Radiosynovectomy: Introduction and Overview of the Literature

Fig. 6.1

A female patient, 72 years with rheumatoid arthritis of the hands. Before radiosynovectomy, scintigraphy is performed to clearly localize the inflamed joints. Tc-99m methylene diphosphonate (Tc-99m MDP) bone scintigraphy shows a typical symmetrical increased tracer uptake in both wrists and small finger joints due to synovitis (right image). Also in the distal interphalangeal joints, synovitis can be seen. The localization is not typical for rheumatoid arthritis and is secondary caused by degenerative changes

The main indications for RSO according to the European procedure guidelines for radiosynovectomy and with modifications to the German and Austrian guidelines [4–6] are persisting synovitis after a 4- to 6-month systemic treatment in:

Rheumatoid Arthritis
Seronegative spondyloarthropathy (e.g. reactive or psoriatic arthritis)
Other inflammatory joint diseases, e.g. Lyme disease and Behcet’s disease
Undifferentiated arthritis (where the arthritis is characterized by synovitis, synovial thickening or effusion)
Persistent synovial effusion (e.g. after arthroscopic synovectomy)
Persistent effusion after joint prosthesis
Osteoarthritis (activated osteoarthrosis)
Pigmented villonodular synovitis (PVNS)
Haemophilic arthritis

Contraindications
Pregnancy
Breast-feeding
Local skin infection
Acute rupture of popliteal cyst (Baker’s cyst of the knee)

Relative Contraindications
The radiopharmaceuticals should only be used in children and young patients (<20 years), if the benefit of treatment is likely to outweigh the potential hazards.
Extensive joint instability with bone destruction

6.3 Radiopharmaceuticals

The radionuclides that are injected into the articular cavity are phagocytized by the synovial cells. The irradiation leads to fibrotic and sclerosing changes of the synovial membrane and to an occlusion of the superficial capillaries. The inflammation as well as the proliferative and destructive process is stopped. Clinically, the pain and effusion of the treated joints, as well as the mobility get improved [7, 8].

In RSO β-emitting radionuclides are used.

Essential for the choice of the nuclides is the penetration depth of the emitted irradiation in correspondence to the thickness of the synovium and the nuclide’s half-life. The most often used and approved nuclides for RSO in Europe are:

(Nuclide, half-life, mean/maximum penetration depth in tissue)
- Yttrium-90 citrate (Y-90, 2.7 days, 3.6/11 mm) – used for large joints like the knee joints
- Rhenium-186 sulphide (Re-186, 3.7 days, 1.2/3.7 mm) – used for medium-sized joints such as shoulder, elbow, wrist, hip and ankle
- Erbium-169 citrate (Er-169, 9.4 days, 0.3/1.0 mm) – used for small joints in the fingers and the toes, sterno- and acromioclavicular and temporomandibular

Furthermore, not so widespread used radionuclides for RSO are dysprosium-165 ferric hydroxide, holmium-166 hydroxyapatite and samarium-153 hydroxyapatite [9].

6.4 Radiosynovectomy in Rheumatoid Arthritis (RA)

The effectiveness of radiation synovectomy in rheumatoid arthritis was investigated by several authors.

In a meta- analysis 2,190 treated joints were evaluated [10]. There were 1,880 joints with rheumatoid arthritis and 37 patients with seronegative arthritis including psoriatic arthritis, ankylosing spondylitis and Reiter’s disease. One hundred twenty-one had osteoarthritis. The period of observation was 1 year. The mean improvement rate for rheumatoid arthritis was 66.7 ± 15.4 %. For osteoarthritis the success rate was 56 ± 11 %. The results were dependent on the pre-existing morphological changes according to the American Association’s staging criteria (Steinbrocker). The best results were achieved in patients without morphological changes. However, RSO in patients with changes according to Steinbrocker I was successful in 72.8 ± 12.3 % and in 64 ± 17.3 % in Steinbrocker II. Even in joints staged with Steinbrocker III and IV had a success rate of 52.4 ± 23.6 %.

Based on the clinical outcome after RSO, three groups were defined where RSO was indicated. In case of deformed or unstable joints, there was no clinical response. Therefore, RSO was not indicated (Table 6.1).

Table 6.1

Groups for RSO [10]

Group	Clinical response rate	Disease	Pre-existing morphological changes
A (appropriate)	>80 %	Rheumatoid arthritis Haemarthrosis in haemophilia Haemarthrosis in Willebrand’s disease Villonodular synovitis	No changes
B (acceptable)	60–80 %	Rheumatoid arthritis Seronegative arthritis Osteoarthritis Repeating injection in previous responder	Steinbrocker I, II^a Minimal or moderate
C (helpful)	<60 %	Rheumatoid arthritis Osteoarthritis	Steinbrocker III, IV^a Severe destruction
D (not indicated)	No response	Need for surgical interventions Previous nonresponder Deformed joints Unstable joints

^aClassification according to the American Association’s staging criteria (Steinbrocker)

Most of the treated joints were large joints like knees (64 %). Medium-sized joints like shoulder, elbow, wrist, ankle and small finger joints were presented in 17 and 19 %.

Several studies were performed to determine the clinical response in the different types of joints.

6.4.1 Radiosynovectomy of Large Joints

Kampen et al. [11] reported in a summary of prospective studies in which 796 knee joints were treated using yttrium-90 colloid (Y-90) that the success rate ranged from 50 to 100 %. The overall follow-up duration was 6–36 months.

Several authors also compared yttrium-90 colloid (Y-90) with the intraarticular injection of corticosteroids. It turned out that RSO was effective in 78 and 70 % of RA patients in whom corticosteroids were ineffective [12, 13].

