Eanm procedure guidelines for radiosynovectomy
EANM PROCEDURE GUIDELINES FOR RADIOSYNOVECTOMY
The purpose of this guideline is to assist nuclear medicine practitioners in
evaluating patients who might be candidates for intra articular
treatment using colloidal preparations of 90Y, 186 Re or 169Er
providing information for performing these treatments.
understanding and evaluating the sequelae of therapy.
BACKGROUND INFORMATION AND DEFINITIONS
Radiation synovectomy/radiosynoviorthesis [RS] in this
context means radionuclide therapy of joint synovitis or
synovial processes by intra-articular injection of 90Y
silicate/citrate OR 186Re sulphide OR 169Er citrate. Synovitis
means inflammation of the specialised connective tissue
lining of a joint cavity (synovium).
emits a beta particle with maximum energy 2.27 MeV,
mean energy 0.935 MeV and average soft tissue range 3.6 mm.
emits a beta particle with maximum energy 1.07 MeV,
mean energy 0.349 MeV,
average soft-tissue range 1.1 mm and a
9% abundant gamma emission with a photopeak of 0.137 MeV.
emits a beta particle with maximum energy 0.34 MeV,
mean energy 0.099 MeV and average soft tissue range 0.3 mm.
Intra-articular injection of 90Y silicate/citrate, 186Re sulphide
and 169Er Citrate is approved in Europe for the treatment of
a range of refractory painful arthropathies. Physicians
responsible for treating patients should have an
understanding of the clinical pathophysiology and
natural history of the disease processes, should be familiar
with other forms of therapy and should be able to liaise
closely with other clinicians involved in managing the
patient. The treating clinician should either see the
jointly with the rheumatologist or orthopaedic surgeon
assuming overall management of the patient’s
condition or be prepared to assume that role. The
treating clinician should be appropriately trained and
in the safe use and administration of 90Y silicate/citrate,
186Re sulphide and 169Er citrate therapy.
Clinicians involved in unsealed source therapy must be
knowledgeable about, and compliant with, all applicable
national and local legislation and regulations.
The facility in which treatment is administered must have
appropriate personnel, radiation safety equipment,
procedures available for waste handling and disposal,
handling of contamination, monitoring personnel for
accidental contamination and controlling contamination
90Y silicate/citrate, 186Re sulphide and 169Er citrate are indicated
for the treatment of joint pain arising from arthropathies
• spondylarthropathy (e.g. reactive or psoriatic arthritis)
• other inflammatory joint diseases e.g. Lyme disease,
• calcium pyrophosphate dihydrate (CPPD) arthritis
• pigmented villonodular synovitis (PVNS)
• persistent effusion after joint prosthesis
• undifferentiated arthritis (where the arthritis is
characterised by synovitis, synovial thickening oreffusion
• Pregnancy• Breastfeeding• Local skin infection• Ruptured popliteal cyst [knee]
• The radioparmaceuticals 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
• evidence of significant cartilage loss within the joint
The facilities required will depend on National legislation for the
administration of pure beta emitting therapy agents. If in-
patient treatment is required by National legislation, this should
take place in an approved facility with appropriately shielded
rooms and en-suite bathroom facilities. The administration of 90Y
silicate/citrate, 186Re sulphide and 169Er citrate should be
undertaken in a dedicated room, equipped for sterile injection
procedures, by appropriately trained medical staff with
supporting scientific and nursing staff.
1. Patients considered for intra articular 90Y silicate/citrate, 186Re
sulphide or 169Er citrate therapy will have failed at least one
intra-articular injection of long-acting glucocorticoid (e.g.
methylprednisolone acetate or triamcinolone). Pain will
usually be severe enough to limit normal activities and/or
2. Radiographs of the joints to be treated should be obtained
and reviewed prior to undertaking RS. Weight-bearing views
of lower limb joints should be requested specifically.
Symptoms attributable largely or exclusively to cartilage
damage are unlikely to benefit from RS.
3. Additional imaging procedures may be useful but are not
• Scintigraphic assessment of soft tissues and severity of
active inflammation (e.g. by 3-(2-)phase 99mTc
MDP/HDP/HEDP bone scintigraphy and/or 99mTc-HIG
scintigraphy) of the affected joints.
• Ultrasound - to evaluate synovial structure and
Thickness and exclude ruptured Baker´s cyst.
• Magnetic resonance imaging of the affected joint.
4. Time interval between arthroscopy or joint surgery and
radiosynovectomy should be (2-)6 weeks and between joint
puncture and radiosynovectomy 2 weeks. The minimum
interval between repeated treatments in the same joint is 6
Information for the procedure
Patients should receive both written and verbal information
about the procedure prior to receiving therapy, including the
importance of immobilising the affected joint for up to 48hours
post injection. Informed written consent must be obtained from
1. Patients should be told that 60 - 80 % of patients benefit from
90Y silicate/citrate, 186Re sulphide or 196Er citrate therapy.
