, Rheumatoid arthritis, Osteoarthritis, Haemophilia, Spondyloarthropathy


   Introduction
Top
 Abstract
 Introduction
Indications and standard...
 Efficacy of treatment with...
 Safety of RSO with...
 Conclusion
 References
 
Rheumatic conditions are among the most common diseases encountered today, with a prevalence of about 2% in industrialized countries. They can be divided into those that are primarily inflammatory and those that are primarily non-inflammatory. Among the former, rheumatoid arthritis (RA) is the most common, afflicting 1% of the population in the industrialized world [1]. The latter include haemophilic arthropathy, for example. First-line treatment of RA is systemic, i.e. symptomatic treatment with non-steroidal anti-inflammatory drugs (NSAIDs), accompanied by glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) for ‘modification’ of the underlying immuno-inflammatory events and delay of joint destruction (for reviews of anti-rheumatic systemic therapies see [2–4]). Especially, DMARDs are the subject of intensive development activity from pharmaceutical companies [1].

Local treatment, e.g. inflammation control with topical analgesics or glucocorticoids, is likewise often unsatisfactory in the long term and can, moreover, produce severe side effects. The next step is ablation of the diseased, hypertrophied synovium. Surgical resection of the synovium by open synovectomy is no longer generally practised; today, ‘keyhole’ arthroscopic synovectomy is standard [5]. However, this often fails to remove the entire diseased tissue, and effusion then recurs [6, 7]. Alternative methods to destroy the hypertrophied synovial tissue in situ have included the application of chemical agents such as osmic acid and of radioisotopes. The principle is to apply a substance that causes destruction of the diseased tissue and, ideally, allows restoration of the synovial membrane (synovi-orthesis). Such therapy is today considered an appropriate second-line treatment for patients who have failed to respond to other systemic or topical treatments.

Radiosynoviorthesis (RSO) has been in use for several decades, the first report of its clinical use appeared in 1952 [8]. After injection, the radiopharmaceutical is phagocytized by the superficial synovial cells. The radiation halts the inflammatory activity, including the proliferative and destructive processes, resulting in alleviation of the pain and effusion [9, 10].

The choice of the nuclide for RSO is based upon the tissue penetration depth of the emitted radiation and upon the half-life of the radioisotope used. The penetration depth should be equal to the thickness of the synovium in the joint to be treated, balancing the inferior effect of too shallow penetration against the potential hazard of too deep penetration. The half-life should be long enough to allow good distribution within the synovium and adequate exposure, while being short enough to avoid excessive irradiation and significant leakage from the joint. These criteria have led to the current use of three isotopes for RSO in Europe [11]:

  1. Yttrium-90 (90Y; t1/2 2.7 days; therapeutic penetration depth 2.8 mm) for the knee.
  2. Erbium-169 (169Er; t1/2 9.4 days; 0.3 mm) for the fingers and toes.
  3. Rhenium-186 (186Re; t1/2 3.7 days; 1.0 mm) for medium-sized joints: the hip, shoulder, elbow, wrist, ankle and subtalar joint.

A further criterion for successful RSO is the time of retention of the nuclide within the synovial capsule. This should ideally be longer than the decay time of the nuclide. Adequately long retention times are obtained by using colloids of an insoluble derivative, with an appropriate particle size. For rhenium, the sulphide has been found to be the best in this respect and is the only form used.

A meta-analysis by Kresnik et al. [12] reflects extensive clinical experience with RSO. This study contains data on 2190 joints, of which according to our calculation 115 were treated with 186Re sulphide colloid. The authors defined four groups of diseases, in which the use of RSO was assessed as ‘appropriate’, ‘acceptable’, ‘helpful’ or ‘not indicated’. They concluded that, apart from the underlying disease, the pre-existing morphological damage to the joint is decisive for the therapeutic outcome.

A recently published systematic review on radiosynoviorthesis (RSO using Yttrium-90 colloid [13] underlines its clinical value for the knee joint but the benefit for medium-sized joints remains undiscussed.

The purpose of the present review is to survey the current status of RSO with 186Re and to assess its benefit–risk ratio in the light of all available data. Most studies of this treatment—going back nearly three decades—would not have fulfilled today's rigorous criteria for evidence-based clinical research [14]. However, the studies do provide a substantial body of evidence that allows a serious consideration of the efficacy and safety of the treatment.


