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We aimed to assess the value of 11C-choline PET in patients with primary hyperparathyroidism and negative or discordant results on 99mTc-sestamibi imaging and neck ultrasound. Methods: Eighty-seven such patients were assessed and subsequently underwent parathyroidectomy. PET/CT image data were analyzed semiquantitatively using SUVmax and SUV ratios (target to contralateral thyroid gland and carotid artery). A positive PET/CT result was defined as focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT result was considered negative. Results: When dichotomizing the 11C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, we found 84 of 92 lesions (91.3%) to have true-positive uptake whereas 8 lesions (8.7%) had false-positive uptake. One lesion showed false-negative uptake; the sensitivity was 98.8%. The corresponding positive predictive value for lesions was 91.3%. The mean SUVmax was 6.15 ± 4.92 in 72 lesions with positive uptake (70 patients) and 2.96 ± 2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that 11C-choline PET/CT is a promising tool for parathyroid adenoma localization when ultrasound and 99mTc-sestamibi imaging yield negative or discordant results.

Auf dem Boden internationaler Leitlinien der American and British Thyroid Association wird auch beim fortgeschrittenen Radioiodrefraktaren differenzierten Schilddrusenkarzinom (DTC) ein individualisiertes und risikoadaptiertes Vorgehen angestrebt. Der selektive Einsatz der systemischen molekular gezielten Therapie erfolgt erst nach Ausschopfen nebenwirkungsarmerer lokaler palliativer Therapieverfahren und wenn bei hoher Tumorlast und signifikantem Progress eine Watch-and-Wait-Strategie nicht mehr vertretbar ist. Neben den beiden zugelassenen Tyrosinkinaseinhibitoren (TKI) Lenvatinib und Sorafenib stehen eine Reihe weiterer TKI (Cabozantinib, Pazopanib, Sunitinib, Axitinib) sowie selektiver Inhibitoren (Everolimus, Dabrafenib ± Trametinib, Vemurafenib, Tropomyosin-Rezeptor-Kinase(TRK)- und RET-Inhibitoren) im Rahmen von Studien oder im individuellen Heilversuch zur Verfugung zum individualisierten Einsatz unter Berucksichtigung der Patientencharakteristika, einschlieslich Alter, Komorbiditaten, individueller Patientenwunsch sowie Tumorcharakteristika. Von grosem Potenzial ist auch die Moglichkeit der Reetablierung der Radioiodtherapie durch Reinduktion einer Radioiodaufnahme in den Tumor durch BRAF-Inhibition und/oder MEK-Inhibition, was derzeit in mehreren klinischen Studien untersucht wird. Um die molekular gezielten Therapiemoglichkeiten im Rahmen eines individualisierten Therapiekonzepts voll ausschopfen zu konnen, wird heute beim Radioiodrefraktaren DTC eine fruhzeitige molekulargenetische Analyse des Tumorgewebes dringend empfohlen. Um eine optimale individuelle Therapieplanung unter Ausschopfung aller Therapieoptionen, einschlieslich Einschluss in kontrollierte klinische Studien, zu gewahrleisten, sollten Patienten mit fortgschrittenen Radioiodrefraktaren DTC unbedingt von einem interdisziplinaren Expertenteam an spezialisierten Zentren betreut werden.

ZusammenfassungDie Version 5 der Verfahrensanweisung für die Iod-131 Ganzkörperszintigrafie beim differenzierten Schilddrüsenkarzinom ist ein Update der Version 4, publiziert durch die Deutsche Gesellschaft für Nuklearmedizin (DGN). Diese Verfahrensanweisung beschreibt mit primärer Zielsetzung die fachgerechte Durchführung der Ganzkörperszintigrafie nach Applikation einer diagnostischen bzw. einer therapeutischen I-131 Aktivität. Die Verfahrensanweisung wurde von einer repräsentativen Expertengruppe im Konsensverfahren verabschiedet. Sie entspricht damit einer Verfahrensanweisung der ersten Stufe (S1) nach den Kriterien der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF).

ZusammenfassungIn der Nebenniere liegen 2 distinkt unterschiedliche Gewebe, das Nebennierenmark und die Nebennierenrinde vor. Beide Gewebearten sezernieren unterschiedliche Hormone und besitzen eigene molekulare Charakteristika, die für eine spezifische Bildgebung mit Radiotracern genutzt werden können. Für das Nebennierenmark sind dies der Noradrenalin-Re-Uptake-Transporter und, beschränkt, auch der Somatostatinrezeptor. Für die Nebennierenrinde ist eine spezifische Darstellung von Enzymen der Cortisol- und Aldosteronbiosynthese möglich. In theranostischen Ansätzen wurden alle Zielstrukturen bisher bereits für gezielte Radionuklidtherapien genutzt, jedoch ist bisher lediglich die Noradrenalin-Re-Uptake-Transporter-gezielte 131I-metaIodBenzylGuanidin (mIBG)-Behandlung klinisch etabliert.

ZusammenfassungEines der vielversprechendsten Konzepte in der Nuklearmedizin ist die Theranostik, die im Wesentlichen die Diagnostik und Therapie eines bestimmten Targets beinhaltet, insbesondere, wenn es darum geht, Krebstherapien zu optimieren und zu individualisieren. In der Nuklearmedizin werden Theranostika bereits seit über 60 Jahren in der klinischen Routine mit 131J/123J für diagnostische und therapeutische Zwecke bei Schilddrüsenerkrankungen eingesetzt. Dieser Artikel gibt einen kurzen Überblick über die Verwendung von 2 Radioiod-Isotopen (131J und 124J) für das Targeting des Natrium-Iodid-Symporters bei Schilddrüsenkarzinomen und nicht thyreoidalen Tumoren. Insbesondere wird die Rolle der 124J-basierten Dosimetrie diskutiert. Abschließend zeigen wir an einem Patientenbeispiel, wie die Expression des Natrium-Iodid-Symporters bei einem Patienten mit radioiod-refraktärem fortgeschrittenem Schilddrüsenkarzinom durch Medikamente manipuliert werden kann.

Background: The use of 18F-2-Fluor-2-desoxy-D-glucose Positron Emission Tomography/Computed Tomography FDG-PET/CT in clinical routine for staging, treatment response monitoring and post treatment surveillance in metastatic melanoma patients has noticeably increased due to significant improvement of the overall survival rate in melanoma patients. However, determining the dignity of the findings with increased metabolic activity on FDG-PET/CT can be sometimes challenging and may need further investigation. Purpose: We aimed to investigate the malignancy rate of indeterminate findings on FDG-PET/CT in metastatic cutaneous melanoma patients. Methods: This single-center retrospective study included cutaneous melanoma patients who underwent FDG-PET/CT in clinical routine between 2015 and 2017 with findings reported as indeterminate and therefore requiring further evaluation. The dignity of the included findings was determined by subsequent imaging and, if required, additional histopathology. The impact of the outcome on the clinical management was also reported. Results: A total of 842 FDG-PET/CT reports of 244 metastatic cutaneous melanoma patients were reviewed. Sixty indeterminate findings were included. Almost half of all indeterminate findings were lymph nodes, lung nodules and cerebral lesions. In total, 43.3% of all included findings proved to be malignant. 81% of all malignant lesions were metastases of cutaneous melanoma, while 19% of all malignant lesions could be attributed to other primary malignancies, such as lung, breast, thyroid and colorectal cancers. Malignant findings influenced clinical management in 60% of the cases. Conclusion: Indeterminate findings on FDG-PET/CT in metastatic cutaneous melanoma patients should be further investigated. Almost one out of every two indeterminate findings on FDG-PET/CT is malignant. The majority of the findings are melanoma manifestations, however, in a significant percentage, other primary tumors are found. Upon verification, patient management is changed in most cases.

