Radiation Synovectomy Research Articles

Experimental validation of Monte Carlo depth-dose calculations using radiochromic dye film dosimetry for a beta-gamma 153Sm radionuclide applied to the treatment of rheumatoid arthritis.

In this work we compare the Monte Carlo (MCNP4B) calculated beta-gamma depth-dose profile for a liquid 153Sm beta-gamma source used in radiation synovectomy with the experimental depth-dose distribution obtained using radiochromic dye film dosimetry. The calculated and experimental depth-dose distribution shows a very good agreement (within 5%) in the region where the dose deposition is dominated by the beta particle component (first 800 microm depth on tissue-equivalent material). The agreement worsens, reaching a maximum deviation of 15%, at depths close to the maximum range of the beta particles. Finally the agreement improves for the region where the gamma component accounts for one-third of the total absorbed dose (depths >1 mm). The possible contributions to these differences are discussed, as well as their relevance for the application of 153Sm in the treatment of rheumatoid arthritis.

Experimental radiation synovectomy in rabbit knee with holmium-166 ferric hydroxide macroaggregate

Holmium-166 ferric hydroxide macroaggregate (Ho-166 FHMA) particles possess two important properties for radiosynovectomy; relatively short half-life of the radioisotope and appropriate carrier size. Both these minimize radioactive leakage from the treated joint. This study was conducted to assess the effects of Ho-166 FHMA on synovium and synovial fluid in rabbit knee joints. Whole-knee autoradiography was utilized to determine distribution of radioactivity after intra-articular Ho-166 FHMA injection. Intra-articular injection of Ho-166 FHMA resulted in focal acute radiation necrosis in synovial lining but no hyperplasia of synoviocytes. Later, subsynovial fibrosis became evident. White blood cell and total protein levels in the joint fluid were elevated because of intra-articular inflammation due to the acute effects of radiation. Whole knee autoradiograms showed uneven distribution of the radionuclide along the synovium and extraarticular leakage on the third day after treatment.

In vitro and in vivo dissolution behavior of a dysprosium lithium borate glass designed for the radiation synovectomy treatment of rheumatoid arthritis

In vitro and in vivo dissolution behavior of a dysprosium lithium borate glass designed for the radiation synovectomy treatment of rheumatoid arthritis

In vitro and in vivo dissolution behavior of a dysprosium lithium borate glass designed for the radiation synovectomy treatment of rheumatoid arthritis.

Dysprosium lithium borate (DyLB) glass microspheres were investigated for use in the radiation synovectomy treatment of rheumatoid arthritis. In vitro testing focused on weight loss and cation dissolution from glass microspheres immersed in simulated synovial fluid (SSF) at 37 degrees C for up to 64 days. In vivo testing was performed by injecting glass microspheres into the stifle joints of Sprague-Dawley rats and monitoring the biodegradability of the microspheres and the tissue response within the joints. The DyLB microspheres reacted nonuniformly in SSF with the majority of lithium and boron being dissolved, whereas nearly all of the dysprosium (>99.7%) remained in the reacted microspheres. Because the DyLB glasses released negligible amounts of dysprosium while reacting with SSF, they are considered safe for radiation synovectomy from the standpoint of unwanted radiation release from the joint capsule. Furthermore, the DyLB microspheres fragmented, degraded, and reacted with body fluids while in the joints of rats without histologic evidence of joint damage.

Production logistics and radionuclidic purity aspects of 153Sm for radionuclide therapy.

153Sm, an attractive therapeutic radionuclide, was produced by neutron activation of both natural Sm2O3 and 98% enriched 152Sm2O3 targets. The production logistics and radionuclidic purity aspects of 153Sm obtained using both these targets are discussed with respect to the intended end use for metastatic bone pain palliation (MBPP) in terminal cancer patients and radiation synovectomy (RS) of medium size joints. The specific activity of 153Sm obtained was around 11 GBq x mg(-1) (approximately 300 mCi x mg(-1)) and 44 GBq x mg(-1) (approx. 1200 mCi x mg(-1)) from natural and enriched targets, respectively. The level of the long-lived radionuclidic impurity burden in 153Sm obtained from the natural Sm2O3 targets, namely, due to 154Eu (5 Bq x MBq(-1) 153Sm (5 nCi x mCi(-1) 153Sm)) and 155Eu (75 Bq x MBq(-1) 153Sm (75 nCi x mCi(-1) 153Sm)), appears low enough not to pose a problem, both in the palliative treatment of terminal cancer patients (at 1.85-2.22 GBq (50-60 mCi) dose) as well as in RS (at 74 MBq (2 mCi) dose). The 154Eu content in 153Sm from the enriched target was comparable, while, as expected, the level of 155Eu was nearly two orders of magnitude lower. There is a notable overall advantage of 153Sm over the use of 186Re, the other radionuclide of interest for the same purposes.