   Indications and standard activity range for 186Re RSO
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 Abstract
 Introduction
 Indications and standard...
Efficacy of treatment with...
 Safety of RSO with...
 Conclusion
 References
 
The indication for RSO is, fundamentally, inflammatory hypertrophy of the synovium and thus includes RA, seronegative spondyloarthropathy, osteoarthritis (OA), haemophilicarthropathy, calcium pyrophosphate dihydrate arthropathy, undifferentiated arthritis and other inflammatory joint conditions, chronic joint effusions and pigmented villonodular synovitis. A survey between 1991 and 1993 [15] revealed that, at that time, some 71% of RSO procedures were for RA. Today, there is a trend towards increasing use of RSO in other indications such as OA [16, 17].

According to current best practice [18, 19]:

  1. RSO should only be used as second-line treatment, when all methods of conservative therapy have failed, including intra-articular injections of long-acting corticosteroids.
  2. The recommended activity range for RSO with 186Re sulphide colloid is as follows: for the hip, 74–185 MBq; shoulder, 74–185 MBq; elbow, 74–111 MBq; wrist, 37–74 MBq; ankle, 74 MBq; subtalar joint, 37–74 MBq.
  3. When several joints are being treated in a single session, the total activity administered should not exceed 370 MBq.
  4. The administration of glucocorticoids at the same time as RSO is recommended; apart from their short-term add-on therapeutic effect, they promote healing of the injection puncture and thus help to prevent unwanted radiation-induced necrosis.
  5. Absolute contra-indications to any RSO are pregnancy, breast-feeding, local skin infection and ruptured cysts communicating with the treated joint. Relative contra-indications are extensive joint instability with bone destruction, evidence of significant cartilage loss within the joint and, for patients <20 yrs of age, an unfavourable hazard–benefit ratio.


   Efficacy of treatment with [186Re]-rhenium sulphide
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 Abstract
 Introduction
 Indications and standard...
 Efficacy of treatment with...
Safety of RSO with...
 Conclusion
 References
 
Rheumatoid arthritis (RA)
In Tables 1 and 2, we present a summary of the results of prospective and retrospective trials on the use of 186Re RSO in RA with a follow-up examination after at least 6 months. The clinical efficacy found (percentage of patients fulfilling the success criteria) varied from 42 to 92% in the prospective and 61–80% in the retrospective trials; a closer comparison across trials cannot meaningfully be made as different success criteria and different follow-up periods were used.


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  		TABLE 1. Prospective studies on the efficacy of 186Re colloid in treating rheumatoid arthritis

 

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  		TABLE 2. Retrospective studies on the efficacy of 186Re colloid in treating rheumatoid arthritis

 
As mentioned above, most of these studies—going back eight (Table 1) and nearly 30 yrs (Table 2), respectively—do not fulfil rigorous present-day criteria for clinical research. However, these studies, especially those conducted prospectively, do provide substantial evidence in favour of the efficacy of the treatment.

In the most up-to-date and largest of these studies [20], 129 joints in 81 RA patients (78 wrists, 18 elbows, 21 shoulders and 12 ankles) were randomized to receive intra-articular injections of either 186Re (64 MBq) or cortivazol 3.75 mg. Assessment was performed before and 3, 6, 12, 18 and 24 months after treatment, using verbal rating scales and visual analogue scales for pain, joint swelling, joint mobility and radiological stage; a summary of these results is shown in Table 3. 186Re was observed to be statistically superior to cortivazol 18 and 24 months after treatment, while no statistical difference was seen at 3, 6 and 12 months. After 24 months, the difference in favour of 186Re was significant for pain, swelling, mobility, ‘pain and swelling’ and ‘pain or swelling’. A greater relative risk of relapse in corticoid-treated joints was demonstrated, but only from the second year of follow-up. The study concluded that 186Re and cortivazol had similar efficacy up to 12 months after injection, but that thereafter 186Re became more effective.


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  		TABLE 3. Comparative efficacy of 186Re and cortivazol at different times

 
It was also noted that the Steinbrocker radiological stage at inclusion was not a predictive factor of efficacy. 186Re appeared equally effective in terms of long-term (12–24 months) improvement in pain and swelling, whatever the initial radiological stage. However, during the first 6 months, significantly more rapid improvement was noted in stages I–II than in stages III–IV. This is in line with other observations that the earlier stages of disease are more amenable to treatment by RSO [21–24].