Both, ultrasonography but also radionuclide imaging using [99mTc]Pertechnetate or radioactive iodine isotopes are essential tools used during the diagnostic workup of hyperthyroidism with or without structural alterations of the thyroid. Colour duplex sonography and ultrasound elastography may add important information in order to find the cause of the hormone excess. During the last years, also hybrid imaging using SPECT/-(CT) or PET-based methods, such as [124]Iodine-PET/CT or [124]Iodine-PET/ultrasound also have nodularbeen increasingly used and especially play a role in the context of localizing ectopic thyroid tissue or in multinodular goiter. Recently also promising data has been published on the use of [99mTc]MIBI imaging in amiodarone induced hyperthyroidism.

The authors wish to make the following corrections to this paper [...]

Purpose Molecular imaging with 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI, MIBI) has been used in the assessment of thyroid nodules (TNs) for more than two decades. Many studies showed that MIBI imaging is a suitable tool to rule-out malignancy when negative. However, relatively low specificity and accuracy have been described, thus, limiting its acceptance in clinical practice. Additionally, different technologies, protocols, and interpretation criteria are adopted accounting for heterogeneous data reported in the literature. Therefore, the present study was undertaken to assess the clinical use and methodology of MIBI imaging in patients with nodular thyroid disease in Europe. Methods A questionnaire was sent to 12 European centers of Nuclear Medicine. The questionnaire encompassed ultrasound (US) and fine-needle aspiration cytology (FNAC) procedures and their evaluation as well scintigraphy imaging indications, technical procedures, and interpretation criteria of MIBI imaging. Results The survey showed a good agreement of different centers in approaching TNs by TSH measurement, US evaluation and 99mTc-pertechnetate thyroid scintigraphy. MIBI imaging is mainly used to assess TNs with inconclusive/indeterminate cytological findings and selection of target nodule(s) for FNAC in patients with multi-nodular goiter. Technical procedures adopted in different centers are globally comparable and the recorded differences are unlikely to impact clinical results. However, as the main result of the present study, substantial differences were found in interpretation criteria adopted in different centers. Conclusions Our survey supports the urgent need of standardized interpretation criteria of thyroid MIBI imaging in order to improve its diagnostic performance and make results comparable in clinical practice.

BACKGROUND Literature reporting [18F]fluorodexoyglucose positron emission tomography (FDG-PET) of small bowel adenocarcinoma, a rare tumor, is sparse. To assess FDG uptake in small bowel adenocarcinoma, we retrospectively analyzed a large, single-center database and determined the expression of glucose-transporter type 1 (GLUT-1). METHODS Screening of PET datasets in the database (N.=28,961 scans) for untreated histologically-confirmed primary small bowel adenocarcinoma revealed evaluable PET datasets for eight patients. Maximum and peak standardized uptake values (SUV max and SUV peak , respectively) were calculated via volume-of-interest (VOI) analysis. Additionally, GLUT-1 expression on tumor specimens was prospectively immunohistochemically assessed. RESULTS All primary tumors showed high FDG uptake: mean SUVmax was 9.5±2.6 (range: 5.0-13.0) and SUVpeak, 8.1±2.3 (range: 3.9-10.7). Corresponding biopsy specimens (N.=7) demonstrated high GLUT-1 expression. CONCLUSIONS Primary small bowel adenocarcinomas have a high GLUT-1 expression. Tumor lesions consistently demonstrated high FDG uptake pre-treatment, suggesting FDG-PET utility in staging and follow-up of these tumors.

The bone scan index (BSI), initially introduced for metastatic prostate cancer, quantifies the osseous tumor load from planar bone scans. Following the basic idea of radiomics, this method incorporates specific deep-learning techniques (artificial neural network) in its development to provide automatic calculation, feature extraction, and diagnostic support. As its performance in tumor entities, not including prostate cancer, remains unclear, our aim was to obtain more data about this aspect. The results of BSI evaluation of bone scans from 951 consecutive patients with different tumors were retrospectively compared to clinical reports (bone metastases, yes/no). Statistical analysis included entity-specific receiver operating characteristics to determine optimized BSI cut-off values. In addition to prostate cancer (cut-off = 0.27%, sensitivity (SN) = 87%, specificity (SP) = 99%), the algorithm used provided comparable results for breast cancer (cut-off 0.18%, SN = 83%, SP = 87%) and colorectal cancer (cut-off = 0.10%, SN = 100%, SP = 90%). Worse performance was observed for lung cancer (cut-off = 0.06%, SN = 63%, SP = 70%) and renal cell carcinoma (cut-off = 0.30%, SN = 75%, SP = 84%). The algorithm did not perform satisfactorily in melanoma (SN = 60%). For most entities, a high negative predictive value (NPV ≥ 87.5%, melanoma 80%) was determined, whereas positive predictive value (PPV) was clinically not applicable. Automatically determined BSI showed good sensitivity and specificity in prostate cancer and various other entities. Particularly, the high NPV encourages applying BSI as a tool for computer-aided diagnostic in various tumor entities.

PURPOSE We conducted a post hoc analysis of the vandetanib phase III trial involving patients with advanced medullary thyroid cancer (MTC) to assess the efficacy and safety of vandetanib in patients with progressive and symptomatic MTC. The primary objective of the analysis was to determine progression-free survival (PFS) of these patients. PATIENTS AND METHODS Eligible patients from the ZETA trial were divided into 4 disease severity subgroups: progression and symptoms, symptoms only, progression only, and no progression and no symptoms assessed at baseline. PFS, determined from objective tumor measurements performed by the local investigator, overall survival (OS), time to worsening of pain (TWP), and objective response rate (ORR) were evaluated. RESULTS Of the 331 patients in this trial, 184 had symptomatic and progressive disease at baseline. In this subgroup, results were similar in magnitude to those observed in the overall trial for PFS (hazard ratio [HR], 0.43; 95% CI, 0.28 to 0.64; P < .0001), OS (HR, 1.08; 95% CI, 0.72 to 1.61; P = .71), and TWP (HR, 0.67; 95% CI, 0.43 to 1.04; P = .07), and the observed adverse events were consistent with the known safety profile of vandetanib. In this subgroup, the ORR was 37% in the treatment arm versus 2% in the placebo arm. CONCLUSION Vandetanib demonstrated clinical benefit—specifically, increased PFS—in patients with symptomatic and progressive MTC.