Recent advances in radionuclide therapy

A variety of radionuclides continue to be investigated and/or clinically used for different therapeutic applications in nuclear medicine. The choice of a particular radionuclide with regard to appropriate emissions, linear energy transfer, and physical half-life is dictated to a large extent by the character of the disease (eg, solid tumor or metastatic disease) and by the carrier used to selectively transport the radionuclide to the desired site. An impressive body of information has appeared in the recent literature that addresses many of these considerations. This article summarizes and discusses the many recent advances and the progress in the clinical applications of therapeutic radionuclides in relatively new and developing areas, such as radioimmunotherapy, peptide therapy, intravascular therapy to prevent restenosis, radiation synovectomy, and bone malignancy therapy. Projections are made as to the future directions and progress in these areas. The crucial issue of a reliable, year-round supply of new and emerging therapeutic radionuclides in quantities sufficient initially for research, and then for routine clinical use, is a very worthy goal which, in the United States, remains to be achieved.

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

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

Preparation of 153Sm-Chitosan Complex for radiation synovectomy

A samarium 153-chitosan complex was prepared by simply mixing acidic solutions of chitosan and 153SmCl 3. When a solution of this complex was injected into the knee joints of rabbits, minimal extra-articular leakage was observed. This can be attributed to the rapid change in the pH of the complex solution from acidic to neutral, resulting in the formation of gel followed by the subsequent retention in the administered site. Thus, the complex solution represents a promising candidate for radiation synovectomy.

Preparation and studies with 90Y-labelled particles for use in radiation synovectomy

90Y-FHMA (Ferric hydroxide macroaggregates) and 90Y-HA (hydroxyapatite) were prepared in >95% yield using 90Y from an in-house 90Sr–90Y generator. Most of the particles ranged from 5 to 20μm in diameter and retained radiochemical purity >95% in human serum for at least 7 days at 37°C. Gamma camera imaging of normal rabbits after intraarticulation of the particles showed complete retention of activity within the knee cavity with no measurable radioactivity leaching out of the joints over a 96 hour period.

General principles and indications of synoviorthesis (medical synovectomy) in haemophilia.

The indication for a synoviorthesis (medical synovectomy) is chronic haemophilic synovitis causing recurrent haemarthroses, unresponsive to haematological treatment. Synoviorthesis is the intra-articular injection of a certain material to diminish the degree of synovial hypertrophy, decreasing the number and frequency of haemarthroses. There are two basic types of synoviorthesis: chemical synoviorthesis and radiation synoviorthesis. On average, the efficacy of the procedure ranges from 76 to 80%, and can be performed at any age. The procedure slows the cartilaginous damage which intra-articular blood tends to produce in the long term. Synoviorthesis can be repeated up to three times with 3-month intervals if radioactive materials are used (Yttrium-90 and Phosphorus-32), or weekly up to 10-15 times if rifampicin (chemical synovectomy) is used. After 30 years of using radiation synovectomy worldwide, no damage has been reported in relation to the radioactive materials. Radiation synovectomy is currently the preferred procedure when radioactive materials are available, however, rifampicin is an effective alternative method if radioactive materials are not available. Several joints can be injected in a single session, although no more than two joints at the same time is probably the best protocol to follow.

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

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

Radiation exposure from patients treated with 165Dy-ferric hydroxide.

In radiation synovectomy about 10 GBq 165Dy-ferric hydroxide is injected into major joints. Measurements of the dose rates were performed at distances of 5 cm, 0.5 m, 1 m and 2 m from the surface of the treated joints (knees) until 200 min after the application in 16 patients in order to estimate the radiation exposure of persons in the neighbourhood of the patients. The highest doses were estimated for the fingers of the technologist (320 microSv) and for the physician (700 microSv). Special shields for the syringes were constructed for dose reduction. The whole-body doses were 103 microSv for the technologist and 40 microSv for the physician. After the discharge of the patient to a ward or home, other persons at 1 m distance from the patient might receive 88 microSv, which is less than 9% of the annual permissible dose. Our results clearly demonstrate that the calculated radiation exposure to personnel and family members is well below the maximum annual dose limit for non-professionally exposed persons.

