[Pain reduction by radiosynoviorthesis in rheumatism-induced synovitis of the elbow : Results of a retrospective multicenter data analysis]. / Schmerzreduktion durch Radiosynoviorthese bei rheumatisch bedingter Synovialitis des Ellenbogens : Ergebnisse einer retrospektiven, multizentrischen Datenanalyse.

BACKGROUND: Radiosynoviorthesis (RSO) is a nuclear medical local treatment modality for inflammatory joint diseases. It is indicated in patients with rheumatoid arthritis (RA) in joints with persistent synovitis despite adequate pharmacotherapy. Arthritis of the elbow joint occurs in up to 2/3 of patients with RA. Intra-articular radiotherapy using the beta emitter [186Re] rhenium sulfide leads to sclerosis of the inflamed synovial membrane with subsequent pain alleviation. The clinical efficacy in cubital arthritis, however, has so far only been described in small monocentric studies. OBJECTIVE: The degree of pain alleviation by RSO was analyzed in patients with rheumatoid cubital arthritis, treated in several nuclear medical practices specialized in RSO. MATERIAL AND METHODS: The subjective pain intensity before and after RSO was documented in a total of 107 patients with rheumatic cubital arthritis using a 10-step numeric rating scale (NRS). A difference of ≥ -2 is rated as a significant improvement. Follow-up examinations were done after a mean interval of 14 months after RSO (at least 3 months, maximum 50 months). RESULTS: The mean NRS value was 7.3 ± 2.1 before RSO and 2.8 ± 2.2 after RSO. A significant pain alleviation was seen in 78.5% of all patients treated. The subgroup analysis also showed a significant improvement in the pain symptoms in all groups depending on the time interval between the RSO and the control examination. A significant pain progression was not observed. The degree of pain relief was independent of the time of follow-up. CONCLUSION: Using RSO for local treatment of rheumatoid cubital arthritis leads to a significant and long-lasting pain relief in more than ¾ of the treated patients.

Intra-articular Treatment of Digital Osteoarthritis by Radiosynoviorthesis-Clinical Outcome in Long-term Follow-up.

PURPOSE: This retrospective study analyzed the long-term effects of radiosynoviorthesis (RSO) with special emphasis to local joint pain in patients from 4 different RSO centers in Germany and Austria. METHODS: A total of 168 finger joints in 147 patients with digital joint OA were investigated. The indication for RSO was based on both clinical complaints and a proven synovitis, despite anti-inflammatory pharmacotherapy and previous intra-articular corticosteroid injections. Radiosynoviorthesis was performed according to international guidelines. A numeric visual analog scale (VAS) before and after treatment was used to measure the outcome. Follow-up was done for at least 2 years after treatment, in some patients even over 10 years. RESULTS: Radiosynoviorthesis resulted in a significant reduction of VAS values in most of the patients, lasting for the whole period of follow-up. Two-thirds of the treated joints showed clinically relevant improvement, if a reduction of 30% in VAS values was defined as a reasonable cutoff. The best results were achieved in thumb base joints. CONCLUSIONS: This article confirms that RSO is a suitable treatment option for digital joint OA with a proven synovitis. The analgesic effect is long-lasting and comparable to the success of RSO in patients with rheumatoid arthritis.

[The Baker's cyst - a blunt sword of Damokles in radiosynoviorthesis (RSO)?] / Die Bakerzyste ­ das stumpfe Damoklesschwert bei der Radiosynoviorthese (RSO)?

