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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 [ 186 Re] 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., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The aim of this study was to assess the long-term anti-inflammatory effect and safety of 90-Yttrium and 166-Holmium radiosynoviorthesis (RSO) for treating chronic knee synovitis of various origins., Methods: A total of 820 patients were included in this study and were followed up to 10 years after the procedure for objective and subjective changes in signs and symptoms of inflammation., Results: Five years after RSO, excellent and good results were seen in 71% (95% CI 67-74%) of patients. Six, seven, eight and nine years following RSO, efficacy did not decrease significantly. Ten years after RSO, the effectiveness of the therapy fell to 65% (95% CI 59-71%). Overall, 64% of patients did not need another joint puncture ten years after RSO. We achieved excellent to good results at 5 years in 79% of patients with rheumatoid arthritis, 59% with ankylosing spondylitis, and 62% with osteoarthritis. Efficacy was mainly affected by the local X-ray stage of the knee joint. A significant association was also found between the diagnosis of the underlying disease and the success of radiosynoviorthesis. Efficacy, however, was not substantially affected by any of the following factors: the duration of synovitis, the number of punctures before radiosynoviorthesis, the number of intraarticular steroid injections before the procedure, or the number of interventions before radiosynoviorthesis (radiotherapy, surgery)., Conclusions: Radiosynoviorthesis is an effective long-term method of treating chronic synovitis. The treatment showed the most favorable effects in patients with rheumatoid arthritis and those with mild to moderate degenerative osseous changes.

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., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: Author M. Fischer is external medical advisor regarding pharmacovigilance of Curium Germany GmbH, which does not mean any potential conflict of interest regarding this publication. No COI for all other authors., (Thieme. All rights reserved.)