2. Patients should be told that response is unlikely within 14 days
of injection and may be delayed until up to one month.
3. Patients should be warned of the risk of a temporary increase
4. Patients should understand that radiopharmaceutical will not
benefit other non-treated joints but some overall positive
effect on other joints may be noticed if steroid is co-injected
5. Patients should be informed of the potential complications of
i. Risks associated with joint puncture – local
haemorrhage; bruising; infection (very rare);
ii. Theoretical risk of exposure to beta emiting radiation
including radiation necrosis (rare) and future
iii. Risk of post injection pyrexia or radiopharmaceutical
1. Joint puncture for radiosynovectomy carries the same risk as
any joint puncture and should follow the rules of strict asepsis.
2. Local skin anaesthesia is advisable.
3. Correct deposition and homogeneous distribution of the
radiopharmaceutical agent in the joint space is essential.
Puncture of all joints other than knee should be performed
under fluoroscopic (X-Ray screening) or ultrasound guidance.
The knee can routinely be injected without imaging
4. If imaging guidance is not used (e.g. knee) then
radiopharmaceuticals should not be injected unless intra-
articular needle placement has been ensured by aspiration of
joint fluid through the needle which is being used to inject the
5. A particle size of at least 5-10 nm is essential to avoid
6. Absolute immobilization of the treated joint(s) for 48 hours
using splints or bed rest is recommended as this will reduce
transport of particles through the lymphatics to the regional
7. Where possible, simultaneous administration of intra articular
long acting glucocorticoids (e.g. methylprednisolone or
triamcinolone) is recommended to reduce the risk/severity of
acute synovitis and to improve treatment response. (e.g.
triamcinolone acetonide 40mg [1ml] for the knee, hip or
shoulder or 20mg [0.5ml] for elbow, ankle, wrist or subtalar
8. The needle through which the radiopharmaceutical has been
injected should be flushed before and during withdrawal with
E Instructions for patients
The importance of joint immobilisation following treatment
should be emphasised. The treating clinician must advise the
patient on reducing unnecessary radiation exposure to family
members and the public. Written instructions should be
Following treatment, patients should avoid pregnancy for at
If inpatient treatment is required, nursing personnel must be
instructed in radiation safety. Any significant medical conditions
should be noted and contingency plans made in case radiation
precautions must be breached for a medical emergency.
Concern about radiation exposure should not interfere with the
prompt appropriate medical treatment of the patient.
Urinary radiopharmaceutical excretion is of particular concern
during the first 2 days post administration. Patients should be
advised to observe rigorous hygiene in order to avoid
contaminating groups at risk using the same toilet facility.
Patients should be warned to avoid soiling underclothing or
areas around toilet bowls for 1 wk post injection and that
significantly soiled clothing should be washed separately. A
double toilet flush is recommended after urination. Patients
should wash their hands after urination.
Incontinent patients should be catheterised prior to
radiopharmaceutical administration. The catheter should
remain in place for 3 to 4 days. Catheter bags should be
emptied frequently. Gloves should be worn by staff caring for
1. 90Y colloids are suitable for the knee joint only. The recommended
activity per joint is 185 – 222 MBq (5 – 6 mCi).
2. 186Re sulphur colloid is suitable for hip, shoulder, elbow, wrist, ankle and
Both the administered activity and the injected volume of 186Re
sulphide colloid vary according to the volume of the joint to be
Adm. activity MBq (mCi)
The total activity of 186Re at a single session should not exceed 370MBq
3. 169Er citrate colloid is suitable for metacarpophalangeal,
metatarsophalangeal and digital interphalangeal joints.
Both the administered activity and the injected volume of 169Er citrate
according to the volume of the joint to be treated as follows:
Adm. activity MBq (mCi)
The total 169Er-citrate activity injected at a single session should notexceed 750 MBq (20 mCi).
Doses of radiocolloids delivered to synovium have been estimated
from models of joints using a series of assumptions. Physicians are
referred to: Johnson and Yanch Arthritis Rheum 1991; 34 (12): 1521-30,
Bowering and Keeling. Br J Radiol 1978; 51: 836-837; Husák et al. Phys
Med Biol 1973; 18 (6): 848–54; Johnson et al. Eur J Nucl Med 1995; 22(9):
Extra-articular (unwanted) radiation exposure and consequent doses
*Significantly greater extra-articular radiation detection in patients within the groupwho did/could not manage to immobilize joints after injection
Guidelines for measuring the activity to be administered
Use a dose calibrator specially configured to quantify beta emissions. Pre and post
administration measurements should be made to establish the exact injected
Post therapy imaging should be undertaken, where possible, to
confirm appropriate radiopharmaceutical distribution within the
Patients should be reviewed 6-8 weeks after injection. Review
should include clinical and laboratory indices of treatment
response, assessment of synovial inflammation and of possible
In cases where clinical evaluation cannot provide reliable
indication of failure/response and where appropriate pre-
injection MR/ultrasound data are available, further
MR/ultrasound may be of value to document changes in
Clinical examination and ultrasound should be repeated at 3-4
months/6 months and 12 months after treatment.