Prediction of In-Phantom Dose Distribution Using In-Air Neutron Beam Characteristics for Boron Neutron Capture Synovectomy

A monoenergetic neutron beam simulation study was carried out to determine the optimal neutron energy range for treatment of rheumatoid arthritis using radiation synovectomy. The goal of the treatment is the ablation of diseased synovial membranes in joints such as knees and fingers. This study focuses on human knee joints. Two figures of merit are used to measure the neutron beam quality, the ratio of the synovium-absorbed dose to the skin-absorbed dose, and the ratio of the synovium-absorbed dose to the bone-absorbed dose. It was found that (a) thermal neutron beams are optimal for treatment and that (b) similar absorbed dose rates and therapeutic ratios are obtained with monodirectional and isotropic neutron beams. Computation of the dose distribution in a human knee requires the simulation of particle transport from the neutron source to the knee phantom through the moderator. A method was developed to predict the dose distribution in a knee phantom from any neutron and photon beam spectra incident on the knee. This method was revealed to be reasonably accurate and enabled one to reduce the particle transport simulation time by a factor of 10 by modeling the moderator only.

Arthroscopic synovectomy of the knee joint in early cases of rheumatoid arthritis: follow-up results of a multicenter study

A retrospective multicenter study on a total of 93 knee joints in 81 patients with early forms of rheumatoid arthritis treated by arthroscopic synovectomy was carried out. During the average follow-up period of 33 months, the patients' clinical state showed appreciable improvement. The Lysholm score modified by Klein and Jensen increased from 43.2 points preoperatively to 78.1 points at follow-up. Also, the Insall score (knee score and functional score) showed a highly significant increase of 25.7 and 25.2 points to 71.2 and 80.2 points, respectively. Patients receiving additional radiation synovectomy showed a highly significantly better result than those receiving synovectomy alone. Among the individual variables investigated, pain, swelling, and walking distance in particular were improved. Only radiologically was a mild worsening observed (from Larsen stage 1.57 preoperatively to 1.95 at follow-up). The follow-up examination revealed no synovitis in 80.6% of the patients. Subjectively, 76.4% of the patients assessed the results to be good or very good, with only 7.5% remaining unsatisfied. 90.3% of the patients declared themselves in retrospect willing to undergo the operation again.

Preparation of rhenium-188–tin colloid as a radiation synovectomy agent and comparison with rhenium-188–sulfur colloid

As a generator-produced beta-emitting radionuclide, the importance of 188Re for radionuclide therapy is increasing rapidly. We prepared 188Re–tin colloid and compared its properties with 188Re–sulfur colloid. Labeling efficiencies reached >98% for tin colloid at 2 h and 89–94% for sulfur colloid at 3 h. All the preparations were stable for 72 h in water, serum, and synovial fluid. If labeled at higher temperature, the particle size of tin colloid increased. The residual radioactivity of 188Re–sulfur colloid in disposable polypropylene syringes after injecting mice was high (62.0±7.0%) due to its hydrophobic nature, while that of 188Re–tin colloid was low (2.9±1.6%). Although both 188Re–tin colloid and 188Re–sulfur colloid might be useful for radionuclide therapy, we conclude that 188Re–tin colloid is more advantageous over 188Re–sulfur colloid, due to higher labeling efficiency, control of the particle size, and lower residual activity in the injection syringes.

Samarium 153-labeled hydroxyapatite microspheres for radiation synovectomy in the horse: a study of the biokinetics, dosimetry, clinical, and morphologic response in normal metacarpophalangeal and metatarsophalangeal joints.

To determine the effects of Samarium-153 bound to hydroxyapatite microspheres (153SmM) when injected into the metacarpophalangeal and metatarsophalangeal joints of horses. - Horses were injected with 153SmM in metacarpophalangeal and metatarsophalangeal joints with the diagonal contralateral joints used as untreated controls. Twelve adult horses without pre-existing disease involving the metacarpo/metatarsophalangeal joints. Horses were divided into three groups: high-dose Samarium-153 (12.5 to 17.0 millicurie [mCi]), intermediate dose (6.5 to 12.0 mCi), and low dose (3.5 to 6.0 mCi). Horses were examined daily for 7 days postinjection for clinical abnormalities, lameness, and surface and systemic radiation levels. One horse from each group was euthanatized at 14, 30, and 60 days postinjection and the effects of the 153SmM examined microscopically in the cartilage and synovial membrane. Intraarticular(153)SmM caused inflammation characterized by lameness, effusion, and regional edema for 48 to 72 hours. Minimal levels of active 153SmM were identified in the blood or urine and were well below the maximal tolerance of 1 mCi. Microscopically the radiation caused no effects on the articular cartilage. The synovectomy created was good but not ideal in that some areas did have necrosis into the subintimal regions and a few islands of intact intimal cells persisted. The use of 153SmM is an effective means of targeting the synovial intimal cells with minimal extrasynovial leakage of radiation. The metacarpophalangeal and metatarsophalangeal joints of the horse can be safely treated with 153SmM without damage to the cartilage or significant extracapsular leakage.