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is routinely used in diffuse large B cell lymphoma (DLBCL) for staging, assessment of remission and recurrence, and estimation of therapeutic efficacy. In this study, we aimed to assess the role of an early interim PET/computed tomography (CT) in the evaluation of response in DLBCL. Sixty primary DLBCL patients (31 females) were analyzed. Baseline and follow-up 18F-FDG PET/CT was performed in patients after one cycle (n = 30) and two cycles (n = 30) of chemotherapy. The ΔSUVmax% was calculated. Patients were additionally evaluated using the conventional Deauville five-point scale (D-5PS) system. Fluorescence in situ hybridization (FISH) was employed to characterize the MYC gene status. We determined the optimum cutoff value of ΔSUVmax% using receiver operating characteristic (ROC) analysis. Kaplan–Meier analysis was applied to test for the influence of prognostic values. The optimal cutoff for the prediction of treatment outcome was a ΔSUVmax% of 57% (after one cycle) and 63% (after two cycles); we could not detect a difference in accuracy with respect to a PET scan performed after one cycle and two cycles of chemotherapy (P > 0.05). The ΔSUVmax% and the D-5PS (score 5) showed the highest prognostic value compared to a score of 3 and/or 4 (both after one cycle and two cycles). No significant difference in sensitivity, specificity, accuracy, or the area of under the curve (AUC) of ΔSUVmax% and D-5PS (score 5) was observed between PETs performed after one cycle or two cycles of therapy (P > 0.05). ΔSUVmax%, D-5PS (score 5), and MYC gene rearrangement correlated significantly (P

Lenvatinib has been approved for the treatment of advanced differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) following the results of the SELECT trial which demonstrated a significant increase in progression-free survival and a high response rates. The data reported for lenvatinib in RAI-refractory DTC (RAI-R DTC) are the most significant to date in this patient population, with a RECIST objective response rate above 60% and almost 80% reduction in the risk of disease progression. Because the first indication in oncology for lenvatinib is specifically in RAI-R DTC, a period of familiarisation with its safety and efficacy profile is required. This review includes a series of specific recommendations for optimising the management of RAI-R DTC with lenvatinib, as well as specific guidelines for minimising the incidence and severity of adverse events (AEs), which enable dose intensity to be increased and this way maximise the benefits of the drug in the patient population treated. These recommendations were defined at a meeting of experts of different specialities, reviewing available scientific evidence on the drug, as well as their own direct personal experience in daily clinical practice. For toxicity to be properly managed, a multidisciplinary approach is required in which the different medical services, nursing staff and the patient and their careers are all involved. It is essential to assess the suitability of patients who are candidates for lenvatinib, as well as their clinical and physiological status prior to treatment. They must then be closely monitored to prevent and detect possible AEs. The main objective should be to maintain the dose that obtains the maximum therapeutic effect, discontinuing the treatment only if the toxicity becomes unmanageable or there is no clinical benefit.

Summary Objectives: Low-dose-computed tomography (LD-CT) is used in nuclear medicine hybrid imaging (e.g., SPECT/CT) for attenuation correction of emission data and anatomical correlation of findings. However, there are currently no standards for image quality (e. g., detectability) comparable to those for diagnostic CT. Therefore, the aim of this explorative study was to evaluate retrospective LDCT data in terms of CT image quality and detectability of anatomical structures. Methods: Two readers blindly scored abdominal LD-CT images (n = 40 patients) in terms of detectability (n = 20 structures/patient), image quality, and readers’ confidence in scoring the image quality for a clinically hybrid imaging protocol. Results were analysed by ANOVA to identify factors (e. g., anatomical structures) that influenced performance scores. The inter-rater agreement was evaluated by determining the chance-corrected Cohen’s Kappa coefficient. Results: Image noise was acceptable for anatomical correlation in 96.1 % of the readings with an almost perfect inter-rater agreement (KBP = 0.85). A detectability of at least 80 % was observed in 13/20 (KBP ≥ 0.7) and 90 % in 9/20 (KBP ≥ 0.85) of the structures analysed by both readers. The confidence of both readers in scoring image quality was at least sufficient in 98.8 % of the examined patients (KBP = 0.95). Conclusion: Although LD-CT protocols commonly used in hybrid imaging have a poor image quality not suitable for primary CT diagnostics, they enable detection of a variety of anatomical structures. LDCT can therefore also be referenced in the associated reports for anatomical correlation of findings from SPECT imaging.

ZusammenfassungFür die Berechnung der Therapieaktivität im Rahmen der Selektiven Internen Radiotherapie (SIRT oder auch Radioembolisation) existieren unterschiedlich elaborierte Berechnungsmodelle. Diese besitzen empirischen Charakter bzw. basieren auf makroskopischen Ansätzen unter der Annahme einer Gleichverteilung der Mikrosphären und damit der akkumulierten Dosis (MIRD-basierter Modellansatz). Eine Inhomogenität in der Anreicherung des Radioembolisats, welche regulär durch die post-therapeutische Bildgebung beobachtet wird, findet in den Dosierungskonzepten keine Berücksichtigung. Für die weitere Entwicklung wäre es hier wünschenswert, radiobiologische Konzepte stärker zu integrieren und eine Dosierung der Therapieaktivität unter Berücksichtigung der (limitierenden) gewebsspezifischen Toleranzen durchzuführen.Generell sind die Bewertung der Effektivität und der Nebenwirkungen sowie die damit verbundene Definition von Toleranzdosen/Zieldosen schwierig. Die verfügbaren Daten weisen aufgrund der Heterogenität der untersuchten Endpunkte, unterschiedlicher basaler Leberfunktion und individueller Erkrankungshistorien (Vortherapie) eine große Streuung und eine damit verbundene große Unsicherheit auf.

Due to the widespread use of ultrasound, small thyroid nodules (TNs) &le, 10 mm are common findings. Standardized approaches for the risk stratification of TNs with Thyroid Imaging Reporting and Data Systems (TIRADS) were evaluated for the clinical routine. With TIRADS, the risk of malignancy in TNs is calculated by scoring the number or combination of suspicious ultrasound features, leading to recommendations for further diagnostic steps. However, there are only scarce data on the performance of TIRADS for small TNs. The aim was to compare three different TIRADS for risk stratification of small TNs in routine clinical practice. We conducted a retrospective cohort analysis of TNs &le, 10 mm and their available histology. Nodules were classified according to three different TIRADS. In the study, 140 patients (n = 113 female) with 145 thyroid nodules (n = 76 malignant) were included. Most of the malignant nodules were papillary carcinoma (97%), and the remaining 3% were medullary carcinoma. For all tested TIRADS, the prevalence of malignancy rose with increasing category levels. The highest negative predictive value was found for ACR TI-RADS and the highest positive predictive value for Kwak-TIRADS. All tested variants of TIRADS showed comparable diagnostic performance for the risk stratification of small TNs. TIRADS seems to be a promising tool to reliably assess the risk of malignancy of small TNs.