Pain reduction typically occurs 1-3 weeks post injection.
Treatment failure is likely if no response is detected by 6 weeks
A few patients who have failed to respond to the first
radionuclide injection report pain reduction and
improvement of joint function following re-treatment 6 months
later. Two failed injections should not be followed by
ISSUES REQUIRING FURTHER CLARIFICATION
Presumed mechanism of action - After intra-articular
administration the radioactive particles are absorbed by thesuperficial
cells of the synovium. Beta radiation leads to coagulation necrosis and
Many authors recommend combined corticosteriod and
radionuclide administration to reduce local inflammation
and to prolong residence time of the radiopharmaceutical agent in
the joint. The efficacy of combined steroid/radiocolloid therapyshould
be compared with steroid alone in sufficiently powered randomised
There are few well designed trials to evaluate the efficacy of
radiosynovectomy. Only a minority are prospective and most are not well
defined regarding joint disease, stage or sample size.
1. Clunie GPR, Ell PJ (1995) A survey of radiation synovectomy in Europe,
Clunie GPR, Lovegrove FT: Radiation synovectomy. In: Ell and Gambhir
(eds.) Nuclear Medicine in clinical diagnosis and treatment, 3rd edition.
Churchill Livingston Edinburgh Chapter 52.
Farahati J, Reiners Chr, Fischer M, Mödder G et al. (1999) Leitlinie für die
Radiosynoviorthese. Nuklearmedizin 38: 244-245
Göbel D, Gratz S, v. Rothkirch T, Becker W (1997) Radiosynoviorthesis
with rhenium-186 in rheumatoid arthritis: a prospective study of three
treatment regimens. Rheumatol Int 17: 105-108
Heuft-Dorenbusch LLJ, de Vet HCW, van der Linden S (2000) Yttrium
radiosynoviortheses in the treatment of knee arthritis in rheumatoid arthritis:a
systemic review. Ann Rheum Dis 59: 583-586
Johnson LS, Yanch JC, Shortkroff S, Barnes CL et al. (1995) Beta-particle
dosimetry in radiation synovectomy. Eur J Nucl Med 22: 977-988
Jones G (1993) Yttrium synovectomy: a meta-analysis of the literature.
Mödder G (1995) Radiosynoviorthesis: Involvement of nuclear
in rheumatology and orthopaedics. Warlich Meckenheim
9. Savaser AN, Hoffmann K-T, Sörensen H, Banzer DH (1999) Die
Radiosynoviorthese im Behandlungsplan chronisch-entzündlicher
Gelenkerkrankungen. Z Rheumatol 58: 71-78
10. Taylor WJ, Corkill MM, Rajapaske CNA (1997) A retrospective review of
yttrium-90 synovectomy in the treatment of knee arthritis. Brit J Rheumatol36:
11. Weber M (1993) Lokale Gelenkbehandlung bei chronischer Polyarthritis
(cP): intraartikuläre Kortikoide und radioaktive Isotope. Schweiz Rundschau
The European Association of Nuclear Medicine has written and approved
guidelines to promote the cost effective use of high quality nuclear
medicine therapeutic procedures. These generic recommendations cannot
be rigidly applied to all patients in all practice settings. The guidelines
should not be deemed inclusive of all proper procedures or exclusive of
other procedures reasonably directed to obtaining the same results.
Advances in medicine occur at a rapid rate. The date of a guideline should
always be considered in determining its current applicability.
DESCRIPTION OF THE GUIDELINE DEVELOPMENT PROCESS
The EANM Radionuclide Therapy Committee has been involved in the
process of guideline development for undertaking radionuclide therapies
since 1995. A multinational group of therapy experts developed a series of
monographs on the radioncuclide therapy agents licensed for use
throughout Europe. Subsequently a series of protocols was published on the
Internet for use by members of the European Association of Nuclear
Medicine. The monographs and protocols were achieved through a process
of consensus taking note of the evidence available at the time of writing.
The monographs and protocols have been in the public domain for four years
and comments have been received from members of the nuclear medicine
community. The guidelines have been developed using material within the
monographs and protocols and have been formatted to harmonise with the
Society of Nuclear Medicine Therapy Guidelines format.
This guideline has been developed in close collaboration with Dr G Clunie
and Prof M Fischer who jointly contributed to the original text and provided
an invaluable source of practical advice on radiosynovectomy.
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1. The average time it takes for a person to experience pain relief from aspirin is 25 minutes. A new ingredient is added to help speed up relief. Let µ denote the average time to obtain pain relief with the new product. An experiment is conducted to verify if the new product is better. What are the null and alternative hypotheses? (a) H 0 : µ = 25 vs. Ha : µ 25 (GO TO 2) (b) H