The EANM guideline for radiosynoviorthesis.

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.

Evaluation of aseptic loosening of knee prostheses by quantitative bone scintigraphy.

UNLABELLED: In not infected knee prostheses bone scintigraphy is a possible method to diagnose mechanical loosening, and therefore, to affect treatment regimes in symptomatic patients. However, hitherto studies showed controversial results for the reliability of bone scintigraphy in diagnosing loosened knee prostheses by using asymptomatic control groups. Therefore, the AIM of our study was to optimize the interpretation procedure and to evaluate the accuracy using results from revision surgery as standard. METHODS: Retrospectively, we were able to examine the tibial component in 31 cemented prostheses. In this prostheses infection was excluded by histological or bacteriological examination during revision surgery. To quantify bone scintigraphy, we used medial and lateral tibial regions with a reference region from the contralateral femur. RESULTS: To differentiate between loosened and intact prostheses we found a threshold of 5.0 for the maximum tibia to femur ratio of the both tibial regions and a threshold of 18% for the difference of the ratio of both tibial regions. Using these thresholds, values of 0.9, 1, 0.85, 1, and 0.94 were calculated for sensitivity, specificity, negative predictive value, positive predictive value, and accuracy, respectively. To get a sensitivity of 1, we found a lower threshold of 3.3 for the maximum tibia to femur ratio. CONCLUSION: Quantitative bone scintigraphy appears to be a reliable diagnostic tool for aseptic loosening of knee prostheses with thresholds evaluated by revision surgery results being the golden standard.

[Radiation synovectomy of the knee joint: Evaluation of bremsstrahlung-detection by using a corpse phantom]. / Radiosynoviorthese des Kniegelenkes: Phantomuntersuchung zur Bremsstrahlenmessung.

AIM: Multiple procedures for the quantification of activity leakage in radiation synovectomy of the knee joint have been described in the literature. We compared these procedures considering the real conditions of dispersion and absorption using a corpse phantom. METHODS: We simulated different distributions of the activity in the knee joint and a different extra-articular spread into the inguinal lymph nodes. The activity was measured with a gamma-camera. Activity leakage was calculated by measuring the retention in the knee joint only using an anterior view, using the geometric mean of anterior and posterior views, or using the sum of anterior and posterior views. The same procedures were used to quantify the activity leakage by measuring the activity spread into the inguinal lymph nodes. In addition, the influence of scattered rays was evaluated. RESULTS: For several procedures we found an excellent association with the real activity leakage, shown by an r(2) between 0.97 and 0.98. When the real value of the leakage is needed, e. g. in dosimetric studies, simultaneously measuring of knee activity and activity in the inguinal lymph nodes in anterior and posterior views and calculation of the geometric mean with exclusion of the scatter rays was found to be the procedure of choice. CONCLUSION: When measuring of activity leakage is used for dosimetric calculations, the above-described procedure should be used. When the real value of the leakage is not necessary, e. g. for comparing different therapeutic modalities, several of the procedures can be considered as being equivalent.

Biological dosimetry after yttrium-90 citrate colloid radiosynoviorthesis.

UNLABELLED: Radiosynoviorthesis (RSO) with the ss-particle-emitting nuclide yttrium-90 is an established concept for the treatment of persistent synovitis of the knee joint. The AIM of this study was to investigate the biological radiation effect on the basis of a characteristic radiation parameter. PATIENTS, METHODS: After RSO procedures with yttrium-90 citrate colloid and subsequent immobilisation of the knee, blood specimens of 10 patients were collected immediately before RSO and 11 to 13 days after the intervention. The yield of dicentric chromosomes in the lymphocytes was determined exclusively in metaphases of the first cell cycle in vitro. In addition, activity leakage was measured by wholebody bremsstrahlung-scintigraphy. RESULTS: No statistically significant increase in the number of dicentric chromosomes (26 before treatment and 34 after treatment) in 20 192 cells analyzed from the 20 blood samples could be found as a result of RSO. However, the analysis of at least 1000 cells per blood sample demonstrates a tendency for a biological radiation effect in the blood of patients on the basis of this characteristic radiation parameter. Two of the 10 RSO patients had undergone a second RSO using yttrium-90 citrate, whereby one patient displayed activity transport out of the knee joint, amounting to 6 MBq. Only for him a radiation effect (about 130 mGy per single RSO) could be calculated by biological dosimetry. CONCLUSION: Since in general, based on the analysis of dicentric chromosomes in at least 1000 lymphocytes per individual, detection limits for groups of persons after long-term exposures to low-LET radiation of 50-100 mGy are possible, we assume that RSO with yttrium-90 should be associated with a low whole-body radiation exposure.