It is challenging to differentiate unilateral aldosterone-producing adenoma (APA) from bilateral idiopathic adrenal hyperplasia (IAH) and nonfunctional adrenal adenoma (NFA) in primary aldosteronism (PA). In a first primarily ex vivo study detection, CXC chemokine receptor type 4 (CXCR4) expression has been shown to be a valuable tool for the detection of APA. In this study, we aimed to clinically evaluate CXCR4 imaging with 68Ga-pentixafor PET/CT for detecting APA. We prospectively recruited 36 patients with clinical suspicion of PA. All patients underwent 68Ga-pentixafor PET/CT. Positive lesions were defined based on higher tracer uptake in adrenal nodular(s) shown on CT than the normal adrenal. These lesions were referred for adrenalectomy subsequently. All patients received clinical follow-up. Semi-quantitative analysis using maximum standardized uptake value (SUVmax), lesion-to-liver ratio (LLR), and lesion-to-contralateral ratio (LCR) has also been performed. PET/CT results were correlated with clinical presentation and follow-up. Thirty-nine adrenal lesions in 36 patients were found; 25 APA, 4 IAH, and 10 NFA according to histopathology and clinical assessment. Sensitivity, specificity, and accuracy of 68Ga-pentixafor PET/CT in distinguishing APA by visualization were 100%, 78.6%, and 92.3% respectively. The SUVmax of APA (21.34 ± 9.41, n = 25) was significantly higher than that of non-APA lesions (6.29 ± 2.10, n = 14, P

To evaluate the diagnostic value ofWe analyzed 38 patients with cardiac tumors who underwentOptimal cut-off values indicating malignancy were as follows: SUV

Background Radiation therapy using beta particles is an interesting treatment for very superficial skin lesions. Due to their low penetration in tissue and rapid dose fall-off, beta particles can protect underlying bony structures and surrounding healthy tissue while irradiating the skin tumor. In the current work, a simple method for the fabrication of a radioactive patch for use in skin cancer therapy based on a beta-emitting isotope is presented. Materials and methods The beta radiation sources were Y-90 microspheres currently used for catheter-based radioembolization of unresectable liver tumors. The microspheres were filtered through a syringe filter to trap them on the cellulose nitrate paper of the filter and create a radioactive patch. In the current study, to avoid the need for a hot laboratory, the experiment was done using nonradioactive microspheres. An optical microscope was used to verify the distribution of the particles on the filter paper. Results Visual evaluation of the patches showed that using the proposed method, therapeutic skin patches with a fairly uniform distribution of microspheres can be created. Conclusion The proposed simple method may be used in creating radiotherapeutic patches using Y-90 microspheres for radiation therapy of thin skin lesions located close to sensitive structures.

Background Iterative computed tomography (CT) image reconstruction shows high potential for the preservation of image quality in diagnostic CT while reducing patients’ exposure; it has become available for low-dose CT (LD-CT) in high-end hybrid imaging systems (e.g. single-photon emission computed tomography [SPECT]-CT). Purpose To examine the effect of an iterative CT reconstruction algorithm on image quality, image noise, detectability, and the reader’s confidence for LD-CT data by a subjective assessment. Material and Methods The LD-CT data were validated for 40 patients examined by an abdominal hybrid SPECT-CT (U = 120 kV, I = 40 mA, pitch = 1.375). LD-CT was reconstructed using either filtered back projection (FBP) or an iterative image reconstruction algorithm (Adaptive Statistical Iterative Reconstruction [ASIR]®) with different parameters (ASIR levels 50% and 100%). The data were validated by two independent blinded readers using a scoring system for image quality, image noise, detectability, and reader confidence, for a predefined set of 16 anatomic substructures. Results The image quality was significantly improved by iterative reconstruction of the LD-CT data compared with FBP ( P ≤ 0.0001). While detectability increased in only 2/16 structures ( P ≤ 0.03), the reader’s confidence increased significantly due to iterative reconstruction ( P ≤ 0.002). Meanwhile, at the ASIR level of 100%, the detectability in bone structure was highly reduced ( P = 0.003). Conclusion An ASIR level of 50% represents a good compromise in abdominal LD-CT image reconstruction. The specific ASIR level improved image quality (reduced image noise) and reader confidence, while preserving detectability of bone structure.

Thyroid scintigraphy with Retrospective analysis of planar and SPECT images of MIBI scintigraphy was performed in 36 randomly selected patients with hypofunctioning TN and histological diagnosis. Four observers with different levels of experience in MIBI-scintigraphy analyzed MIBI uptake and assigned the nodules to the appropriate category. To assess the IA, Fleiss' Kappa was calculated. The study cohort included 11 patients with papillary thyroid carcinoma (diameter 20.3 mm) and 25 patients with benign nodules (diameter 24.8 mm). The IA for all nodules using planar images was 0.76 compared to 0.80 for SPECT images. The IA was better in the subgroup of malignant nodules for planar images as well as SPECT images (Kappa 0.91 and 0.90, respectively) compared to benign nodules (0.65 and 0.76, respectively). Using SPECT images, only one thyroid carcinoma presented with hypointense uptake, the remainder with hyper- or isointense uptake. In contrast, benign nodules were found in all categories. MIBI scintigraphy shows a good IA for the interpretation of thyroid carcinoma. The IA is further improved if MIBI scintigraphy is performed in SPECT technique. Die Szintigraphie mit Retrospektive Analyse der planaren Bilddaten und der SPECT-Aufnahmen der MIBI-Untersuchungen von 36 randomisierten Patienten mit mindestens einem hypofunktionellen Knoten und vorliegender Histologie. Vier Untersucher (Erfahrungslevel: drei mit 2 und einer mit 4 Jahren) beurteilten die Knoten hinsichtlich des MIBI-Speichermusters: hypo-, iso- und hyperintens. Zur Beurteilung des Interobserver-Agreements wurde das Fleiss‘ Kappa berechnet. Es wurden 11 papilläre Karzinome (20,3 mm) und 25 benigne Knoten (24,8 mm) beurteilt. Der Übereinstimmungswert (Kappa-Wert) für das Gesamtkollektiv lag für die planaren Bilder bei 0,76, für die SPECT-Bilder bei 0,80. Werden nur die Karzinome betrachtet, lag das Kappa höher (planar 0,91; SPECT 0,90) als bei den benignen Knoten (planar 0,65; SPECT 0,76). Während nur ein Karzinom im SPECT als hypointens beurteilt wurde, zeigten die übrigen ein iso- und hyperintenses Muster. Die benignen Knoten verteilten sich über allen drei Kategorien. Die MIBI-Szintigraphie zeigt insbesondere bei der Beurteilung von Schilddrüsenkarzinomen eine gute Übereinstimmung, die durch SPECT noch verbessert werden kann.