Radiation Synovectomy by 166Holmium-Chitosan complex in Collagenase Induced Arthritis of the Knee in the Rabbit

Radiation Synovectomy by 166Holmium-Chitosan complex in Collagenase Induced Arthritis of the Knee in the Rabbit

Experience on the neutron activation of natural/enriched Re, Sm, and Ho nuclides in a reactor for the production of radiotherapeutic radionuclides.

In recent years, much effort has been concentrated on the use of beta-emitting radionuclides for the treatment of various cancers. The reports suggested the application of 186Re and 153Sm as radiotherapeutic radionuclides for the treatment of palliative widespread skeletal metastases, whereas 166Ho was suggested as an agent for radiation synovectomy. Hence, a study on the production of 186Re, 153Sm, and 166Ho radionuclides was carried out by neutron activation of the appropriate target materials using a Pakistan Atomic Research Reactor (PARR-1) at a neutrons flux of 1 x 10(4) n/cm2 s. These radionuclides were then converted to appropriate radiopharmaceuticals for their use on animals and patients. The targets of natural Re (metal), natural Sm2O3, enriched Sm2O3 (99.06%), Sm(NO3)3 (solid), Sm(NO3)3 (liquid), and Ho2O3 were irradiated in the PARR-1. After irradiation, the purity of these radionuclides were checked by a multichannel analyzer, Canberra series 85 (MCA) coupled with HPGe detector and then measured in radioisotope calibrator Capintec ionization chamber model CRC-5RH. The effect of the irradiation time and amount of target material was investigated on the production yields of the radionuclides. The results showed an increase in the specific activity of Re with an increase in the irradiation time from 1 to 72 h, whereas a decrease in the specific activity was observed with increase in the amount of Re from 10 to 100 mg. Similar results were obtained for 153Sm and 166Ho radionuclides. The results further indicated that the specific activity of powder target was much less than the liquid targets for 153Sm. Their conversion to the appropriate radiotherapeutic radiopharmaceuticals were also carried out by investigating the experimental conditions and acceptable quality of 186Re-HEDP and 153Sm-EDTMP complexes were prepared. These complexes were then used on animals and patients which showed good performance.

Application of radioisotopes in the field of nuclear medicine

A comprehensive review has been made to discuss the role of various radionuclides of lanthanide series elements in the field of nuclear medicine. The role of several pharmaceuticals labeled with radiolanthanides and used for investigative purposes like measurement of cerebral blood flow, bone density measurement, bone marrow imaging, etc., have been described. The role of lanthanide radionuclides in radiation synovectomy, radioimmunotherapy, etc., have also been discussed. Methods of preparation of some representative radiopharmaceuticals like153Sm-EDTMP,153Sm-HYP, have been presented. An outline on the production of carrier free radioisotopes of lanthanide series elements has been given.

Activity leakage and radiation exposure in radiation synovectomy of the knee: influence of different therapeutic modalities

In rheumatic diseases, radiation synovectomy is a reliable method. Meanwhile, radiation synovectomy is an outpatient therapy. In addition, combination with arthroscopic synovectomy is an increasing therapeutic modality. In comparison to the hitherto inpatient modality, a greater lymphatic emigration of the radionuclide and, therefore, a higher radiation exposure is possible. In 35 patients we found radionuclide emigration in 17 cases by whole body scintigraphy, resulting in a 50%-percentile with 68.27%-confidence interval of 1.8 (0.45-4.78)% of the injected yttrium-90-activity. Comparison of 3 groups with the above mentioned therapy modalities resulted in no statistical difference (p>0.05). Because of the found radionuclide emigration, a radiation dose of 0. 1 (0.05-0,18) mSv in women and 0.2 (0.1-0.38) mSv in men was calculated. For lymph nodes, liver, spleen and whole body radiation doses of 619 (154-1644) mSv, 62 (15-165) mSv, 62 (15-165) mSv and 37 (9-99) mSv were calculated. Gonadal radiation dose can be neglected and the morbidity rate for tumors because of the whole body radiation dose is low with a value of 0.4 per thousand. Therefore, radiation synovectomy can be used unlimited by patients age and independent of the therapeutic modality.