Comparison of meclizine levels in the plasma of rats and dogs after intranasal, intravenous, and oral administration.

Meclizine, used prophylactically for the prevention of motion sickness and vertigo, is presently available only in oral form. We report herein that, when given intranasally, meclizine dihydrochloride is absorbed in rats about half as effectively as when given intravenously, but about six times more effectively than after oral administration, as estimated by the area under the plasma concentration-time curve. The mean times to peak levels in plasma are about 8.5 min after an intranasal dose and 49.0 min after oral delivery. We extended these studies to a second species, the beagle dog, and achieved qualitatively similar results with a new formulation (Mecnazone; Nastech Pharmaceutical Co., Inc.). The fraction absorbed intranasally was about 0.89 that of an equivalent intravenous dose but about four times that of an equivalent oral administration. In these studies, the mean times to peak levels in plasma was 11.9 min after an intranasal dose and 70.0 min after an oral dose. Terminal elimination kinetics were the same for all routes within each species. Intranasal delivery of meclizine therefore appears to be superior to the oral route for the more rapid achievement of substantial levels in plasma at a reduced dose.

Drug interactions I: detection of inorganic nitrite in organic nitrate esters under acidic conditions simulating the human stomach.

Both unformulated (bulk) and formulated (drugs) organic nitrate esters (isosorbide dinitrate, nitroglycerin, and pentaerythritol tetranitrate) were studied in the presence and absence of hydrochloric acid to determine if they could be sources of nitrite (and therefore lead to nitrosamine formation) under acidic conditions similar to those found in the stomach. The presence and generation of nitrite ion was detected by a modification of the Griess reaction. Bulk isosorbide dinitrate and nitroglycerin were found to be contaminated with 13.8-121.4 mumoles of inorganic nitrite per mole of nitrate ester. In addition, in the presence of hydrochloric acid, these preparations generated 0.52-1.18 mumoles of inorganic nitrite/mole of nitrate ester/min. Unformulated nitroglycerin generated nitrite at a rate roughly twice that of isosorbide dinitrate. In contrast, no evidence for nitrite contamination or generation by pentaerythritol tetranitrate was found. Tablets and capsules of isosorbide dinitrate contained approximately 27-216 mumoles of nitrite/mole of nitrate ester and, in the presence of hydrochloric acid, generated an average of 0.55 mumole nitrite/min. For isosorbide dinitrate, this rate was similar for bulk and formulated drug. In comparison to isosorbide dinitrate, the amount of nitrite initially present in tablets and capsules of nitroglycerin varied more widely (approximately 25-2290 mumoles nitrite/mole of nitrate ester), and in this case nitrite was generated at higher rates than unformulated drug averaging approximately 4.7 mumoles nitrite/mole of nitrate ester/min. Contrary to a literature report, we found that nitrate ion is not reduced to nitrite by hydrochloric acid (pH 1-3).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of HIG scintigraphy and bloodpool scintigraphy using HDP in arthritic joint disease.

AIM: Because of a similar tracer accumulation, we assumed to get the same information about synovitis in arthritic joint disease with HIG scintigraphy and bloodpool scintigraphy using HDP. Therefore, we compared retrospectively 23 patients. METHODS: In HIG scintigraphy, synovitis was diagnosed according to increasing activity from early to late image. In bloodpool scintigraphy according to an increased activity in comparison to the surrounding tissues. RESULTS: In 694 joints comparison of both scintigraphic modalities was possible, resulting in a 2 x 2 kappa coefficient of 0.93 or 0.97 by using late-phase bone scintigraphy as an anatomical marker. For intra- and interobserver agreement, 2 x 2 kappa coefficients of 0.93 and 0.88 in HIG scintigraphy, respectively 0.96 and 0.90 in blood-pool scintigraphy were calculated. CONCLUSION: This study shows an excellent agreement in the visualization of synovitis by HIG and bloodpool scintigraphy. Because of its higher objectivity and lower cost, investigation of synovitis should be performed by bloodpool scintigraphy.

