[Indications and results of radioiodine treatment of differentiated thyroid cancer]. / Indikationen und Ergebnisse der Radiojodtherapie beim differenzierten Schilddrüsenkarzinom.

BACKGROUND: Malignant tumors of the thyroid gland are the most frequent malignant endocrine neoplasms, comprising approximately 1% of all malignant tumors. In recent years there has been a clear rise in the incidence of differentiated thyroid carcinomas (DTC), especially small papillary carcinomas. OBJECTIVE: Indications for and results of radioiodine treatment (RAI) of DTC. MATERIAL AND METHODS: A review of the current literature and guidelines of RAI in DTC was carried out. RESULTS: The use of RAI is the most important adjuvant treatment option for DTC and is generally well-tolerated. CONCLUSION: Due to the combination of surgery and RAI the DTC has a very good prognosis compared with other cancers, with an average survival rate of more than 90%.

Co-morbid obsessive-compulsive disorder and depression: a Bayesian network approach.

BACKGROUND: Obsessive-compulsive disorder (OCD) is often co-morbid with depression. Using the methods of network analysis, we computed two networks that disclose the potentially causal relationships among symptoms of these two disorders in 408 adult patients with primary OCD and co-morbid depression symptoms. METHOD: We examined the relationship between the symptoms constituting these syndromes by computing a (regularized) partial correlation network via the graphical LASSO procedure, and a directed acyclic graph (DAG) via a Bayesian hill-climbing algorithm. RESULTS: The results suggest that the degree of interference and distress associated with obsessions, and the degree of interference associated with compulsions, are the chief drivers of co-morbidity. Moreover, activation of the depression cluster appears to occur solely through distress associated with obsessions activating sadness - a key symptom that 'bridges' the two syndromic clusters in the DAG. CONCLUSIONS: Bayesian analysis can expand the repertoire of network analytic approaches to psychopathology. We discuss clinical implications and limitations of our findings.

Peace of mind for patients with differentiated thyroid cancer?

UNLABELLED: Differentiated thyroid carcinomas (DTC) have an excellent prognosis, with 10-year overall survival rates over 90%. In addition, DTC patients benefit from their lifelong medical surveillance. The AIM of the study was to compare the patients' overall survival with that of a matched general population. PATIENTS AND METHODS: We have analyzed 1497 consecutive patients with DTC, who underwent radioiodine therapy in Münster, Germany, according to international standards. We classified our patients according to the current 7th edition of the UICC (Union Internationale Contre le Cancer) classification and we compared the overall survival of the patients with the expected survival based on age and sex of the general population as provided by the Federal Statistical Office, Germany. RESULTS: There were no significant differences in overall survival rates between DTC patients of the cohort in stages I to IVa compared to the expected survival based on age and sex of the general population. However, patients in stage IVc showed a significantly worse overall survival rate using the log-rank test (p < 0.0001). CONCLUSION: Patients with DTC showed excellent overall survival rates in stages I, II, III and IVa. All patients, except for those in stage IVc (M1 ≥ 45 years), had overall survival rates similar to the general population.

Biomechanical comparison of forward and lateral lunges at varying step lengths.

AIM: Lunges are commonly included in rehabilitation and strength training programs; however limited information regarding differences between lateral and forward lunges with varying step lengths in young adults exists. The current study compared sagittal plane joint kinematics and kinetics between forward and lateral lunges using self-selected and standardized (60% height) step lengths. METHODS: Thirty-two young adults (16 men, 16 women) completed six lunges of each direction/distance combination while stepping (dominant) limb ankle, knee, and hip peak flexion and net joint extensor moment impulse were quantified. RESULTS: While lateral direction (P=0.063) step lengths were statistically equal between self-selected and standardized lunges, forward self-selected distances were 10% less than the standardized (P<0.001). Compared to forward lunges, lateral lunge ankle flexion was 83.5% greater (P<0.001) for standard and 55.3% greater (P<0.001) for self-selected distances. Knee flexion was 12.8% greater (P<0.001) during forward lunges compared to lateral lunges, with no significant hip direction differences. Ankle impulse during the lateral lunges was 71.3% greater (P<0.001) compared to forward lunges. Lateral lunge knee impulse was 47.6% greater (P<0.001) for standardized and 16.9% greater (P=0.001) for self-selected distances compared to forward lunges. Forward lunge hip impulse was 64.5% greater for the standardized (P<0.001) and 44.6% greater for self-selected (P<0.001) distances compared to lateral lunges. CONCLUSION: Forward lunges, particularly using 60% body height step length, appear to place the greatest demands on the hip extensors. Lateral lunges prompted greater ankle flexion and greater ankle and knee extensor kinetic contributions. These data provide rationale for lunge variation selection for young adults.