Seronegative spondyloarthropathy
The term seronegative spondyloarthropathy covers a number of pathological conditions, for example ankylosing spondylitis, Reiter's syndrome, psoriatic arthropathy and reactive arthritis. In many respects, their therapy resembles the therapy of RA and follows the principles of treatment of rheumatic diseases. Since here too, the underlying pathology is inflammatory alteration of the synovial membrane, the effectiveness of RSO in this group of diseases does not differ essentially from its effectiveness in RA. Therefore, the two conditions are frequently considered and assessed together [17].

Various authors have reported results of RSO with 186Re in patient groups that also included patients with seronegative arthopathy. In these publications, ‘very good’ and ‘good’ results were reported in around 50% of patients. Kampen et al. [25] conducted a retrospective study on 25 patients with inflammatory joint diseases (other than RA) who received RSO. 186Re sulphide colloid had been administered in one subtalar joint, four wrists, six ankles and one shoulder 6 to 18 months earlier. A questionnaire was sent to the patients during follow-up. Radiation synovectomy did not show significant clinical success (‘good’ and ‘very good’ results with respect to joint effusion and restriction of joint movement were obtained in 6/12 joints); however, no aggravation of symptoms was seen in any of the patients. Menkes et al. [26] reported retrospectively the results of RSO with 186Re in 357 wrists (including 28 cases of seronegative spondyloarthropathy). Among these joints, only 16 joints with psoriatic arthropathy were followed during 6 months. The results obtained in these 16 joints were very good or good in half of the cases (50%). Similar results were observed after between 1 and 2 yrs in a small population. Rampon et al. [27] described good and very good results in seven of eight treated joints after 6 months. Thus, the few results available document a good response in this indication.

Osteoarthritis
Osteoarthritis OA develops from degenerative joint disease; the inflammatory alteration of the synovial membrane is the result of articular degeneration, and the clinical symptoms are a combination of those of the degenerative joint disease and of the synovitis. The proportion of RSO treatments performed for OA is a little above 7% and is rising [15–17]. The response to RSO depends on the extent of involvement of degenerative disease and synovitis, and in the two largest studies with 186Re, it was 78% and 69% (Table 4); the other studies were too small to allow appropriate assessment.


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  		TABLE 4. Efficacy of 186Re colloid in treating osteoarthritis

 
Haemarthrosis (haemophilic arthropathy)
Haemophilia is a hereditary blood coagulation disorder that can occur in various forms. Haemorrhagic arthropathy occurs as a result of bleeding into the joint. Recurrent bleeding into a joint causes a gradual destruction of bone and cartilage, which can lead to the development of various joint alterations and eventually to ankylosis. RSO is indicated when a chronic state of synovitis has developed as a result of repeated articular haemorrhages and when haematological therapy has failed [28]. Articular haemorrhages lead, via various mechanisms, to synovitis, which in turn increases the tendency toward further bleeding into the joint. RSO interrupts this progressive vicious circle by inducing fibrosis of the inflamed synovial membrane.

It has been demonstrated in a number of studies that after RSO the frequency of bleeding is reduced. Molho et al. [29] compared the results of RSO with those of osmic acid administered intra-articularly. They treated 107 patients (206 joints) including 48 medium-sized joints to which 186Re was administered. Six months after treatment, 81% of the joints treated with isotopes showed good results, in contrast to only 44% of those treated with osmic acid. This was confirmed up to 4 yrs after treatment in 28 joints followed-up, of which 17/20 joints treated with 186Re showed improvement compared with only 4/8 joints treated with osmic acid. Similar results (up to 88% success) were obtained by Fernandez-Palazzi and Caviglia [30], with a reduction in haemarthrosis in 14–28% of cases and no more haemarthrosis in 30–60%). In an older study, Fernandez-Palazzi et al. [28] described 9 of 10 treated medium-sized joints without recurrence of haemarthrosis after 6 months. Grmek et al. [31] found 64% good and very good results 7 to 12 months after treatment of elbows and ankles.