[Antigranulocyte scintigraphy of septic loosening of hip endoprosthesis: effect of different methods of analysis]. / Antigranulozytenszintigraphie bei septischer Hüft-Endoprothesen-Lockerung: Einfluss unterschiedlicher Auswertemethoden.

AIM: Diagnosis of infection with help of antigranulocyte scintigraphy near body stem is difficult because of contemporary visualisation of bone marrow. Therefore, we investigated, whether it is possible to improve the accuracy in diagnosing septic loosening of hip endoprosthesis by changing the analyzing methods. METHODS: In 28 patients, the results of a visual interpretation of late scan, a visual interpretation and a quantitative interpretation of time-activity-course were compared. These results were verified by histology respectively microbiology. RESULTS: Histological and microbiological verification found 14 septic loosening and 14 aseptic loosening of the hip prothesis. Therefore, sensitivity, specificity, negative and positive predictive value for the visual interpretation of late scan were 0.86, 0.57, 0.80 and 0.67. For visual and quantitative interpretation of time-activity-course we found 0.86, 0.79, 0.85 and 0.80 respectively 1, 0.93, 1, 0.93. For interobserver agreement we found kappa coefficients of 0.28 +/- 0.2 for visual interpretation of late scan, 0.48 +/- 0.17 for visual interpretation and 1.0 +/- 0 for quantitative interpretation of time-activity-course. CONCLUSION: In all investigated values quantitative interpretation of time-activity-course was superior to the other analyzing methods. Therefore, antigranulocyte scintigraphy for septic loosening of hip endoprosthesis should be interpreted quantitatively.

Thyroid disorders in female patients with ankylosing spondylitis.

The association between rheumatological and thyroid disorders has long been known, the most common being the association of rheumatoid arthritis and autoimmune thyroiditis. Little is known as to possible thyroid involvement in ankylosing spondylitis (AS). In 22 female patients with AS and 22 healthy age-matched control subjects parameters of thyroid gland function, rheumatic activity, as well as a subtle drug anamnesis of the rheumatic medication, and an ultrasonographic examination of the thyroid gland were determined. Thyroid function was tested by intravenous injection of 400 microg thyrotropin-releasing hormone (TRH). In parallel basal levels of reverse-T3 (rT3), calcium and anti-thyroid antibodies were estimated. In the AS-group an enlarged thyroid volume was seen in 10 cases, basal FT4, FT3 and TT3 were significantly lower, TSH and TT4 were found to be in the normal range and rT3 was significantly increased. The prevalence of anti-thyroid antibodies was significantly higher in the AS-group. The AS-patients responded as well as the controls with thyroid hormone secretion to TRH, within an observation period of 2 hours. No differences were observed in TSH response. Free serum calcium showed in both groups no significant difference. To summarize our results, female patients with AS showed a

The role of magnetic resonance imaging and scintigraphy in the diagnosis of pathologic changes of the mandible after radiation therapy.

A prospective study of 85 patients with oral cancer, treated with high-dose radiation therapy, was performed to assess the value of magnetic resonance imaging (MRI) and scintigraphy for diagnosis of pathologic changes in the mandible. During postradiotherapeutic monitoring, radiation osteomyelitis occurred in 12 cases, tumor recurrences infiltrating the mandible in five cases, and progressive periodontal disease in nine cases. MRI permitted early diagnosis of radiation osteomyelitis in 11 out of 12 cases; only two cases were false positive. In scintigraphy with 99mTc-HDP, all alterations of the mandible, such as osteoradionecrosis, tumor infiltration, and periodontitis, showed a high uptake, resulting in a sensitivity of up to 100%, but a low specificity of 57%. Scintigraphy permitted assessment of the extension and location of the lesions. Both methods were superior to conventional radiography and clinical examination and should be integrated into a comprehensive follow-up program after radiation therapy.

[99mTc-MIBI scintigraphy of hypofunctional thyroid nodules. Comparison of planar and SPECT imaging]. / 99mTc-MIBI-Szintigraphie hypofunktioneller Schilddrüsenknoten. Vergleich von planarer und tomographischer Technik.