Version 5 of the procedural guideline for Iodine-131 whole-body scintigraphy (WBS) in differentiated thyroid carcinoma is an update of the version 4, published by the "Deutsche Gesellschaft für Nuklearmedizin" (DGN). This procedural guideline advises on how to best perform I-131 whole body scintigraphy after I-131 therapy or after application of a diagnostic I-131 activity. A representative expert group has discussed and reached consensus on the procedural guideline; the development of this procedural guideline therefore fulfils the criteria for level S1 (first step) within the classification of the German Workgroup of Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften"; AWMF).Die Version 5 der Verfahrensanweisung für die Iod-131 Ganzkörperszintigrafie beim differenzierten Schilddrüsenkarzinom ist ein Update der Version 4, publiziert durch die Deutsche Gesellschaft für Nuklearmedizin (DGN). Diese Verfahrensanweisung beschreibt mit primärer Zielsetzung die fachgerechte Durchführung der Ganzkörperszintigrafie nach Applikation einer diagnostischen bzw. einer therapeutischen I-131 Aktivität. Die Verfahrensanweisung wurde von einer repräsentativen Expertengruppe im Konsensverfahren verabschiedet. Sie entspricht damit einer Verfahrensanweisung der ersten Stufe (S1) nach den Kriterien der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF).

Context Anaplastic thyroid carcinoma (ATC) is an orphan disease and confers a dismal prognosis. Standard treatment is not established. Objective The aim of this study is to describe clinical characteristics, current treatment regimens and outcome of ATC and to identify clinical prognostic markers and treatment factors associated with improved prognosis. Design Retrospective cohort study at five German tertiary care centers. Patients and methods Totally 100 ATC patients diagnosed between 2000 and 2015 were included in the analysis. Disease-specific overall survival (OS) was compared with the Kaplan–Meier method and log-rank test; Cox proportional hazard model was used to identify risk factors. Results The 6-month, 1-year and 5-year disease-specific OS rates were 37, 28 and 5%, respectively. Stage-dependent OS at 6 months was 78, 54 and 18% for stage IVA, B and C, respectively. 29% patients survived >1 year. Multivariate analysis of OS identified age ≥70 years, incomplete local resection status and the presence of distant metastasis as significant risk factors associated with shorter survival. Radical surgery (hazard ratio [HR] 2.20, 95% confidence interval (CI) 1.19–4.09, P = 0.012), external beam radiation therapy (EBRT) ≥40 Gy (HR = 0.34, 0.15–0.76, P = 0.008) and any kind of chemotherapy (CTX) (HR = 11.64, 2.42–60.39, P = 0.003) were associated with longer survival in multivariate analyses adjusted for age and tumor stage. A multimodal treatment regimen was significantly associated with a survival benefit (HR = 1.04, 1.01–1.08, P Conclusion Disease-specific OS is still poor in ATC. Treatment factors associated with improved OS provide a rationale to devise treatment pathways for routine care. Collaborative research structures should be aimed to advance treatment of ATC.

On successful completion of this activity one should be able to judge the prognosis of patients harboring metastasized differentiated thyroid cancer (DTC); identify suitable treatment regimens, taking into account the characteristics of the tumor and the patient's general condition; and know the basics of radioiodine treatment, tyrosine kinase treatment, and redifferentiation treatment for metastasized DTC.

Objectives 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is routinely used in diffuse large B cell lymphoma (DLBCL) for staging, assessment of remission and recurrence, and estimation of therapeutic efficacy. In this study, we aimed to assess the role of an early interim PET/computed tomography (CT) in the evaluation of response in DLBCL. Methods Sixty primary DLBCL patients (31 females) were analyzed. Baseline and follow-up 18F-FDG PET/CT was performed in patients after one cycle (n = 30) and two cycles (n = 30) of chemotherapy. The ΔSUVmax% was calculated. Patients were additionally evaluated using the conventional Deauville five-point scale (D-5PS) system. Fluorescence in situ hybridization (FISH) was employed to characterize the MYC gene status. We determined the optimum cutoff value of ΔSUVmax% using receiver operating characteristic (ROC) analysis. Kaplan–Meier analysis was applied to test for the influence of prognostic values. Results The optimal cutoff for the prediction of treatment outcome was a ΔSUVmax% of 57% (after one cycle) and 63% (after two cycles); we could not detect a difference in accuracy with respect to a PET scan performed after one cycle and two cycles of chemotherapy (P > 0.05). The ΔSUVmax% and the D-5PS (score 5) showed the highest prognostic value compared to a score of 3 and/or 4 (both after one cycle and two cycles). No significant difference in sensitivity, specificity, accuracy, or the area of under the curve (AUC) of ΔSUVmax% and D-5PS (score 5) was observed between PETs performed after one cycle or two cycles of therapy (P > 0.05). ΔSUVmax%, D-5PS (score 5), and MYC gene rearrangement correlated significantly (P

Purpose The metabolically most active lesion in 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic 18F-FDG PET. Methods Eighteen patients with progressive MTC underwent baseline 18F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated. Results The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3 y (vs. low-risk group, OS = 5.3 y, 8/18, AUC = 0.78, P = 0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS = 3.5 y vs. low-risk group, OS = 5 y, 7/18, AUC = 0.83, P = 0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P = 0.02, OS, n.s.). Conclusions The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.

Hyperinsulinemia is thought to enhance cancer risk. A possible mechanism is induction of oxidative stress and DNA damage by insulin, Here, the effect of a combination of metformin with insulin was investigated in vitro and in vivo. The rationales for this were the reported antioxidative properties of metformin and the aim to gain further insights into the mechanisms responsible for protecting the genome from insulin-mediated oxidative stress and damage. The comet assay, a micronucleus frequency test, and a mammalian gene mutation assay were used to evaluate the DNA damage produced by insulin alone or in combination with metformin. For analysis of antioxidant activity, oxidative stress, and mitochondrial disturbances, the cell-free ferric reducing antioxidant power assay, the superoxide-sensitive dye dihydroethidium, and the mitochondrial membrane potential-sensitive dye 5,5',6,6'tetrachloro-1,1',3,3'-tetraethylbenzimidazol-carbocyanine iodide were applied. Accumulation of p53 and pAKT were analyzed. As an in vivo model, hyperinsulinemic Zucker diabetic fatty rats, additionally exposed to insulin during a hyperinsulinemic-euglycemic clamp, were treated with metformin. In the rat kidney samples, dihydroethidium staining, p53 and pAKT analysis, and quantification of the oxidized DNA base 8-oxo-7,8-dihydro-2'-deoxyguanosine were performed. Metformin did not show intrinsic antioxidant activity in the cell-free assay, but protected cultured cells from insulin-mediated oxidative stress, DNA damage, and mutation. Treatment of the rats with metformin protected their kidneys from oxidative stress and genomic damage induced by hyperinsulinemia. Metformin may protect patients from genomic damage induced by elevated insulin levels. This may support efforts to reduce the elevated cancer risk that is associated with hyperinsulinemia.

Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET. Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated. Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.). Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.