In their classification referred to above, Kresnik et al. [12] classify the use of RSO for the treatment of haemarthroses encountered in the context of haemophilia as ‘appropriate’: the success rate in their most favourable group was >80%. The authors describe for haemophilia, considered together with von Willebrand's disease, a reduction in articular haemorrhages and in administration of coagulation factors in 91% of the cases. Therefore, this treatment option is to be recommended. If one considers the alternative option of surgery, with the associated disadvantages of prolonged hospitalization and rehabilitation, anaesthesia and prolonged restriction of joint mobility, these results constitute a strong case supporting the usefulness of 186Re in this indication.

186Re-RSO has a place in the treatment of haemophiliac children and young people (i.e. <18 years of age) [28, 31]. Although preventive treatment makes haemarthrosis rare among children, the risks inherent in the alternatives therapies available are no smaller than those of RSO (see subsequent text). In spite of that, the RSO treatment will often be more unacceptable, especially to a child, than surgery or repeated injections of glucocorticoid. Nonetheless, published data on this are scarce, and in view of the (at least theoretical) risk of radiation-induced malignancy the decision to use RSO must be backed up by a detailed individual case assessment and a scrupulous risk–benefit consideration.

Another potentially important application of 186Re-RSO is expected to be in the developing countries. Here, the health-care services often lack the means to detect, and the resources to treat, haemophilia. Consequently, this disorder is less well controlled than in the industrialized countries, and secondary disorders such as haemarthrosis develop more frequently. Especially, in haemarthrosis RSO can also be performed without proved synovitis. Therefore, in this special field no expensive diagnostic procedure like MRI or bone scintigraphy is needed, and joint-bleeding can be prevented with low cost using RSO.

Other indications
These include the following diseases, where RSO offers a way of treating the inflammatory alterations of the synovial membrane when other conventional therapeutic procedures have failed or are inherently inadequate:

  1. Crystal arthropathy with calcium pyrophosphate crystals: only one publication was found [32]. Twelve shoulders treated with 186Re were included among 32 joints in all. RSO was found to be effective; after an average of 3.3 yrs, the treatment, although lacking a definite analgesic effect, frequently led to lasting cessation of the haemarthrosis.
  2. Undifferentiated arthritis (characterized by synovitis, synovial membrane swelling or effusion) and other inflammatory joint diseases (e.g. borreliosis, Behçet's disease): different authors [27, 33] reported results of RSO with 186Re in groups that comprised some patients with the aforementioned indications, reporting good results overall. There is no evidence that these patients responded differently to those treated because of RA.
  3. Chronic articular effusion: this term is encountered especially in the older literature, where there are no exact data that would allow a differentiation of the origin of the effusion [34]. The pathophysiological picture resembles OA when other mechanical causes have been excluded.
  4. Pigmented villonodular synovitis (PVNS) is a rare benign disease of the synovial membrane that is treated primarily by synovectomy. Very limited data are available on 186Re in PVNS [35]: three patients with PVNS of the hip were treated surgically and with 186Re with clinically good results. Kresnik et al. [12] regarded PVNS as ‘appropriate’ for RSO. As above, RSO may usefully follow surgical synovectomy.


   Safety of RSO with [186Re]-rhenium sulphide
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 Abstract
 Introduction
 Indications and standard...
 Efficacy of treatment with...
 Safety of RSO with...
Conclusion
 References
 
As with any nuclide therapy, safety issues with the 186Re sulphide colloid comprise those associated with radioactivity and those caused by the mechanical or surgical procedures involved or the nuclide's chemical vehicle. The effects of radioactivity may be due to direct radiation from the site of application of the radiopharmaceutical, or to leakage of radioactive material from this site and resulting systemic effects. These safety factors are considered in turn.

Radiation from the application site
The ß-radiation, because of its short penetration distance, reaches only structures in the immediate vicinity of the joint cavity, while the 137-keV {gamma}-ray co-emitted by 186Re, and secondarily generated bremsstrahlung can reach more remote organs. In this connection, the radiation dose to the gonads is the main topic. The highest dose results from a RSO of the hip. For a RSO of other joints, the dose to the gonads is clearly smaller because of the greater distance to the gonads and a lower activity injected. For an activity of 150 MBq of 186Re administered to the hip, the maximal {gamma}-radiation dose to the gonads was estimated as 3.5 mSv, with a further <10% due to bremsstrahlung [36].

Leakage from the application site
There are limited clinical data on leakage of colloidal 186Re sulphide out of treated joints, based upon {gamma}-imaging. Gratz et al. [37] conducted whole-body imaging and when the treated joint was immobilized, activity in the lymph nodes was undetectable; without immobilization of the joint, leakage of 40% was observed.