The existence of a popliteal Baker's cyst was regarded as a contraindication for radiosynoviorthesis of the knee joint since decades. A so-called "ventile mechanism" was discussed leading to a significant concentration of the intraarticularly applied, high energy beta emitting radiopharmaceutical yttrium-90-colloid in the cyst. This cyst arises from a bursa beneath the tendon of the medial head of the gastrocnemius muscle, normally communicating with the knee joint space. Since the cyst wall is much thinner than the knee joint capsule, a radiogenic rupture of the cyst was feared, leading to severe radiogenic necroses of the surrounding soft tissue. Due to this potential hazard, knee joint ultrasound is mandatory prior to radiosynoviorthesis to check for any popliteal cysts. New studies however decline the risk of a radiogenic cyst rupture after an appropriately performed radiosynoviorthesis of the knee joint.In case of a preexistent cyst rupture, the risk of a radiogenic tissue damage remains an issue and magnetic resonance imaging (MRI) is the method of choice to exclude this potential hazard. However, MRI sometimes leads to equivocal results. Scintigraphy of the knee joint after intraarticular application of Tc-99m-nanocolloid offers the possibility to check for the integrity of the Baker's cyst in these patients to be sure that radiosynoviorthesis will not lead to a relevant extraarticular leakage with soft tissue necroses. This study describes the procedure of intracavitary distribution scintigraphy by means of representative case reports.

Intra-articular therapies: patient preferences and professional practices in European countries.

To assess patient perspective and professional practice of intraarticular therapies (IATs) across Europe, an expert international multidisciplinary panel designed two open web-based surveys: one targeting people who had experienced at least two IATs (44 items); and one targeting health care providers (HCPs) (160 items). Surveys were disseminated via patient and professional associations and social media. A descriptive analysis was performed. The surveys were answered by 200 patients and 186 HCPs from 26 countries, showing that IAT is routinely performed by rheumatologists (97%) and orthopaedic surgeons (89%), with specific training being compulsory in a few countries. The most frequent indications for IAT are arthritis (76%), osteoarthritis (74%), crystal arthritis (71%) and bursitis (70%); the most frequently injected joints are knee (78%) and shoulder (70%); and the most used compounds are glucocorticoids. The majority of HCPs report informing patients about side-effects (73%), benefits (72%), and the nature of the procedure (72%), which coincides with 27% of patients reporting that they had not been informed about benefits or potential complications of IATs; 73% of patients had not been asked whether they wanted an anaesthetic. Few HCPs (10%) obtain written consent (56% get oral consent, being mandatory for 32%), a procedure deemed necessary by 41% of the patients. 50% of patients reported a clear benefit of IAT and 20% experienced complications including pain, impaired mobility, rashes, or swelling. In summary, the practice of IAT is variable across Europe, and although patients perceive it as relatively safe and usually effective procedure, some gaps were identified.

EULAR recommendations for intra-articular therapies.

OBJECTIVES: To establish evidence-based recommendations to guide health professionals using intra-articular therapies (IAT) in adult patients with peripheral arthropathies. METHODS: A multidisciplinary international task force established the objectives, users and scope and the need for background information, including systematic literature reviews) and two surveys addressed to healthcare providers and patients throughout Europe. The evidence was discussed in a face-to-face meeting, recommendations were formulated and subsequently voted for anonymously in a three-round Delphi process to obtain the final agreement. The level of evidence was assigned to each recommendation with the Oxford levels of evidence. RESULTS: Recommendations focus on practical aspects to guide health professionals before, during and after IAT in adult patients with peripheral arthropathies. Five overarching principles and 11 recommendations were established, addressing issues related to patient information, procedure and setting, accuracy, routine and special aseptic care, safety issues and precautions to be addressed in special populations, efficacy and safety of repeated joint injections, use of local anaesthetics and aftercare. CONCLUSION: We have developed the first evidence and expert opinion-based recommendations to guide health professionals using IAT. We hope that these recommendations will be included in different educational programmes, used by patient associations and put into practice via scientific societies to help improve uniformity and quality of care when performing IAT in peripheral adult joints.

[RSO in clinical practice: Status in Germany 2020]. / RSO im klinischen Alltag: Statuserfassung in Deutschland 2020.