Purpose: Radiosynoviorthesis (RSO) using the intraarticular application of beta-particle emitting radiocolloids has for decades been used for the local treatment of inflammatory joint diseases. The injected radiopharmaceuticals are phagocytized by the superficial macrophages of the synovial membrane, resulting in sclerosis and fibrosis of the formerly inflamed tissue, finally leading to reduced joint effusion and alleviation of joint pain., Methods: The European Association of Nuclear Medicine (EANM) has written and approved these guidelines in tight collaboration with an international team of clinical experts, including rheumatologists. Besides clinical and procedural aspects, different national legislative issues, dosimetric considerations, possible complications, and side effects are addressed., Conclusion: These guidelines will assist nuclear medicine physicians in performing radiosynoviorthesis. Since there are differences regarding the radiopharmaceuticals approved for RSO and the official indications between several European countries, this guideline can only give a framework that must be adopted individually., (© 2021. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objective: To summarise the evidence on intra-articular therapies (IAT) to inform the 2020 EULAR recommendations., Methods: An overview of systematic reviews (SR) including randomised-controlled trials (RCTs) of IAT in adults with arthropathies was performed up to July 2020. Pain, function, and frequency of adverse events were the main efficacy and safety outcomes, respectively. Quality was assessed with the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool., Results: Of 184 references identified, 16 met the inclusion criteria, and a search of their reference lists identified 16 additional SRs. After quality assessment, 29 were finally included. Of these, 18 focused on knee osteoarthritis (KOA), 6 on hip osteoarthritis (HOA), 3 on shoulder capsulitis (SC), and 3 on rheumatoid arthritis. Overall, hyaluronic acid showed a small effect on pain and function in KOA but not in HOA or shoulder capsulitis. Intra-articular glucocorticoids showed a small effect in pain and function in KOA and function in HOA and SC. Platelet-rich plasma showed benefit in pain and function in KOA but not in HOA. Mesenchymal stem cells behaved similarly. Most SR results were of moderate quality and RCTs included often presented a high risk of bias, mainly due to inadequate blinding and heterogeneous results. All interventions were well tolerated with no clear safety differences., Conclusions: This overview underlines that most IAT currently used in KOA, HOA, and SC exert small effects and are well tolerated. However, no firm conclusions can be drawn for inflammatory arthritis due to the limited data found., Competing Interests: Competing interests: SCR-G reports grants from The Spanish Rheumatology Foundation during the conduct of the study, and personal fees from Roche, Sanofi, MSD, UCB-Pharma, Bristol-Myers-Squibb and Novartis and non-financial support from Lilly, Pfizer, Sanofi, MSD, Abbvie, UCB-Pharma, outside the submitted work. MD has received personal fees for advisory boards from Grunenthal, Mallinckrodt and Pfizer, and author royalties from UpToDate, and was an investigator in an AstraZeneca-funded, non-drug study (the ‘Sons of Gout’ study), unrelated to this work. LT has received speakers fee from AbbVie, Janssen, Roche, Novartis, Pfizer, MSD, BMS and GE. FB reports personal fees from Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Serono, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, outside the submitted work. LC declares that her institute receives grants for studies and research courses from Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 90 Yttrium 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.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018. Published by Elsevier Inc.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A vast spectrum of lower limb bone and joint disorders (hip, knee, ankle, foot) present with a common clinical presentation: limping. Too often this symptom generates an inefficient cascade of imaging studies. This review attempts to optimise the diagnostic effectiveness of bone scintigraphy using the hybrid SPECT/CT technique in relation to the diagnostic clues provided by other imaging modalities, discusses the appropriate clinical indications, optimal scintigraphic procedures and illustrates updated image pattern-oriented reporting. Frequent lower limb bone and joint pathologies that can now be reliably diagnosed using hybrid bone SPECT/CT imaging will be reviewed. Bone SPECT/CT can be an effective problem-solving tool in patients with persistent limping when careful history taking, clinical examination, and first-line imaging modalities fail to identify the underlying cause., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: The aim of this retrospective study was to compare the targeting of "pure" osteomyelitis (i.e., without surrounding soft tissue infection) by directly 99mTc-labelled complete immunoglobulin G (IgG) monoclonal antibody (MAb) ([99mTc]besilesomab) and by directly 99mTc-labelled fragment antigen-binding (FAb) MAb ([99mTc]sulesomab) in relation to their kinetic fate. A total of 73 patients with "pure" osteomyelitis were examined with [99mTc]besilesomab, (Scintimun®, IBA/CIS bio international, Saclay, France; N.=38) and [99mTc]sulesomab (LeukoScan®, Immunomedics Inc., Morris Plains, NJ, USA; N.=35)., Methods: Kinetic data were deduced from whole-body and single-photon emission computed tomographic scans, performed 10 minutes to 24 hour p.i. (region-of-interest technique [ROI])., Results: In targeting "pure" osteomyelitis, sensitivities at 1-4 hours were found to be higher for [99mTc]sulesomab (44% and 80% for [99mTc]besilesomab and [99mTc]sulesomab, respectively) but at significantly lower target/background (T/B) ratios than with [99mTc]besilesomab (1.8±0.3 versus 1.4±0.5 for [99mTc]besilesomab and [99mTc]sulesomab respectively; P<0.01). With [99mTc]besilesomab, there was a continuous osteomyelitis uptake over 24 hours, whereas with [99mTc]sulesomab, the maximal uptake occurred mostly within 1-4 hours, with subsequent clearance being slower for antigen-bound activity than for nonspecific background. Hence, diagnosis was possible mostly after 4h with [99mTc]sulesomab but often not before 24 hours with [99mTc]besilesomab, the later increasing significantly (P<0.01) in sensitivity (87% and 84% for [99mTc]besilesomab and [99mTc]sulesomab, respectively)., Conclusions: These results show that the higher sensitivity of [99mTc]sulesomab in osteomyelitis targeting at earlier p.i. times does not rely on an increased antibody uptake but on a more rapid clearance of nonspecific background activity due to faster metabolism and excretion. Intact [99mTc]besilesomab show a slow, continuous uptake, leading to higher T/B at later p.i. times, often beyond the imaging possibilities of 99mTc.