Diagnostic value and therapeutic impact of (18)F-FDG-PET/CT in differentiated thyroid cancer. Results of a German multicentre study.

UNLABELLED: The clinical significance of (18)F-FDG-PET/CT in the follow-up of patients with differentiated thyroid carcinoma was evaluated and the results were compared with those of (18)F-FDG-PET, (131)I-whole-body scintigraphy including SPECT/CT (WBS) and ultrasound. In addition, it was the aim to investigate the impact of (18)F-FDG-PET/CT on the therapeutic management. PATIENTS, METHODS: 327 patients (209 women, 118 men; mean age 53 ± 18 years) with differentiated thyroid cancer (242 papillary, 75 follicular, 6 mixed, 1 Hürthle cell and 3 poorly differentiated tumours) were analyzed retrospectively at four tertiary referral centres. 289 (18)F-FDG-PET/CT and 118 (18)F-FDG-PET studies were performed in these patients between 2007 and 2010. In addition, an overall clinical evaluation was performed, including cytology, histology, thyroglobulin level, ultrasound, WBS, and subsequent clinical course in order to compare the molecular imaging results. Finally, the change in therapeutic management due to findings of (18)F-FDG-PET/CT was investigated. RESULTS: The sensitivity of (18)F-FDG-PET/CT was 92%, the specificity was 95%. Sensitivity and specificity of (18)F-FDG-PET alone were 67% and 93%, respectively. WBS showed a sensitivity of 65% and a specificity of 94%. The corresponding values of ultrasound were 37% and 94%, respectively. The sensitivity of (18)F-FDG-PET/CT in the group of patients with a negative WBS (n=194) amounted to 96%. When (18)F-FDG-PET/CT and WBS were considered in combination, tumour tissue was missed in only 2 out of 133 patients; when (18)F-FDG-PET and WBS were combined, tumour tissue was missed in 1 out of 24 patients. (18)F-FDG-PET/CT resulted in management change in 43% (n=57/133) with a decision on surgical approach in 20% (n=27/133). CONCLUSIONS: (18)F-FDG-PET/CT is superior to (18)F-FDG-PET alone in patients with differentiated thyroid cancer and has a direct impact on the therapeutic management of patients with suspected local recurrence or metastases, particularly in those with negative WBS.

Radioiodine remnant ablation in differentiated thyroid cancer after combined endogenous and exogenous TSH stimulation.

AIM: Radioiodine remnant ablation (RRA) after (near-)total thyroidectomy (TE) is a key element in patients with differentiated thyroid cancer (DTC). The use of exogenous TSH stimulation (rhTSH) prior to RRA has shown promising results as compared to conventional thyroid hormone withdrawal (THW). As yet, the efficacy of RRA after brief THW and single rhTSH administration has not been assessed. PATIENTS, METHODS: The study sample comprised 147 patients with DTC referred to our center between May 2008 and September 2010. All patients received TE with subsequent RRA. None of these 147 patients had evidence of distant metastasis. 93 patients had endogenous TSH stimulation 4-5 weeks after surgery (group I) and twenty-six received two rhTSH injections (group II). 28 patients were treated with a single rhTSH injection after a brief THW (group III). RRA-Efficacy was assessed three months after therapy by diagnostic whole-body scan and measurement of the tumour marker thyroglobulin (Tg) under TSH stimulation. RESULTS: Three categories of success were defined for remnant ablation. Based on the definition of successful remnant ablation no visible uptake and a Tg ≤ 2.0 ng/ml (category 1) was seen in 62/93 patients in group I, in 17/26 patients in group II (p = n.s.) and in 12/28 patients in group III (p < 0.05). Visible radioiodine uptake and a Tg ≤ 2.0 ng/ml (category 2) was seen in 16/28 patients of group III and thus significantly more frequent than in group I (28/93 patients) (p < 0.01). However, patients in group III (16/28 patients) and group II (8/26 patients) showed no significant difference in this category (p = n.s.). Visible radioiodine uptake and a Tg > 2.0 ng/ml (category 3) was found in 3/93 patients in group I and 1/26 patients in group II but in no patient in group III. CONCLUSION: The third strategy of remnant ablation using a single injection of rhTSH after a brief THW period resulted in a significant higher rate of patients with residual uptake in the thyroid bed and a Tg level below 2 ng/ml three months after remnant ablation in comparison to THW. However, the overall efficacy of the third protocol was not significantly different as compared to two rhTSH injections. Under the aspect of the supply shortage of rhTSH the combined endogenous and exogenous TSH stimulation may be an attractive alternative for remnant ablation in differentiated thyroid cancer.

Therapeutic strategy of papillary microcarcinoma of the thyroid gland: a nuclear medicine perspective.