BACKGROUND: Radiosynoviorthesis (RSO) is a local radionuclide therapy of inflammatory joint diseases, successfully performed since several decades mainly as an outpatient-protocol in ambulatory health care centers or nuclear medicine practices. Despite of long-term experience in some centers, only very few valuable or comparable data about the procedure itself and/or the clinical results of this treatment are available. OBJECTIVES: The aim of this online survey is to assess reliable data of the current status in Germany. MATERIALS AND METHODS: A web-based questionnaire was designed to evaluate the status of RSO in Germany including demographic data, training, pretherapeutic diagnostics, clinical procedures, and follow-up. The survey was distributed via the supplier of RSO-nuclides, national nuclear medicine societies, and personal networks. It was available for 28 days and closed on November 30, 2020. RESULTS: A total of 78 specialists in nuclear medicine answered the questionnaire, which corresponds to a response rate of 23 %. Several differences and concordances in pre-therapeutic diagnostics, in the procedure of RSO itself, and follow-up were documented in this survey for the first time. Most important, less than 70 nuclear medicine specialists in Germany perform more than 75 % of all RSO-procedures and most of them are older than 50 years of age. This implies the urgent need of a dedicated advancement of young academics in nuclear medicine and a professional advanced training in RSO to offer this beneficial treatment to future patients. CONCLUSIONS: To achieve these goals, an association of RSO experts would be useful, through which, among other things, an RSO training curriculum is developed and theoretical and practical trainings are organized. Moreover, possible cooperation agreements between ambulant and inpatient institutions would foster the education of young nuclear medicine specialists interested in RSO.

A prospective observational study on the long-term results of 90Yttrium citrate radiosynoviorthesis of synovitis in osteoarthritis of the knee joint.

OBJECTIVES: Radiosynoviorthesis (RSO) is used for the treatment of inflammatory joint diseases. However, there are no long-term results published comparing it to conservative therapy. Therefore, the aim of this prospective observational study was to evaluate response rates after radionuclide therapy in patients suffering from knee osteoarthritis over a time period of 10 years. METHODS: Radionuclide therapy with intra-articular administration of colloidal 90Yttrium citrate was performed in osteoarthritic patients [Kellgren-Lawrence grades I/II (n = 69) and Kellgren-Lawrence grade III (n = 72)]. RESULTS: In patients with early-stage disease, an excellent/good response with respect to pain, joint mobility, and function was observed in 82.5% for 1 year and in 73.7% for 8 years after therapy. Responses declined to 50% at 10 years post treatment. In grade III patients, an excellent/good response was observed in 45.9%; a decline to 41.2% was observed in the first 8 years. In this group, the number of patients available for follow-up after 9 and 10 years dropped significantly from 51 patients after 8 years to only 30 patients after 9 years, and to nine patients after 10 years. As a result, these response rates were not appraisable. CONCLUSION: Long-term results of radiosynoviorthesis in knee osteoarthritis are excellent/good in many patients. The response rate depends on Kellgren-Lawrence stages, and early-stage radionuclide therapy for osteoarthritis is suggested.

Bone SPECT/CT in Postoperative Spine.

Back pain is a common problem and the diagnosis and treatment depend on the clinical presentation, yet overlap between pain syndromes is common. Imaging of patients with chronic back pain in both pre- and postoperative scenarios include radiological, radionuclide, and hybrid techniques. In general, these techniques have their own advantages and limitations. The aim of surgery is to eliminate pathologic segmental motion and accompanying symptoms, especially pain. However, surgical procedures are not without complications and localizing the cause of the pain is often challenging. Radiobisphosphonate bone SPECT/CT is reported to be useful in evaluating benign orthopedic conditions and it often provides valuable information such as accurate localization and characterization of bone abnormalities. In this review, routinely used spinal surgical techniques and procedures are discussed, as well as the acute and delayed complications related to spinal surgery, the role of conventional imaging, and the potential uses of radionuclide bone SPECT/CT to diagnose pseudoarthrosis, cage subsidence, loosening and misalignment, hardware failure, and postoperative infection.