Purpose: The radionuclide bone scan is the cornerstone of skeletal nuclear medicine imaging. Bone scintigraphy is a highly sensitive diagnostic nuclear medicine imaging technique that uses a radiotracer to evaluate the distribution of active bone formation in the skeleton related to malignant and benign disease, as well as physiological processes., Methods: The European Association of Nuclear Medicine (EANM) has written and approved these guidelines to promote the use of nuclear medicine procedures of high quality., Conclusion: The present guidelines offer assistance to nuclear medicine practitioners in optimizing the diagnostic procedure and interpreting bone scintigraphy. These guidelines describe the protocols that are currently accepted and used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.

The skeleton is a potential metastatic target of many malignant tumors. Up to 85% of prostate and breast cancer patients may develop bone metastases causing severe pain syndromes in many of them. In patients suffering from multilocular, mainly osteoblastic lesions and pain syndrome, radionuclide therapy is recommended for pain palliation. Low-energy beta-emitting radionuclides ((153)samarium-ethylenediaminetetrameth-ylenephosphonate (EDTMP) and (89)strontium) deliver high radiation doses to bone metastases and micrometastases in the bone marrow, but only negligible doses to the hematopoietic marrow. The response rate regarding pain syndrome is about 75%; about 25% of the patients may even become pain free. The therapy is repeatable, depending on cell counts. Concomitant treatment with modern bisphosphonates does not interfere with the treatment effects. Clinical trials using a new, not yet approved nuclide ((223)Radium) and/or combinations of chemotherapy and radionuclides are aiming at a more curative approach.

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., (Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Chronic pain is one of the most frequent and distressing symptoms in patients suffering from bone metastases due to malignant disease. Besides pharmacological therapy using analgesics according to the WHO scheme and local surgical or radiotherapeutic treatment options, systemic radionuclide therapy is available, particularly for patients with multilocular metastatic disease. This palliative pain treatment is almost free of severe side effects and is thus indicated as a complementary therapy as part of an interdisciplinary approach in pain treatment. Moreover, preliminary data indicate a favorable cost:utility ratio. Positive clinical effects with marked reduction of pain are described in 70-80% of patients with breast or prostate cancer. However, complete analgesia is uncommon and, thus, most patients require analgesic treatment during the further course of their disease.

Radiosynoviorthesis (RSO) with an yttrium-90 colloid offers a local and minimally invasive therapy for treating inflammatory hypertrophy of the synovial membrane of the knee that has arisen from numerous kinds of disorder: these include rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthropathy, villonodular synovitis and others. There is substantial evidence that this treatment is efficacious and that, in view of the benefits that it offers, its tolerability and safety are very good. Administration should be restricted to patients in whom other therapies (including locally injected corticoids) have failed, and proper attention must be paid to correct administration, including post-treatment immobilization and the co-administration of corticoids, to minimize the risk of leakage and of efflux through the puncture channel.

In the treatment of malignant melanoma, various stage-dependent diagnostic and therapeutic procedures are widely accepted. The situation becomes more complicated in pregnant women due to potential hazardous side effects to the fetus. We report on a 36-year-old woman, who was admitted with a high-risk malignant melanoma on the right cheek. Prior to surgery we performed computed tomography (CT)-scans that were unremarkable with the exception of "two small cysts of the uterus" The primary melanoma was excised and a sentinel node biopsy was performed under general anesthesia using radioactive tracers. Afterwards, adjuvant therapy with interferon alpha 2b was initiated. Five weeks later our patient reported that she was pregnant with twins in their eleventh week of gestation, although she previously denied several questions regarding a potential pregnancy. She declined the offer of an abortion and elected to continue with the interferon treatment against our medical advice. In the 36(th) week of gestation, she developed regional lymph node metastases. Consequently, labor was induced, resulting in the delivery of healthy twins. Six months later our patient developed lung metastases. Despite several chemotherapy regimens, she died one year later. An interdisciplinary approach to obtaining informed consent and managing female high risk melanoma patients with potential or present pregnancy is presented.