According to the literature, the prevalence of papillary thyroid microcarcinoma (PTMC) is increasing. To date, PMTC account for up to 30% of all differentiated thyroid cancers. Patients with PTMC have an excellent prognosis with a normal life expectancy. Because of the differential definitions of the PTMC, the therapeutic approaches of the national Scien-tific Societies have not been standardized. The therapeutic algorithms have to be adjusted with regard to thyroid surgery, radioiodine ablation and thyrotropin-suppressive therapy as well as follow-up. Recently, the Therapy Committee of the European Society of Nuclear Medicine (EANM) has recommended a risk-adapted therapy and follow-up. Risk factors which require a more aggressive therapeutic approach are multifocality, thyroid capsule infiltration, evidence of locoregional or distant metastasis and unfavourable histology. It was the aim of this review to evaluate the current therapeutic concepts in patients with PTMC from a nuclear medicine perspective.

Vertical leg stiffness following ankle taping and bracing.

This study sought to determine if prophylactic ankle taping and bracing influenced vertical leg stiffness during hopping. Twenty healthy and physically active participants completed testing under three ankle stabilizer conditions, ankle tape, semi-rigid ankle brace or control (no stabilizer) during three separate sessions. Immediately following stabilizer application, participants completed an exercise bout prior to completing the hopping. Vertical ground reaction forces were collected during the hopping and were used to calculate vertical leg stiffness. No significant changes in vertical leg stiffness were revealed. These results are likely attributable to the exercise bout causing sufficient loosening of the stabilizers, concurrent proximal joint compensations and/or the possibility that the effect of ankle stabilizers on shock absorption during hopping is more subtle than the effects revealed during drop landings.

Multimodality molecular imaging--from target description to clinical studies.

This highlight lecture was presented at the closing session of the Annual Congress of the European Association of Nuclear Medicine (EANM) in Munich on 15 October 2008. The Congress was a great success: there were more than 4,000 participants, and 1,597 abstracts were submitted. Of these, 1,387 were accepted for oral or poster presentation, with a rejection rate of 14%. In this article a choice was made from 100 of the 500 lectures which received the highest scores by the scientific review panel. This article outlines the major findings and trends at the EANM 2008, and is only a brief summary of the large number of outstanding abstracts presented. Among the great number of oral and poster presentations covering nearly all fields of nuclear medicine some headlines have to be defined highlighting the development of nuclear medicine in the 21st century. This review focuses on the increasing impact of molecular and multimodality imaging in the field of nuclear medicine. In addition, the question may be asked as to whether the whole spectrum of nuclear medicine is nothing other than molecular imaging and therapy. Furthermore, molecular imaging will and has to go ahead to multimodality imaging. In view of this background the review was structured according to the single steps of molecular imaging, i.e. from target description to clinical studies. The following topics are addressed: targets, radiochemistry and radiopharmacy, devices and computer science, animals and preclinical evaluations, and patients and clinical evaluations.

Non-invasive approaches to visualize the endothelin axis in vivo using state-of-the-art molecular imaging modalities.

The endothelin axis plays a major role in cardiovascular diseases and a number of human cancers. This review summarizes the work that has been published in the past ten years using labeled endothelin receptor ligands for the visualization of endothelin receptor expression in vivo.

Risk-profile and outcome of small papillary and follicular thyroid carcinomas (

AIM: According to the procedure guidelines of the German Society of Nuclear Medicine no radioiodine ablation is necessary in patients with papillary microcarcinomas in case of limited surgical resection. Few data are available with respect to the optimal management of patients with small follicular thyroid carcinomas. It was the aim to compare risk-profile and outcome of patients with small papillary (PTC) and follicular thyroid carcinomas (FTC)

Small animal PET in preclinical studies: opportunities and challenges.

The process of drug and molecular imaging development is strongly influenced by the revolution of non-invasive imaging techniques. Small animal positron emission tomography (PET) has the potential to accelerate and streamline drug and molecular imaging discovery and development by preselection of suitable candidate molecules. Due to its significantly improved spatial resolution and its quantitative nature, compared to other techniques small animal PET can be employed to bridge the in vitro, through to preclinical and clinical imaging in humans.

Non-invasive molecular imaging of beta-adrenoceptors in vivo: perspectives for PET-radioligands.

Recently, the spectrum of molecular imaging devices such as positron emission tomography (PET) was further expanded by the now clinically available combined imaging modalities such as PET-CT and the preclinically used small animal PET scanners. These are powerful tools that can bridge the gap between preclinical and clinical evaluation studies of new radiotracers for molecular imaging of healthy and diseased states in vivo. The beta-adrenoceptor (beta-AR) radioligands discussed in this review represent a class of molecular probes for the non-invasive in vivo assessment of beta-AR density eg. in the heart with PET. The beta-AR radioligands (S)-[11C]CGP 12177 (1) or (S)-[11C]CGP 12388 (2) are currently investigated in clinical studies with PET. Additionally, subtype-selective beta1-AR radioligands are used in preclinical research which show potential for the diagnostics of the "beta1-AR organ" as such the heart can be defined. Non-invasive quantification of beta-ARs could facilitate the accurate choice and control of therapeutic interventions. Here we summarize the state-of-the-art of the radiochemistry of radioactive beta-AR radioligands.