SPECT/CT in Postoperative Hand and Wrist Pain.

In this review we summarize the current evidence and experience regarding the performance of SPECT/CT in the evaluation of patients with postoperative painful wrist or hand. There is a wide range of operative wrist and hand interventions due to congenital, traumatic, degenerative, or inflammatory diseases. A significant number of patients suffer from pain after operative procedures. Several imaging modalities have been used to evaluate the reason for painful postoperative wrists like standard conventional x-rays, ultrasound, CT, MRI, or bone scintigraphy. In the last decade, bone SPECT/CT has offered a new approach in combining metabolic and morphologic cross-sectional information in patients with painful postoperative wrists and is increasingly used if standard imaging fails to identify the pain generator. SPECT/CT is less hampered by artifacts caused by metallic implants and shows more details of the cortical bone compared with MRI. MRI is generally superior regarding visualization of soft tissue structures like tendons, synovia, cartilage, muscles, and ligaments. SPECT/CT arthrography has been established to enable the assessment of cartilage and ligament tears.

SPECT/CT in Postoperative Painful Hip Arthroplasty.

Consecutive milestones in hip arthroplasty design and surgical technique have contributed to the successful and cost-effective intervention this procedure has become today in maintaining mobility and quality of life in patients with osteoarthritis, fracture, or other hip conditions. With the increasing prevalence of hip joint replacements, the need for improved diagnostic imaging tools to guide revision surgery has risen in parallel. Over the last few years, promising data have emerged on the potential role of bone SPECT/CT imaging in the assessment of patients with recurrent pain after arthroplasty. This review summarizes the trends in hip arthroplasty surgery (partial vs total arthroplasty; cemented vs cementless arthroplasty; resurfacing arthroplasty) and prosthesis design (bearing materials; stem designs) over the last decade. In particular, the impact on the biomechanics and interpretation of bone SPECT/CT findings is discussed, with emphasis on integrative reporting in the following frequently encountered conditions: lysis/aseptic loosening, septic loosening, heterotopic ossification, periprosthetic fracture, tendinopathies, and adverse local tissue reactions. Based on the available literature data, bone SPECT/CT is increasingly being used as second-line imaging modality when conventional investigations are nondiagnostic. Further outcome research is warranted to examine whether this technique could be used earlier in patient management.

SPECT/CT in Postoperative Foot and Ankle Pain.

Postoperative pain is a clinically relevant issue in orthopedic patients, affecting more than 40% 1 year after foot and ankle surgery. Because of the very complex anatomy with many different joints and several motion axes, clinical examination and conventional imaging are sometimes not sufficient to identify a local pain generator. Local uptake of bone-seeking radiopharmaceuticals is known to correlate accurately with sites of pain generating foci and, thus, bone scintigraphy has been an established method to evaluate these respective patients for many years. However, the specificity is rather low if only planar images are acquired. The development of SPECT and especially of hybrid SPECT and CT imaging has significantly enhanced the specificity of this technique. The combination of both functional and morphological imaging, ideally performed with a dedicated SPECT/CT system to minimize misregistration owing to motion artifacts and to enhance image quality by attenuation correction, allows an early and reliable detection of pathologic bone processes, even in patients where radiological imaging with MRI or CT is hampered by metal implants. In diabetic patients with a neuropathic Charcot osteoarthropathy, infection can be differentiated from inflammatory bone alterations (causing bone marrow edema) almost certainly using SPECT/CT with radiolabeled white blood cells and antigranulocyte antibodies, allowing an individual and precise treatment planning either in the initial course of the disease or even after surgery. This article reviews the most frequent clinical challenges in patients after foot and ankle surgery, including a description of the various surgical procedures, the different imaging options with their advantages and disadvantages, and aims to integrate bone SPECT/CT into the clinical diagnostic workup.