Van der Zant et al. [38] injected 186Re into 54 ankle joints of 40 patients. Glucocorticoids were co-administered and the joints were immobilized for 3 days. Twent-four hours after injection, {gamma}-camera imaging was performed. The mean activity fractions were: for the lymph nodes, 2.4% of the injected activity (range: 0–9.6%); for the liver, 0.8% (0–5.5%); for total leakage, 3.2% (0–9.6%). A limitation of the study was the rather short time between injection and observation. Nevertheless, the data are relevant because of the large number of patients and in view of the fact that all today's recommendations were adhered to: choice of the ankle joint for the 186Re preparation, co-administration of corticoids and immobilization.

The authors compare the risk of 186Re RSO of the ankle with that of other activities and conclude, for example, that the risk of radiation-induced death in this procedure is 1/25 of the risk of a computer-tomographic chest examination.

Estimation of organ exposure to radiation
It is possible to estimate the radiation dose due to leakage, if certain assumptions are made. These are: (i) The fraction of activity leaking out is 10% of the total activity (this is about three times the most reliable value found to date [38]). (ii) All of this radioactivity is taken up by the reticulo-endothelial system (RES). (iii) The locoregional nodes are a transitory station for the activity coming out of the treated joint and thus contain a constant fraction of the leaked-out activity [39]. (iv) The fraction of the activity in the lymph nodes is about 3% of the injected activity [38]. Together, these assumptions lead to an overestimate (some of the activity is counted both in the RES and the lymph nodes). Finally (v), the distribution of colloid particles is taken to correspond to that given for small colloids [40]: liver 70%, red bone marrow 15%, spleen 10%, remaining tissues 5%. On the basis of these assumptions, the radiation exposure due to uptake by the RES was calculated to be 925 µGy/MBq for the liver, 1370 µGy/MBq for the spleen and 102 µSv/MBq for the effective whole body dose [36]. In a RSO with 75-MBq 186Re these values lead to a radiation dose of 69 mGy to the liver, 103 mGy to the spleen and 7.7 mSv to the whole body.

Up to now, only a small number of studies have calculated the radiation dose by measuring the real leakage using whole body scintigraphy or by measuring blood activity. For an injected activity of 75 MBq, the radiation dose to the whole body, the liver, the spleen and lymph nodes was calculated to be between 2 and 53 mGy, 7.5 and 100 mGy, 26 and 203 mGy and 15 and 35 Gy, respectively [37–39, 41]. (The whole body dose of 0.15 mSv, reported by van der Zant et al. [38], could not be considered because of the described calculation method, this value must result from a calculation error.) The dose to the red marrow was only calculated in one study, which reported a dose of 3 mGy [41]. In a RSO of the hip or shoulder with a maximum activity of 185 MBq the doses are about 2.5 times greater.

For assessment of the benefit–risk ratio of RSO with 186Re, these radiation-absorbed doses should be seen in comparison with the radiation doses incurred by other diagnostic and therapeutic medical measures.

The lower value (2 mGy) of the whole body dose range is exceeded by a great number of very frequently performed diagnostic procedures in nuclear medicine and radiology. Some medical measures such as interventional fluoroscopic procedures (25 mSv) and myocardial perfusion scintigraphy with 201TL (26 mSv) reach values similar to the upper range of the estimated doses. In the radionuclide therapy of benign thyroid diseases with 131I, typical effective doses are about 41 to 46 mSv (excluding the dose to the target tissue thyroid). In the case of treatment of thyroid carcinoma with 131I, a typical effective dose is 287 mSv. In view of the fact that RSO with 186Re is—after failure of intra-articular cortisone administration—the last non-surgical option in patients with painful inflammatory joint diseases, doses in the estimated order of magnitude appear acceptable.

Biological dosimetry—chromosome aberrations
Hitherto, data on chromosome aberrations are also few and far between. One study reported the results of only two patients [42] and one of the patients was treated with both 186Re and 90Y at the same time. Therefore, these data are not helpful. Manil et al. [39] reported biological dosimetry results in 24 patients who received 186Re RSO in up to three joints at the same time (maximal injected activity = 210 MBq). The number of dicentrics increased from Day 0 to Day 7. However, a baseline was not measured for all patients and the patients without baselines account for one-third of the incremental dicentrics observed. Because of this, the result of the study is not meaningful.