ZusammenfassungIn den vergangenen Jahren wurden drei neue Substanzen für die molekular gezielte Therapie des fortgeschrittenen und progredienten Schilddrüsenkarzinoms zugelassen: Vandetanib und Cabozantinib für das medulläre Schilddrüsenkarzinom sowie Sorafenib für das Radioiod-refraktäre differenzierte Schilddrüsenkarzinom. Die Selektion der Patienten durch ein interdisziplinäres Team sowie die Aufklärung der Patienten spielt eine wesentliche Rolle, wenn diese Behandlung in Betracht gezogen bzw. begonnen wird. Nur Patienten mit hoher Tumorlast und/oder symptomatischer bzw. progredienter Erkrankung, die lokalen Therapien nicht zugänglich ist, sollten behandelt werden. Um eine gute Lebensqualität zu erhalten, ist das Management der unerwünschten Arzneimittelwirkungen von größter Bedeutung. Aufgrund der Wirkweise der Tyrosinkinasehemmer ist der Verlauf der Tumormarker Calcitonin und Thyreoglobulin nur bedingt zur Beurteilung des Therapieansprechens und zum Follow-up geeignet, deshalb kommt der morphologischen und metabolischen Bildgebung besondere Bedeutung zu. Ein umschriebener oder geringer Progress sollte nicht unbedingt die Beendigung der Behandlung oder eine Therapieumstellung nach sich ziehen. In der nahen Zukunft werden weitere Substanzen verfügbar sein.

ZusammenfassungIn den vergangenen Jahren wurden drei neue Substanzen für die molekular gezielte Therapie des fortgeschrittenen und progredienten Schilddrüsenkarzinoms zugelassen: Vandetanib und Cabozantinib für das medulläre Schilddrüsenkarzinom sowie Sorafenib für das Radioiod-refraktäre differenzierte Schilddrüsenkarzinom. Die Selektion der Patienten durch ein interdisziplinäres Team sowie die Aufklärung der Patienten spielt eine wesentliche Rolle, wenn diese Behandlung in Betracht gezogen bzw. begonnen wird. Nur Patienten mit hoher Tumorlast und/oder symptomatischer bzw. progredienter Erkrankung, die lokalen Therapien nicht zugänglich ist, sollten behandelt werden. Um eine gute Lebensqualität zu erhalten, ist das Management der unerwünschten Arzneimittelwirkungen von größter Bedeutung. Aufgrund der Wirkweise der Tyrosinkinasehemmer ist der Verlauf der Tumormarker Calcitonin und Thyreoglobulin nur bedingt zur Beurteilung des Therapieansprechens und zum Follow-up geeignet, deshalb kommt der morphologischen und metabolischen Bildgebung besondere Bedeutung zu. Ein umschriebener oder geringer Progress sollte nicht unbedingt die Beendigung der Behandlung oder eine Therapieumstellung nach sich ziehen. In der nahen Zukunft werden weitere Substanzen verfügbar sein.Nachdruck aus und zu zitieren als: Nuklearmedizin 2015; 54: 88–93

Background Primary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up. Patients and methods EXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomized (2:1) to cabozantinib (140 mg/day) or placebo. Final OS and updated safety data are reported. Results Minimum follow-up was 42 months. Kaplan-Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 versus 21.1 months) although the difference did not reach statistical significance [stratified hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.64-1.12; P = 0.24]. In an exploratory assessment of OS, progression-free survival, and objective response rate, cabozantinib appeared to have a larger treatment effect in patients with RET M918T mutation-positive tumors compared with patients not harboring this mutation. For patients with RET M918T-positive disease, median OS was 44.3 months for cabozantinib versus 18.9 months for placebo [HR, 0.60; 95% CI, 0.38-0.94; P = 0.03 (not adjusted for multiple subgroup analyses)], with corresponding values of 20.2 versus 21.5 months (HR, 1.12; 95% CI, 0.70-1.82; P = 0.63) in the RET M918T-negative subgroup. Median treatment duration was 10.8 months with cabozantinib and 3.4 months with placebo. The safety profile for cabozantinib remained consistent with that of the primary analysis. Conclusion The secondary end point was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically nonsignificant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest that patients with RET M918T-positive tumors may experience a greater treatment benefit with cabozantinib. Trial registration number NCT00704730.

Rationale Pre-operative lobar function is estimated by scintigraphy in patients with pulmonary malignancies and compromised function. This study compared the lobar perfusion determined by scintigraphy (PS) with data from SPECT/low-dose-CT (SPECT/ldCT) analyzed manually and semi-automatic. Methods Retrospective analysis on 39 patients (m/f = 25/14; age: 72.5 [22–89] years) with indication for pulmonary perfusion scintigraphy. Imaging was performed using SPECT/ldCT. Data was analyzed manually and by semi-automatic software. Readers’ confidence in 3D-segmentation was scored by two independent readers. Interrater agreement was calculated. In addition, Spearman’s rank correlation and Wilcoxon’s test were used. Results Results from PS differed significantly from SPECT/ldCT processed manually or semi-automatically in 4/5 lobes (total difference ≤21.6%; rho ≥0.44) and in 3/5 (total difference 21.6%; rho ≥0.37), respectively. Readers’ confidence in 3D-segmentation showed a perfect interrater agreement (κ = 0.98). Conclusion Quantification of lobar perfusion by SPECT/ldCT differs significantly from planar scintigraphy (e.g., with potential influence on therapy). The semi-automatic software analysis provides an applicable methodology.

Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKIs). We aimed to assess the role of metabolic imaging using

Several studies substantiate the cardioprotective effects of erythropoietin (EPO). Our goal was to quantify the effects of EPO treatment on the early expression of the apoptosis marker phosphatidylserine as well as on the left ventricular volumes and function by means of small animal PET. Myocardial infarction (MI) was induced in C57BL/6 mice. Animals were assigned to saline or EPO groups and underwent Annexin PET (day 2) and gated FDG PET (days 6 and 30). Annexin uptake was significantly higher in the infarction than in remote myocardium, with no differences between treatment groups. Infarct size showed a slight decrease in the EPO group and a slight increase in the controls, which did not reach statistical significance. Follow-up analyses revealed a significant increase of end-diastolic and end-systolic volumes in the EPO group, in which a stable left ventricular ejection fraction (LVEF) was maintained. We find that deleterious effects of EPO can outweigh cardioprotective effects. The present EPO treatment did not significantly reduce apoptosis after MI, but seemingly provoked significant myocardial dilation while maintaining a stable LVEF. Molecular mechanisms of EPO treatment may need further elucidation to optimize therapy regimens.