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.

Aim: Radiosynoviorthesis using intraarticular injection of beta-emitting radiocolloids is increasingly performed throughout Europe in patients with inflammatory joint disease. It is a cost-effective and safe treatment, local complications are very rare with only eight cases mentioned in the literature so far. No recommendations for therapy of tissue necrosis, infection or thromboembolism after radiosynoviorthesis are available., Methods: Using a standardized questionary, 260 nuclear medicine physicians and 20 medical liability insurances were asked for the kind and frequency of complications after radiosynoviorthesis between 1998 and 2003. The survey was terminated after nine months with a response of only 25.7%., Results: A total of 53 severe complications were documented (28 necroses, 12 thromboses, 13 joint infections). Eight other complications were seen but difficult to correlate directly with radiosynoviorthesis. Tissue necroses from yttrium-90 were successfully treated by surgical excision and closure of the defect. Rhenium-186-induced ulcers healed by hyperbaric oxygen therapy in two cases. Lesions from erbium-169 showed restoration by conservative treatment. Thromboembolic events happened after radiosynoviorthesis in joints of the lower limb only, mostly treated by conventional anticoagulation. Intraarticular infections showed restoration after intraarticular antibiotics in the majority of cases., Conclusion: Severe complications after radiosynoviorthesis seem to be rare. However, because of the low return rate, a reliable frequency cannot be calculated. Nevertheless, important advices regarding treatment concepts can be taken from our data.

The aim of this study was to investigate the in vivo frequency of chromosomal aberrations (primarily dicentric chromosomes and chromatid breaks) potentially induced by (224)Ra alpha-radiation in peripheral lymphocytes. The study was designed to serve as a cytogenetic analysis along with the therapeutic procedure of ankylosing spondylitis patients who were undergoing a treatment with (224)Ra-chloride. The total administered activity was 10 MBq, and the treatment followed a schedule of 10 i.v. injections per week, each with a dose of 1 MBq of (224)Ra. The calculation of absorbed doses delivered to the blood used the models suggested by the ICRP and yielded a value of 4.7 mGy/MBq. The frequency of chromosomal aberrations observed during the course of therapy was related to the blood dose. The frequency of dicentric chromosomes induced in vivo was found to agree well with the corresponding value of dicentrics induced in vitro. However--given that peripheral lymphocytes are in the cell cycle's G(0) stage--an unexpected increase with dose in the yield of chromatid breaks was observed, with about 95% of them occurring in cells without any other chromosome-type aberrations. Reasons for the production of chromatid breaks are discussed.

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.

The aim of the study was to assess the diagnostic value of the sentinel node method in patients suffering from squamous cell carcinoma of the upper aerodigestive tract. In 50 patients with oral, pharyngeal or laryngeal carcinomas staged N0 up to 50 MBq technetium-99m colloid were injected peritumorally. Sentinel nodes were localised using a gamma-probe in the setting of an elective neck dissection. Pathological findings of sentinel nodes and corresponding neck specimens were compared. In 46 patients sentinel nodes were detected. Of these 34 patients were free of metastatic disease in the sentinel nodes and in the neck specimens. In 12 patients clinically occult metastases were found in the sentinel nodes. Three metastases were detected only after additional sectioning of the sentinel nodes. In four patients, a sentinel lymph node could not be localised. Our results support the sentinel node concept in head and neck cancer and a definition of the sentinel nodes as the three nodes with the highest activity. Careful clinical staging of the neck and thorough pathological evaluation of the sentinel nodes are necessary to avoid false-negative results.