SPECT/CT in the Postoperative Painful Knee.

This review summarizes the role of SPECT/CT in patients with a painful postoperative knee and describes typical diagnostic criteria in these patients. Pain after knee surgery is common and is influenced by the underlying pathology, the type of surgery, and the patient. Knee joint-preserving surgery includes osteotomy, ligament reconstruction, meniscus surgery, and cartilage repair procedures, often used in combination. Knee arthroplasty procedures consist of unicondylar, patellofemoral, and primary or revision total knee prosthesis. In patients with pain after knee joint-preserving surgery, MRI remains the reference standard. After ligament reconstruction, CT can evaluate postoperative tunnel positioning, and bone SPECT/CT can contribute by assessing overloading or biodegradation problems. After meniscal or cartilage surgery, SPECT/CT can be particularly helpful to identify compartment overloading or nonhealing chondral or osteochondral lesions as cause of pain. SPECT/CT arthrography can assess cartilage damage at an early stage due to altered biomechanical forces. After corrective osteotomy of the knee, SPECT/CT can reveal complications such as overloading, nonunion, or patellofemoral problems. After arthroplasty, conventional radiographs lack both sensitivity to detect aseptic loosening and specificity in differentiating aseptic from infectious loosening. Secondly, hardware-induced artifacts still hamper CT and MRI, despite improving and increasingly available metal artifact reduction techniques. Bone scintigraphy is a proven useful adjunct to conventional radiography and MRI to reveal the pain generator and is less hampered by artifacts from metallic implants compared with CT and MRI. Nevertheless, the optimal imaging strategy in evaluating complications after knee arthroplasty is still a matter of debate. Although the evidence of the use of BS SPECT/CT is still limited, it is growing steadily. In particular, recent data on specific uptake patterns in tibial and femoral zones after total knee arthroplasty and the impact of integrating biomechanics into the assessment of SPECT/CT appear promising, but more research is needed.

Imaging of acute heart-transplant rejection using 99m-Technetium labelled oligonucleotides against interleukin-2 mRNA in rats.

OBJECTIVES: Today, acute cardiac rejection is detected by endomyocardial biopsy, which harbours many risks. Thus, there is a necessity for less invasive methods. Since interleukin-2 (IL2) is over-expressed in acute graft rejection, we use radioactive DNA-fragments complementary to the mRNA of IL2 to detect graft rejection scintigraphically. METHODS: In a rat model of acute graft rejection, the oligonucleotide sequence complementary to the mRNA of IL2 is labelled with 99m-Technetium and injected intravenously. Scintigraphic and Geiger-counter activity of the transplants are evaluated and correlated with the current rejection classification of the International Society for Heart and Lung Transplantation (ISHLT). RESULTS: From the fourth postoperative day onwards, the scintigraphic images show a significant increase of radioactivity (p<0.05) in the rejected organs than in the accepted grafts. While scintigraphy is not significantly correlated with the standard rejections classification of the ISHLT, there is significant correlation between the ISHLT classification and radioactivity in the Geiger-counter analysis. CONCLUSIONS: Radioactively labelled anti-sense-oligonucleotides against mRNA of IL2 may be a promising approach for the detection of acute transplant rejection in vivo.

A planar water tetramer with tetrahedrally coordinated water embedded in a hydrogen bonding network of [Tc4(CO)12-(mu3-OH)4.4H2O].

A virtually planar water tetramer in which the water molecules are virtually tetrahedrally coordinated could be realized in the solid in a three-dimensional network of [Tc4(CO)12-(mu3-OH)4.4H2O]. The network could be produced by cocrystallization of the new cubane-like cluster [Tc(CO)3-(mu3-OH)]4 and water as a complementary component. The amphiphilic behavior of cluster and water results in a highly ordered three-dimensional network. The complementary components, the water tetramer and the cubic cluster, independently of one another form two interpenetrating tetragonal lattice networks held together exclusively by hydrogen bonds.