Vargas and Fernandez-Palazzi [43] assessed chromosomal structural changes (CSCs) in haemophiliacs who did (n = 31) or did not (n = 31) receive 186Re, and in non-haemophilic controls (n = 110). Pre-malignant CSCs were not found in any of these groups. Non-specific CSCs were found 6 months after RSO with 186Re in 1.25% of the metaphases, but were not found another 6 months later. In the group of haemophiliacs who did not receive radioactive treatment, non-specific CSCs were found in 0.79% of metaphases. In the control group, no non-specific CSCs were found.

Fernandez-Palazzi and Caviglia [30] reported results on the safety of RSO with 186Re in haemophilic patients (age range 6–40 yrs; 65% of the patients were <12-yrs-old). They performed chromosomal studies before RSO in 11 patients and after RSO in seven of these. No pre-malignant chromosomal abnormalities were found (markers, segregations, triradiates, dicentrics or others). Non-specific CSCs were observed in 4.7% of the metaphases before RSO and in 11.94% 6 months after RSO. The results confirmed that changes potentially linked to the radiation appeared equally frequently in irradiated and non-irradiated patients, and that the changes due to the radiation disappear with time, never reaching the dangerous level of 2% of structural changes.

Thus, the sparse data currently available suggest that 186Re RSO does not engender dangerous levels of chromosomal aberrations, but well-designed studies using state-of-the-art methodology, as described by Voth et al. [44], are needed to further disclose a substantial radiation exposure to the patient.

Other adverse effects
None of the publications of studies with 186Re cited in this article describe adverse side effects of the RSO. Tebib et al. [20] report that no serious side effects were observed in any patient, with only light and transient local pain and/or swelling occurring in 24% of cases, regardless of the treatment used. Jahangier et al. [45] mention that no short-term adverse effects were seen, and Göbel et al. [46] state that no complications in the form of joint infection, radiation dermatitis or any periarticular soft-tissue damage were encountered. A nationwide survey in Germany with a standardized questionnaire has shown that only very few side effects are associated with RSO (the survey covered all nuclides currently used in RSO) [47].


   Conclusion
Top
 Abstract
 Introduction
 Indications and standard...
 Efficacy of treatment with...
 Safety of RSO with...
 Conclusion
References
 
RSO with a 186Re sulphide colloid offers a local, relatively non-invasive therapeutic method for the treatment of arthritic joint conditions of various origin in medium-sized joints such as the shoulder, elbow, wrist, hip and ankle. RSO can thus, in many cases, restore the patient's ability to lead a fairly normal life. A good evidence for its therapeutic efficacy exists in RA and haemophilic arthropathy (Table 5). Although in the remaining indications the therapeutic efficacy has not been confirmed by today's most stringent criteria for clinical studies (randomized, double-blind, controlled, correct dosing, sufficiently powered, etc.), the accumulated evidence of the numerous trials and surveys conducted to date indicates strongly that the method is effective. The available data support the efficacy of 186Re RSO as a second-line therapy for patients in whom injection of long-acting steroids has failed. The risk–benefit ratio of 186Re RSO, when it is correctly applied, also compares favourably with the alternatives available.


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  		TABLE 5. Level of evidence (AHCPR [52]) of the different indications

 
Practical details regarding the administration of 186Re and the avoidance of unwanted side effects can be found in the current European [18] and German [19] RSO guidelines designed to ensure the routine attainment of the full effectiveness of the method in a safe manner. Adherence to these guidelines—which are similar in all important points—will ensure that this is the case.

Formula

Conflicts of interest. R.K. has received study sponsoring, consultancy fees and speaker's fees from Schering Germany and CIS Bio.M.V. is an employee of Bayer Schering Pharma, the former owner of CIS biointernational (supplier of Re-186 colloid). J.P. is an employee of Schering Germany, a subsidery of Schering AG, the former owner of CIS biointernational (supplier of Re-186 colloid). The other authors have no conflicts of interest to declare.


   References
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 Abstract
 Introduction
 Indications and standard...
 Efficacy of treatment with...
 Safety of RSO with...
 Conclusion
 References
 

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Submitted 12 February 2007; revised version accepted 4 May 2007.
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