Unlabelled: Transplantation of progenitor cells (PCs) has been shown to improve neovascularization and left ventricular function after myocardial ischemia. The fate of transplanted PCs has been monitored by fluorescence labeling or by genetic modifications introducing reporter genes. However, these techniques are limited by the need to kill the experimental animal. The aim of this study was to radiolabel CD34(+) hematopoietic PCs (HPCs) with (111)In-oxine and to evaluate the feasibility of this in vivo method for monitoring myocardial homing of transplanted cells in a rat myocardial infarction model., Methods: Human HPCs were isolated from mobilized peripheral blood and labeled with (111)In-oxine. Labeled HPCs were injected into the cavity of the left ventricle in nude rats 24 h after induction of myocardial infarction (n = 4) or sham operation (n = 4). Scintigraphic images were acquired up to 96 h after HPC injection. After animals were killed, tissue samples of various organs were harvested to calculate tissue-specific activity and for immunostaining., Results: Labeling efficiency of HPCs was 32% +/- 11%. According to trypan-blue staining, viability of radiolabeled HPCs was impaired by 30% after 48 and 96 h in comparison with unlabeled cells, whereas proliferation and differentiation of HPCs was nullified after 7 d, as assessed by colony-forming assays. After injection of HPCs, the specific activity ratio of heart to peripheral muscle tissue increased from 1.10 +/- 0.32 in sham-operated rats to 2.47 +/- 0.92 (P = 0.020) in infarcted rats. However, the overall radioactivity detected in the heart was only about 1%. A transient high lung uptake of 17% +/- 6% was observed within the first hour after infusion of HPCs. At 24 h after injection, the initial lung activity had shifted toward liver, kidneys, and spleen, resulting in an increase of radioactivity in these organs from 37% +/- 6% to 57% +/- 5%., Conclusion: Radiolabeling with (111)In-oxine is a feasible in vivo method for monitoring transplanted HPCs in a rat myocardial infarction model. The potential to detect differences in myocardial homing between infarcted and normal hearts suggests that this method may provide a noninvasive imaging approach for clinical trials using transplanted HPCs in patients. Our findings, however, also demonstrated a negative effect of (111)In-oxine on cellular function, which resulted in complete impairment of HPC proliferation and differentiation. For future trials in stem cell imaging with (111)In-oxine, therefore, it will be mandatory to carefully check for radiation-induced cell damage.

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.

Background: When synovitis is proved, intra-articularly injected beta emitting radionuclides like yttrium-90 ((90)Y) are used to treat the inflamed synovium., Objective: To study the viability, matrix production, and NO production during or after (90)Y treatment of chondrocytes., Methods: Monolayer, alginate, and explant cultures of primary bovine articular chondrocytes as well as synoviocytes were incubated with 0-3 MBq (90)Y/ml medium for four days from culture day 3 onwards. Cell viability was demonstrated by light and electron microscopy or by trypan blue or ethidium bromide/fluorescein diacetate staining, membrane integrity by measurement of lactate dehydrogenase (LDH) activity in the culture supernatants. Biosynthetic activity was demonstrated by incorporation of [(3)H]proline and immunocytochemical staining of collagen type II. NO production was measured with the Griess reagent., Results: In chondrocyte and synoviocyte monolayer cultures radiation caused a dose dependent increase in cell death and membrane destruction within four days. In alginate and explant cultures, where proliferation is low, no significantly increased LDH activity was seen, and cell viability was approximately 100% for up to 14 days after irradiation. Collagen type II expression (alginate) and biosynthetic activity (alginate and explants) were decreased dose dependently while there was an increase in NO production. Light and electron microscopy data showed that five weeks after irradiation all cells in alginate and most cells in explants subjected to 3 MBq (90)Y/ml were dead, whereas after lower amounts of irradiation several morphologically intact cells were found., Conclusions: beta Irradiation may influence the long term maintenance of cartilage tissue or the aetiology of degenerative joint diseases.