UNLABELLED: 99mTc-MIBI-scintigraphy allows to assess the dignity of hypofunctional thyroid nodules. A concordant pattern in MIBI- and pertechnetate-scintigraphy excludes malignancy with high accuracy. For increased MIBI-uptake histological evaluation is advised. The assessment of MIBI-isointense nodules is discussed controversially. Objective of our study was to analyse the prevalence of malignancy for isointense nodules and the diagnostic accuracy of image acquisition in SPECT-technique. PATIENTS, METHODS: MIBI-scintigraphies were analysed retrospectively. Imaging was performed 60 min after intravenous injection of 510 MBq 99mTc-MIBI. Thyroid nodules were assessed as hypo-, iso- or hyperintense compared to the paranodular tissue. RESULTS: 83 of 225 patients underwent thyroid surgery (age 48.6 ± 12.6 years, 72% women). In 12 (14.5%) cases a papillary carcinoma was diagnosed. In planar imaging 12, 34 and 37, in tomographical imaging 16, 21 and 46 nodules, respectively, were classified as hypo-, iso- oder hyperintense. Among hypo-, iso- and hyperintense nodules in planar imaging 1, 5 and 6 carcinomas were found, resp. In tomographical imaging no, 4 and 8 carcinomas were found, respectively. Classification of iso- and hyperintense nodules as "suspicious for malignancy" showed for planar imaging a sensitivity, specificity, NPV and PPV of 91.7, 15.5, 91.7 and 15.6%, for tomographical imaging of 100, 22.5, 100 and 17.9%, respectively. CONCLUSION: Hypofunctional thyroid nodules with iso- and hyperintense MIBI-Uptake have a comparable prevalence of malignancy. Image acquisition in SPECT-technique results in improved diagnostic sensitivity and negative predictive value.

Thyroiditis de Quervain. Are there predictive factors for long-term hormone-replacement?

BACKGROUND: Subacute thyroiditis is a usually self-limiting disease of the thyroid. However, approximately 0.5-15% of the patients require permanent thyroxine substitution. Aim was to determine predictive factors for the necessity of long-term hormone-replacement (LTH). PATIENTS, METHODS: We retrospectively reviewed the records of 72 patients with subacute thyroiditis. Morphological and serological parameters as well as type of therapy were tested as predictive factors of consecutive hypothyroidism. RESULTS: Mean age was 49 ± 11 years, f/m-ratio was 4.5 : 1. Thyroid pain and signs of hyperthyroidism were leading symptoms. Initial subclinical or overt hyperthyroidism was found in 20% and 37%, respectively. Within six months after onset 15% and 1.3% of the patients developed subclinical or overt hypothyroidism, respectively. At latest follow-up 26% were classified as liable to LTH. At onset the thyroid was enlarged in 64%, and at latest follow-up in 8.3%, with a significant reduction of the thyroid volume after three months. At the endpoint the thyroid volume was less in patients in the LTH group compared with the non-LTH group (41.7% vs. 57.2% of sex-adjusted upper norm, p = 0.041). Characteristic ultrasonographic features occurred in 74% of the patients in both lobes. Serological and morphological parameters as well as type of therapy were not related with the need of LTH. CONCLUSIONS: In this study the proportion of patients who received LTH was 26%. At the endpoint these patients had a lower thyroid volume compared with euthyroid patients. No predictive factors for LTH were found.

Biological dosimetry after radiosynoviorthesis with rhenium-186 sulphide and erbium-169 citrate.

UNLABELLED: Radiosynoviorthesis (RSO) with the nuclides rhenium-186 sulphide (186Re) and erbium-169 citrate (169Er) is an established concept for the treatment of persistent synovitis of medium and small sized joints. THE AIM of the present studies was to investigate the biological radiation effect based on analysing chromosome aberrations. PATIENTS, METHODS: Immediately before and 17 to 19 days (186Re) or 45 to 50 (169Er) days after RSO with 186Re or 169Er colloid and subsequent immobilisation of the treated joint, blood samples of a total of 23 patients were collected. The yield of dicentric chromosomes in lymphocytes was determined exclusively in metaphases of the first cell cycle in vitro. In addition, for 186Re the activity leakage was measured three days after RSO by whole-body scintigraphy. RESULTS: No statistically significant increase in the number of dicentric chromosomes (40 and 88 before and 59 and 105 after treatment with 186Re and 169Er, respectively) in a total of 47017 cells analysed from 46 blood samples could be found as a result of RSO. For 186Re an activity leakage of 3.9%±7% with a maximum of 23.4% corresponding to an effective dose of 2.8±4.5 mSv , respectively 13.8 mSv, was determined. Also in the case of the maximum leakage no significant increase of dicentric chromosomes were detected. CONCLUSIONS: No significant biological radiation effect can be detected after RSO with 186Re and 169Er, also in cases of high leakage. Therefore, RSO can be classified as a save therapeutic procedure without a relevant radiation risk.