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.

Bone uptake studies in rabbits before and after high-dose treatment with 153Sm-EDTMP or 186Re-HEDP.

UNLABELLED: The aim of this animal study was to measure the bone uptake of (99m)Tc-hydroxymethylene diphosphonate (HDP) before and after high-dose treatment with (153)Sm-ethylenediaminetetramethylenephosphonate (EDTMP) or (186)Re-(tin)1,1-hydroxyethylidene diphosphonate (HEDP) to prove or disprove post-therapeutic alterations of bone uptake of radiolabeled bisphosphonates. METHODS: Quantitative bone scanning using 100 MBq (99m)Tc-HDP was performed on 12 rabbits before and 8 wk after radionuclide therapy with 1,000 MBq of either (153)Sm-EDTMP or (186)Re-HEDP. Whole-body images were acquired at 3 min, 3 h, and 24 h after injection, and the activities for the whole body, urinary bladder, and soft tissue were measured by region-of-interest technique. From these data, bone uptake was calculated as initial whole-body activity minus urinary excretion and remainder soft-tissue activity. RESULTS: In animals treated with (153)Sm-EDTMP (n = 6), no differences could be proven for the bone uptake of (99m)Tc-HDP at 24 h after injection before and after therapy (51.1% +/- 5.5% vs. 48.0% +/- 6.1%, P > 0.05). There were also no significant differences for the remainder soft-tissue activities and the urinary excretion rates before and after therapy. Similar results were obtained in rabbits treated with (186)Re-HEDP: Bone uptake (44.8% +/- 6.7% vs. 40.4% +/- 4.9%, P > 0.05) and urinary excretion revealed no significant differences before and after treatment. CONCLUSION: No significant impairment of bone uptake of (99m)Tc-HDP could be observed 8 wk after high-dose radionuclide bone therapy. Because both the biokinetic data obtained for (186)Re-HEDP and (153)Sm-EDTMP and the myelotoxic effects were quite similar in rabbits to those in patients, it seems justifiable to expect the same result (i.e., no significant alteration of bone uptake of radiolabeled bisphosphonates) in patients undergoing a second radionuclide therapy within 2-3 mo after standard treatment with (186)Re-HEDP or (153)Sm-EDTMP.

Myeloprotective effects of different amifostine regimens in rabbits undergoing high-dose treatment with 186rhenium-(tin)1,1- hydroxyethylidene diphosphonate (186Re-HEDP).

The aim of this study is to investigate the myeloprotective effects of different amifostine regimens in rabbits undergoing high-dose treatment with 186Rhenium-(tin)1,1-hydroxyethylidene diphosphonate (186Re-HEDP) and to analyze the impact of amifostine on the bone uptake of the radiopharmaceutical. All animals were treated with 1000 MBq 186Re-HEDP. Group ReA received 500 mg amifostine prior to radionuclide therapy, group ReA3 received 3 x 200 mg amifostine 24 hours and 30 minutes prior to and 24 hours after radionuclide therapy. Group ReC served as control receiving no amifostine. Scintigrams were acquired to quantify the skeletal uptake of 186Re-HEDP, and platelet and leucocyte counts were measured. The mean decrease in platelets was 36% +/- 2%, 37% +/- 3%, and 61% +/- 5% for ReA, ReA3, and ReC, respectively. The decrease in ReC was significantly higher than in amifostine-treated animals with no difference between ReA and ReA3. For the leucocytes the mean decrease was 75% +/- 12%, 82% +/- 5%, and 73% +/- 4%, with no significant differences between the respective groups. Bone uptake of 186Re-HEDP was significantly reduced by 50% in ReA and ReA3 compared to ReC. Thus, the 3-day amifostine regimen had no advantage over the single dose regimen, with both regimens reducing bone uptake and yielding a platelet-protective but no leucoprotective effect.