Das medullare Schilddrusenkarzinom (MTC) ist ein langsam wachsender differenzierter neuroendokriner Tumor mit guter Prognose und Lebensqualitat, der durch Operation geheilt werden kann. Patienten mit postoperativ nur leicht erhohtem Calcitonin (Ct) und geringer Tumorlast zeigen oft einen stabilen asymptomatischen Verlauf. Bei einem kleinen Teil der Patienten ist eine rasche Progression zu beobachten. Zur Therapie des fortgeschrittenen, progredienten metastasierenden MTC stehen jetzt Tyrosinkinaseinhibitoren (TKI) zur Verfugung Die Bedeutung und der Stellenwert der neuen TKI-Therapie im Langzeitverlauf von Patienten mit progredientem metastasierendem MTC werden dargestellt. Indikation und alternative Therapie werden anhand aktueller Studien und Leitlinien diskutiert. Als wichtiger Parameter zur Indikation fur TKI bei progredientem Verlauf haben sich die verkurzte Ct-/CEA-Verdopplungszeit und die durch wiederholte Bildgebung gewonnenen RECIST-Kriterien (RECIST: Response Evaluation Criteria in Solid Tumor) bewahrt. Unter Vandetanib und Cabozantinib kommt es zu einer Verlangerung des progressionsfreien Uberlebens sowie Stabilisierung oder Ruckgang der Tumormasse bei tolerablen Nebenwirkungen. Bei starkeren Nebenwirkungen und/oder Einschrankung der Lebensqualitat ist eine Dosisreduktion oder Therapiepause notwendig. TKI sind eine gute Therapieoption fur das progredient metastasierende MTC, allerdings ergeben sich einige ungeloste Probleme: Dauerbehandlung oder intermittierende Therapie, Kombinationstheapie, Second-Line-Therapie nach Therapieversagen, fruherer Therapiebeginn?

Background: Medullary thyroid cancer (MTC) is a rare tumor entity. The contents of best supportive care (BSC) have not been defined in advanced MTC. The objective of this work is to describe the epidemiology, the treatment patterns with respect to symptom management, as well as palliative treatment and associated costs. Method: A Delphi panel with 9 clinical experts experienced in treating MTC was conducted to obtain details on the epidemiology of MTC and to gain insights into the therapeutic options considered for BSC in advanced MTC in Germany. Unit costs were applied to the described resources from the perspective of the German National Healthcare System in 2011. Results: The annual incidence of MTC in Germany was estimated at about 220. 32% of all patients were estimated to have aggressive/symptomatic MTC, with an estimated mean survival of 36.7 months (median: 36 months). The core element of BSC is relief of symptoms to maintain quality of life. The total mean cost of BSC per patient/year was estimated at € 9,248, lifetime cost at € 28,283. Conclusion: There was consistent agreement within the panel on the epidemiology of MTC and on the structure of the provided therapeutic measures for BSC in advanced MTC, also defining the management of symptoms as a crucial goal of treatment.

Background The rupture of atherosclerotic plaques is triggered by inflammation. Specific detection of inflammation is therefore the focus of many investigations. Noninvasive imaging methods, such as positron emission tomography (PET), also are suited for this purpose. 68 Ga-DOTATATE is a 68 Ga-labeled radiotracer with specific affinity to somatostatin receptor subtype-2 (SSTR-2). SSTR-2 was found specifically expressed on human macrophages/monocytes. Objective We aimed to confirm the distribution of SSTR-2 in inflammatory plaques, and to assess its co-localization with macrophages within the plaques. We also assessed 68 Ga-DOTATATE uptakes in plaques by autoradiography. Method Apolipoprotein E (ApoE)−/− mice on a high-cholesterol diet were injected with 68 Ga-DOTATATE. The animals were sacrificed and aorta sections were examined using autoradiography and immunohistochemistry. Furthermore, expression of SSTR-2 was analyzed by flow cytometry. Western blot was conducted to assess SSTR-2 regulation in basal and lipopolysaccharide (LPS)-activated state. To evaluate the specificity of the 68 Ga-DOTATATE, the sections were pre-incubated with monoclonal SSTR-2 antibody before autoradiography. Result Autoradiographic imaging showed uptake of 68 Ga-DOTATATE co-localized with the macrophage-rich plaques by immunohistochemical examination. A high expression of SSTR-2 on macrophages was found by flow cytometry and western blot. Stimulation with lipopolysaccharide did not alter expression of SSTR-2 in macrophages. Conclusion Due to its specific binding to macrophages, 68 Ga-DOTATATE might be a suitable radiotracer for the evaluation of inflammatory activity in unstable plaques.

Context: Imaging with [123I]iodometomidate ([123I]IMTO) has been shown to diagnose adrenocortical lesions with high sensitivity and specificity. Objective: Our objective was to evaluate the clinical utility of [123I]IMTO imaging in adrenocortical carcinoma (ACC). Design: We conducted a prospective monocentric diagnostic study and a prospective case series at a single tertiary referral center. Patients and Interventions: Fifty-eight patients with histologically confirmed ACC, all European Network for the Study of Adrenal Tumors stage IV (with distant metastases), received 185 MBq [123I]IMTO. Sequential planar whole-body scans until 24 hours post injection and single photon emission computed tomography/computed tomography (SPECT/CT) hybrid imaging 4 to 6 hours post injection were performed. Main Outcome Measures: Outcome measures included uptake of [123I]IMTO in ACC lesions, sensitivity and specificity of [123I]IMTO imaging compared with conventional imaging, and number of patients eligible for [131I]IMTO t...

Adrenal tumors are highly prevalent and represent a wide range of different pathological entities. Conventional imaging often provides only limited information on the origin of these lesions. Novel specific imaging methods are, therefore, of great clinical interest.We evaluated [(123)I]iodometomidate ([(123)I]IMTO) imaging for noninvasive characterization of adrenal masses.This was a prospective monocentric diagnostic study in a tertiary care center.A total of 51 patients with an adrenal lesion underwent [(123)I]IMTO imaging after injection of 185 MBq of [(123)I]IMTO. Sequential planar whole-body scans until 24 hours postinjection and single photon emission computed tomography (SPECT)/computed tomography imaging 4 to 6 hours postinjection were performed.Sensitivity and specificity of [(123)I]IMTO imaging for the noninvasive characterization of adrenal lesions were measured.Adrenocortical tissue showed high and specific tracer uptake with a short investigation time and low radiation exposure. Qualitative analysis of SPECT/computed tomography data resulted in a sensitivity of 89% and a specificity of 85% for differentiating adrenocortical tumors from lesions of nonadrenocortical origin. Receiver-operating characteristic analysis of semiquantitative data revealed a sensitivity of 83% and a specificity of 86% for identification of adrenocortical lesions at a cutoff value of tumor to liver ratio of 1.3.[(123)I]IMTO is a highly specific radiotracer for imaging of adrenocortical tissue with a short investigation time and low radiation exposure. Because of the general availability of SPECT technology, [(123)I]IMTO scintigraphy has the potential to become a widely used tool to noninvasively characterize the biology of adrenal lesions.