Furthermore, in a double-blind study by Urbanova et al. [14], the authors compared Y-90 in combination with corticosteroids. Corticosteroids alone and the combination with Y-90 colloid showed comparable efficacy in reduction of pain and effusion for a short time. But in the long term (after 12 months), Y-90 colloid was superior. The improvement was seen with the variables of pain, functional disability, joint tenderness and swelling.

Similar results were also found in a 6-year follow-up study by Grant et al. [15] in 21 patients with RA. After 6 years, 75 % of the patients that were treated initially with glucocorticoid (GC) needed other treatments (e.g. surgical synovectomy, knee arthroplasty, Y-90 reinjection) versus 66 % of patients in the RSO group (p > 0.05).

In another study [16] the combination therapy was also investigated in 15 patients with chronic pyrophosphate arthropathy of the knee. They found that all outcome parameters were significantly better for the combination of Y-90 and GC injection with regard to pain, stiffness, effusion, range of movement (p < 0.01) and joint circumference (p < 0.05). Therefore, the combination therapy was favoured in chronic pyrophosphate arthropathy.

It seems that the combination therapy is also the preferred therapy concept in clinical routine because, in a survey of radiation synovectomy in Europe, 60 % of the responders reported that they used corticosteroid co-injection with radiopharmaceuticals. Rheumatoid arthritis was the most prevalent disease in patients treated.

Regarding steroids, triamcinolone hexacetonide was most frequently used due of its relatively long residence time in joints.

It was also suggested that corticosteroids reduces lymph node uptake of radiocolloids [17, 18].

6.4.2 Surgical Synovectomy and Radiosynovectomy

Surgical synovectomy is well established in the local treatment of RA.

However, due to traumatization and insufficient removal of all pathological tissue with minimal arthroscopic synovectomy, the recurrence rate was high and amounted to 30 % in a long-term follow-up [2, 3].

Therefore, several authors reported the usefulness of the combination of arthroscopic subtotal synovectomy and radiosynovectomy.

In a recent study by Akmese et al. [19], the authors compared the combined arthroscopic synovectomy and RSO in the treatment of chronic non-specific synovitis of the knee. They found that the limitation of motion and effusion was significantly regressed. Also pain and synovial membrane thickness were significantly reduced (82 and 54 %). Clinically and radiologically on MRI, there was no recurrence after 3 years.

Similar results were also found from other authors. Kerschbaumer et al. [20] reported about significantly better long-term clinical results (8 years) in 141 knee joints that were treated with the combination therapy than patients that were treated with RSO alone.

Furthermore, in another study by Goetz et al. [21], 32 patients with RA of the knees were successfully treated with the combination therapy and also did not need any surgical re-intervention in 84, 44 and 34 % after 5, 10 and 14 years. Similar results were also found from other authors with better results for the combination therapy in the early stages of rheumatically swollen joints. Therefore, the authors suggested to perform the combined therapy for the treatment of early rheumatoid stages of the ankle joint. Additionally, open synovectomy should be preferred to arthroscopic synovectomy if tenosynovectomy is simultaneously required [22, 23].

Regarding the time of RSO, it was suggested to perform RSO 6 weeks after surgery, because after this time the postoperative edema had diminished and the surgical wound is almost closed to avoid any leakage of the injected radionuclide. Moreover, the postoperative inflammatory changes were at the maximum at this time and the efficacy of the anti-inflammatory effect of the RSO was thus increased [19].

Further studies are needed to establish this favourable therapy concept for the chronic non- specific synovitis in the long-term follow-up.

6.4.3 Radiosynovectomy in Knee Endoprosthesis

Radiosynovectomy was also under investigation for treating recurrent joint effusions after knee endoprosthesis.

First results about the usefulness of RSO in knee endoprosthesis were reported by Mödder et al. [24]. In their study 107 patients with chronic joint effusion due to “polyethylene disease” were treated with Y-90. In 93/107 (87 %) patients, joint effusion completely diminished after therapy.

In a recent study by Mayer-Wagner et al. [25], 55 patients with chronic joint effusion after endoprosthetic knee replacement were treated with Y-90 colloid. Significant improvement in pain, effusion and function was seen in 54 %. Most of the patients in whom RSO treatment failed, complications like infection, loosening, allergy and trauma were detected.

In summary, RSO represents a valid therapeutic option in persistent effusion after joint prosthesis. However, in case of treatment failure, endoprosthetic complications should be excluded.

6.4.4 Radiosynovectomy of Medium- and Small-Sized Joints

Rhenium-186 is used for the hip, shoulder, elbow, wrist, ankle and subtalar joint and erbium-169 for finger and toe joints, acromio-/sternoclavicular joints and temporomandibular joints.

It was reported that the efficacy of RSO for medium-sized joints in RA varies from 60 to 90 % (Fig. 6.2a, b).

Fig. 6.2

(a) Arthrogram of the ankle joint during the RSO. The puncture needle can be seen on the left side. (b) Patient with rheumatoid arthritis was submitted for RSO of the right ankle joint. After the injection of 74 MBq rhenium-186, single-photon emission computed tomography (SPECT) is showing the distribution within the ankle joint (arrow)

In two prospective studies by Göbel et al. [26, 27], the authors evaluated the efficacy of rhenium-186 for medium-sized joints (n = 50) and erbium-169 for digital joints (n = 131) in patients with RA. The injection of rhenium-186 and erbium-169 was combined with triamcinolonhexacetonid. The synovitis in the control groups was treated by the injection of cortisone alone. Follow-up time was 3 years. Pain, synovial swelling, joint motion and stage of radiological destruction (based on the staging by Larsen-Dale-Eek) were assessed.

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