[High non-specific binding of the beta(1) -selective radioligand 2-(125)I-ICI-H]. / Hohe unspezifische Bindung des beta(1)-selektiven Radioliganden 2-(125)I-ICI-H.

AIM: As results of cardiac biopsies suggest, myocardial beta(1) -adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac beta(2)-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess beta-adrenoceptors non-invasively. Among the novel racemic analogues of the established beta(1)-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to beta(1)-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective beta(1)-adrenergic radioligand in cardiac imaging. METHODS: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac beta-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-(125)I-ICI-H from the silylated precursor 2-SiMe(3)-ICI-H was established. The specific activity was 80 GBq/ micro mol, the radiochemical yield ranged from 70 to 80%. RESULTS: The unlabelled compound 2-I-ICI-H showed high beta(1)-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac beta-adrenoceptors. The radiolabelled counterpart 2-(125)I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac beta(1)-adrenoceptors in vivo. CONCLUSION: Because of its high non-specific binding 2-(125)I-ICI-H is no suitable radiotracer for imaging in vivo.

Radioligands for imaging myocardial alpha- and beta-adrenoceptors.

Alpha- and beta-adrenoceptors play an important role in the control of heart function. According to their molecular, biological, and pharmacological characteristics, they are subdivided into alpha(1)-, alpha(2)- and beta(1)-, beta(2)-, beta(3)-, beta(4)-adrenoceptors. In cardiac disease, there is often a selective downregulation of beta(1)-adrenoceptors associated with a relative increase in beta(2)- and alpha(1)-adrenoceptors. Functional imaging techniques like single-photon emission tomography (SPECT) and positron emission tomography (PET) provide the unique capability for non-invasive assessment of cardiac adrenoceptors. Radioligands with high specific binding to cardiac alpha- and beta-adrenoceptors suitable for radiolabelling are required for clinical studies. The non-selective beta-adrenoceptor antagonist [(11)C]CGP-12177 was used to quantify beta-adrenoceptor density using PET in patients with heart disease. New non-selective ligands (e. g. [(11)C]CGP-12388, [(18)F]CGP-12388, [(11)C]carazolol and [(18)F]fluorocarazolol) are currently evaluated; beta(1)-selective radioligands (e. g. [(11)C]CGP-26505, [(11)C]bisoprolol, [(11)C]HX-CH 44) and beta(2)-selective radioligands (e. g. [(11)C]formoterol, [(11)C]ICI-118551) were assessed in animals. None of them turned out as suitable for cardiac PET. Potential radioligands for imaging cardiac alpha(1)-adrenoceptors are based on prazosin. Whereas [(11)C]prazosin shows low specific binding to myocardium, its derivative [(11)C]GB67 looks more promising. The putative alpha(2)-adrenoceptor radioligand [(11)C]MK-912 shows high uptake in rodent myocardium but has not yet been evaluated in man. A number of radioligands were evaluated for assessing cardiac adrenoceptors using PET. New radioligands are needed to provide more insight into cardiac pathophysiology which may influence the therapeutic management of patients with cardiovascular disease.

I-123-lodo-alpha-methyl tyrosine SPECT in non-parenchymal brain tumours.

PURPOSE: Scintigraphy using I-123-iodo-alpha-methyl tyrosine (IMT) is useful in the preoperative characterization of gliomas, in detecting recurrent glioma and in the biological re-evaluation of residual or recurrent tumours. A systematic evaluation of non-parenchymal brain tumours has not yet been performed. The aim of the present study was to evaluate IMT SPECT in the management of intracerebral metastases and lymphomas. PATIENTS AND METHODS: IMT uptake was analyzed in 31 patients with 28 metastases of extracerebral solid tumours and 7 cerebral lymphomas. Histology revealed high grade lymphomas, melanomas, and carcinomas of the following origin: lung, unknown primary, breast, colon, renal cell, ovary, vagina, frontal sinus. IMT uptake was quantified as ratio between maximal tumour accumulation and average uptake in the contralateral hemisphere. RESULTS: All tumours except two renal cell and one small cell lung carcinoma metastases accumulated IMT (91%). The highest IMT uptake was found in a metastasis of lung carcinoma. IMT uptake was highly variable and was similar in primary and in recurrent tumours. CONCLUSION: Significant accumulation of IMT is seen in the majority of tumours, so that this technique might be helpful for the management of cerebral metastases and lymphomas.