Hyperinsulinemia, a condition with excessively high insulin blood levels, is related to an increased cancer incidence. Diabetes mellitus is the most common of several diseases accompanied by hyperinsulinemia. Because an elevated kidney cancer risk was reported for diabetic patients, we investigated the induction of genomic damage by insulin in LLC-PK1 pig kidney cells, rat primary kidney cells, and ZDF rat kidneys. Insulin at a concentration of 5nM caused a significant increase in DNA damage in vitro. This was associated with the formation of reactive oxygen species (ROS). In the presence of antioxidants, blockers of the insulin, and IGF-I receptors, and a phosphatidylinositol 3-kinase inhibitor, the insulin-mediated DNA damage was reduced. Phosphorylation of protein kinase B (PKB or AKT) was increased and p53 accumulated. Inhibition of the mitochondrial and nicotinamide adenine dinucleotide phosphatase oxidase-related ROS production reduced the insulin-mediated damage. In primary rat cells, insulin also induced genomic damage. In kidneys from healthy, lean ZDF rats, which were infused with insulin to yield normal or high blood insulin levels, while keeping blood glucose levels constant, the amounts of ROS and the tumor protein (p53) were elevated in the high-insulin group compared with the control level group. ROS and p53 were also elevated in diabetic obese ZDF rats. Overall, insulin-induced oxidative stress resulted in genomic damage. If the same mechanisms are active in patients, hyperinsulinemia might cause genomic damage through the induction of ROS contributing to the increased cancer risk, against which the use of antioxidants and/or ROS production inhibitors might exert protective effects.

Das medullare Schilddrusenkarzinom ist eine sehr seltene Erkrankung (jahrliche Inzidenz 2–5/Mio. Einwohner) mit variablem, aber haufig eher indolentem klinischem Verlauf. Die Datenlage zur systemischen Therapie hat sich in den letzten Jahren deutlich verbessert. Ziel der vorliegenden Arbeit ist es, die aktuellen Therapieoptionen beim fortgeschrittenen medullaren Schilddrusenkarzinom darzustellen. Selektive Literaturrecherche; Auswertung klinischer Studien. Aufgrund des meist relativ langsamen Tumorwachstums empfiehlt sich selbst bei metastasierter Erkrankung haufig vorerst eine abwartende Strategie bzw. die Evaluation von operativen oder lokal-ablativen Verfahren. Sollte es hierunter zu einem signifikanten Progress kommen, sind mit dem Patienten die systemischen Therapieoptionen zu diskutieren. Basierend auf der Beobachtung, dass bei vielen dieser Tumoren RET-Mutationen bzw. eine gesteigerte Neoangiogenese vorliegen, wurden inzwischen zahlreiche Tyrosinkinaseinhibitoren mit vielversprechenden Ergebnissen untersucht. Seit 2012 ist mit Vandetanib erstmals ein Medikament zur Behandlung des aggressiven und symptomatischen medullaren Schilddrusenkarzinoms zugelassen. Die Datenlage zur klassischen Chemotherapie ist deutlich begrenzter, sodass diese nur im Rahmen individueller Therapiekonzepte eingesetzt wird. Um die Therapie weiter zu verbessern, sollten alle Patienten moglichst innerhalb von klinischen Studien behandelt werden.

Das Nebennierenkarzinom ist eine seltene endokrine Tumorerkrankung, deren Pathogenese noch nicht vollstandig verstanden ist. Ziel des Beitrags ist eine kompakte Darstellung der aktuellen Diagnostik und Therapie des Nebennierenkarzinoms. Selektive Literaturrecherche. Leitsymptome resultieren aus Steroidhormonexzess und der lokalen Raumforderung. Zunehmend erfolgt die Diagnosestellung zufallig im Rahmen einer aus anderen Grunden durchgefuhrten Bildgebung des Abdomens. Fortschritte in Diagnostik und Therapie konnten innerhalb weniger Jahre durch internationale Zusammenarbeit erzielt werden. Die Herangehensweise bei Verdacht auf ein Nebennierenkarzinom ist grundsatzlich interdisziplinar. Der klinische Verdacht wird durch eine umfassende Hormonanalytik und eine standardisierte Schnittbildgebung erhartet. Eine chirurgische R0-Resektion ist das primare Therapieziel. Die meisten Patienten profitieren von einer adjuvanten Therapie mit Mitotan. Bei metastasierter Erkrankung ist die Therapie der ersten Wahl Mitotan alleine oder in Kombination mit Etoposid, Doxorubicin und Cisplatin. Aufgrund der Seltenheit der Erkrankung ist bei Verdacht auf ein Nebennierenkarzinom eine Kontaktaufnahme mit einer spezialisierten Einrichtung ratsam.

OBJECTIVES: Effective management of adverse events (AEs) following vandetanib treatment is important to maximize clinical benefits. We examined whether more frequent contact with vandetanib-treated patients reduced AEs of CTCAE grade 2 or higher.STUDY DESIGN: In this open-label, multicentre, phase III study, patients with locally advanced or metastatic medullary thyroid cancer were randomized to a patient outreach programme (outreach) or a standard AE monitoring schedule (vandetanib control) for 52 weeks. In addition to standard AE monitoring, patients in the outreach arm were contacted every 2 weeks by telephone/during their clinic visit for specific AE questioning related to diarrhoea, nausea, vomiting, fatigue, headache and rash. Patients received vandetanib at 200 or 300 mg/day, depending on the creatinine levels at screening.RESULTS: Altogether, 205 patients were randomized (outreach, n = 103; vandetanib control, n = 102). This study did not meet its primary objective; the mean percentage of time patients experienced at least one AE of grade 2 or higher was higher for the outreach group (51.65%) than for the vandetanib control group (45.19%); the difference was not statistically significant (t statistic: 1.29; 95% CI -3.44 to 16.37%; p = 0.199). The most frequently reported AEs were diarrhoea (56.9% for the outreach group vs. 46.6% for the vandetanib controls), hypertension (36.3 vs. 31.1%), rash (25.5 vs. 24.3%) and nausea (25.5% vs. 18.4%), and the most frequently reported AEs of grade 2 or higher were hypertension (33.3 vs. 23.3%), diarrhoea (26.5 vs. 24.3%) and dermatitis acneiform (11.8 vs. 9.7%).CONCLUSIONS: Additional outreach to patients treated with vandetanib had no impact on the rate or severity of AEs compared to the standard AE monitoring schedule. AEs were consistent with the known safety profile of vandetanib.

Approximately 3-20% of all reticulocytes in blood of healthy persons are immature and transferrin receptor positive (Tf-Ret). Tf-Ret were measured by flow cytometry in 27 patients treated with three different radiopharmaceuticals labeled with (131)I and in 25 healthy controls. Patients were chronically exposed within 6 days to blood doses from 0.18-1.89 Gy (D6). Typically, two-thirds of D6 was administered within the first day (D1). The study had to be confined to intra-subject investigations due to high biological variability of Tf-Ret counts. A significant radiation-induced decline was found in patients D1 doses that were ≥0.5 Gy. Tf-Ret frequency declined during the first 4 to 5 days of nuclear therapy to about 30-60% of its initial value, and increased in the following 3 days without reaching the initial value. At the time of nadir, the relative frequency of Tf-Ret was more depressed than that of reticulocytes and lymphocytes. The relative Tf-Ret frequency at nadir could be fitted to the equation: %-Tf-Ret=exp-(D1/D(o)). D(o) was found to be 1.0 ± 0.4 Gy (Mean ± SEM). The study shows that Tf-Ret frequency in blood might be a good parameter for estimation of the radiation dose to red marrow.