Radiosynoviorthesis of medium-sized joints with rhenium-186-sulphide colloid: a review of the literature.

Hypertrophy and inflammation of the synovium with various underlying pathologies - such as rheumatoid arthritis, osteoarthritis, haemophilia and spondyloarthropathy - can be treated successfully by radiosynoviorthesis (RSO). For medium-sized joints (shoulder, elbow, wrist, hip and ankle), the radionuclide of choice is rhenium-186. We review the evidence for the efficacy of this local, relatively non-invasive therapy and evaluate its benefits and risks. We conclude good evidence of rhenium-186 RSO in rheumatoid arthritis and haemophilic arthropathy. In the remaining pathologies, up to now, the therapeutic efficacy has not been confirmed by today's most stringent criteria for clinical studies. The available data support rhenium-186 RSO as a suitable second-line treatment for patients in whom other therapies (including locally injected corticoids) have failed, as long as proper attention is paid to correct administration - including post-treatment immobilization and the co-administration of corticoids.

The effect of the beta-emitting yttrium-90 citrate on the dose-response of dicentric chromosomes in human lymphocytes: a basis for biological dosimetry after radiosynoviorthesis.

The production of dicentric chromosomes in human lymphocytes by beta-particles of yttrium-90 (Y-90) was studied in vitro to provide a basis of biological dosimetry after radiosynoviorthesis (RSO) of persistent synovitis by intra-articular administration of yttrium-90 citrate colloid. Since the injected colloid may leak into the lymphatic drainage exposing other parts of the body to radiation, the measurement of biological damage induced by beta-particles of Y-90 is important for the assessment of radiation risk to the patients. A linear dose-response relationship (alpha = 0.0229 +/- 0.0028 dicentric chromosomes per cell per gray) was found over the dose range of 0.2176-2.176 Gy. The absorbed doses were calculated for exposure of blood samples to Y-90 activities from 40 to 400 kBq using both Monte Carlo simulation and an analytical model. The maximum low-dose RBE, the RBE(M) which is equivalent to the ratio of the alpha coefficients of the dose-response curves, is well in line with published results obtained earlier for irradiation of blood of the same donor with heavily filtered 220 kV X-rays (3.35 mm copper), but half of the RBE(M) relative to weakly filtered 220 kV X-rays. Therefore, it can be concluded that for estimating an absorbed dose during RSO by the technique of biological dosimetry, in vitro and in vivo data for the same radiation quality are necessary.

[Correction of the inclination of the condylar guidance by changing the Bennett angle on the Dentatus articulator]. / Zur Korrektur der Kondylarbahnneigung nach Veränderung des Bennettwinkels im Dentatus-Artikulator.

Since there is an interrelationship between construction-related inclination of condylar guidance and the Bennett angle with the Dentatus articulator, Lauritzen suggested that the inclination of condylar guidance be adjusted 1 degree in the opposing direction for every 5 degrees alteration in the Bennett angle. This method was rejected because calculations of the interdependence of condylar guidance and Bennett angle showed the results, in some cases, to be worse than when the angle was not adjusted. An exact correction procedure was described.

[Effects of projection errors on the pantographic diagnosis of TMJ dysfunction]. / Einfluss von Projektionsfehlern auf die pantographische Diagnostik bei gestörter Kiefergelenkfunktion.

Extraoral recording methods are bound to produce geometric projection errors. Mirror projections of the curvatures on both sides are a particular problem in clicking joints, thus complicating diagnosis. With the aid of magnetic resonance tomography it has been demonstrated in clinical examples that misinterpretations of the recordings can be avoided by means of computer-supported measuring systems providing accurate projection error correction. Furthermore, it is important that diagnosis be based not only on the usual sagittal plane recordings but also on additional information from the horizontal and frontal planes. Magnetic resonance tomography is then used to confirm the eccentric disc luxation established with the aid of the electronic recordings.