Unlabelled: This preliminary treatment trial was performed to evaluate the safety and clinical efficacy of intracavitary therapy with (186)Re-colloid in patients with recurrent otitis media and paranasal sinusitis, resistant to pharmacotherapy and surgical treatment., Methods: Thirty-nine applications of 5-35 MBq (186)Re-colloid into the tympanon and the paranasal sinuses were performed in 6 patients. Biodistribution and biokinetics were studied by gamma-camera imaging. Clinical success was documented 6-20 mo after therapy by each patient's self-evaluation and by rhinootologic follow-up, using a 4-step score., Results: No harmful side effects were seen. There was good-to-excellent clinical improvement with a score of +1.44 +/- 0.5 by each patient's self-evaluation and by physicians scoring of +0.81 +/- 0.9 with only negligible extracranial tracer deposition., Conclusion: This novel treatment option using intracavitary application of (186)Re-colloid in chronic otitis media and sinusitis is safe and effective. The term "radio-tympano-sinu-orthesis" might be proposed analogously to the well-known radiosynoviorthesis.

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.

Unlabelled: The aim of this experimental study was to investigate the myeloprotective potential of amifostine in rabbits receiving high-dose treatment with either (153)Sm-ethylenediaminetetramethylene phosphonate (EDTMP) or (186)Re-hydroxyethylidene diphosphonate (HEDP) and to check for drug interactions impairing the skeletal uptake of these radiopharmaceuticals by amifostine., Methods: To a total of 24 rabbits, we administered 1,000 MBq of either (153)Sm-EDTMP (n = 12) or (186)Re-HEDP (n = 12). Six animals of each group received 500 mg amifostine intravenously 10-15 min before injection of the radiopharmaceutical, whereas the other 6 animals served as controls. Up to 8 wk after treatment, blood samples were collected every 3-5 d to measure platelet and leukocyte counts. Furthermore, whole-body images were acquired at 3 min, 3 h, and 24 h after injection of the radiopharmaceutical to quantify the skeletal uptake., Results: For (186)Re-HEDP, the mean decrease in platelets was significantly less in the amifostine group (35.5% +/- 2.4%) than in the control group (61.3% +/- 5.4%, P < 0.001). Similar results were found for (153)Sm-EDTMP (36.5% +/- 8.3% vs. 52.3% +/- 14.0%, P < 0.05). No significant differences in leukocyte counts were found for (186)Re-HEDP (75.3% +/- 12.3% in the amifostine group and 72.5% +/- 4.1% in the control group, P > 0.05), whereas rabbits treated with (153)Sm-EDTMP plus amifostine showed a significantly greater decrease in leukocytes (69.2% +/- 10.8%) than did the control group (56.6% +/- 4.0%, P < 0.05). Bone uptake in percentage of initial total whole-body activity was significantly decreased in animals treated with amifostine compared with the control groups for both (186)Re-HEDP (15.8% +/- 3.1% vs. 30.9% +/- 1.9%, P < 0.001) and (153)Sm-EDTMP (31.7% +/- 8.9% vs. 44.0% +/- 6.5%, P < 0.05)., Conclusion: For amifostine, we found a highly significant cytoprotective effect on platelets but no leukoprotective effect. The latter probably relies on the intrinsic myelotoxicity of high-dose amifostine, which seemed to potentiate the leukodepression of the radiopharmaceuticals. The lower bone uptake in amifostine-treated animals may be caused by the chemical structure of amifostine, which is a potentially complex-forming compound that may be able to displace bisphosphonates from the rhenium- and samarium-bisphosphonate complexes, resulting in altered biodistribution patterns.

For 12 years, a 26-year-old man had acne conglobata and a non-suppurative diffuse sclerosing osteomyelitis of the mandible as part of a chronic recurrent multifocal osteomyelitis of the sternum, the pelvic bones, and the femoral head, and aseptic arthritis of the knee, the fibulotalar, and the sternoclavicular joints. This fulfills the formal criteria of the SAPHO syndrome. Repeated surgical and antibiotic treatment combined with hyperbaric oxygen caused partial improvement. Complete relief and partial disappearance of the scintigraphic lesions was achieved with long-term corticosteroids, non-steroidal anti-inflammatory drugs, minocycline, and isotretinoin., (Copyright 2001 The British Association of Oral and Maxillofacial Surgeons.)