Standard operating procedure (SOP) for cervical ultrasound cine loop video sequences in the follow-up of differentiated thyroid carcinoma (DTC).

RATIONALE AND OBJECTIVES: Cervical ultrasound (US) is crucial in the follow-up of differentiated thyroid cancer (DTC). However, there are no guidelines for its acquisition and documentation, particularly concerning the role of additional video sequences, known as US cine loops (UCL). The aim of this study is to examine the clinical relevance (CR) of a new Standard Operating Procedure (SOP) for cervical UCL in DTC follow-up. MATERIALS AND METHODS: A retrospective analysis was conducted on all UCL examinations of DTC follow-up patients at a tertiary care center between January 2010 and February 2018 to determine their clinical significance. The patients were divided into two groups: those with no documented CR (UCL-nCR) and those with documented CR (UCL-CR). The study reviewed the respective written medical US reports that were validated by experienced residents. The UCL-CR were categorized in: confirmation of a suspicious finding that was identified during conventional live US (UCL-CRcon), identification of a suspicious finding that was not identified during conventional live US (UCL-CRide), and invalidation of a suspicious finding that was identified during conventional live US (UCL-CRinv). RESULTS: A total of 5512 UCLs in 652 DTC patients were analyzed, with 71.5% women and a mean age of 50 years. More than 90% of the tumors were low-risk at initial staging. The mean number of UCLs per patient was 8.5 ± 4.6. Overall, 95 cases of UCL-CR were identified in 82 patients (12.6%), with a patient-based number needed to scan of 8. UCL-CRinv was the most common type of UCL-CR, accounting for 77 (81.1%) of cases. The occurrences of 12 UCL-CRcon (12.6%) and 6 UCL-CRide (6.3%) were correspondingly less frequent. The diagnosis of UCL-CR was confirmed in 91.6% of cases during the clinical course. CONCLUSIONS: In 12.6% of the patients, the additional acquisition and archiving of cervical UCL revealed clinical relevance in the course of DTC disease. The invalidation of suspicious findings through the retrospective analysis of former UCL occurred as the most significant benefit of this method. The UCL SOP can be easily and quickly integrated into the US workflow.

Angiographic Aspects of Transarterial Radioembolization: A Comparison of Technical Options to Avoid Extrahepatic Microsphere Depositions.

The influence of the interventional treatment approach for transarterial radioembolization (TARE) on the incidence of extrahepatic microsphere depositions and to angiographic complications was evaluated. In total, 398 TARE cycles were analyzed. Interventional treatment approaches were classified as single treatment position (TP) with interventional occlusion (IO), multiple TPs without IO, and multiple TPs with IO. Correlations with extrahepatic microsphere depositions, angiographic complications, and periprocedural clinical events were performed. Alternative treatment strategies were evaluated. Applications from multiple TPs could have ensured the safe application of microspheres in 48.2% of cases that were originally performed from a single TP after IO. Extrahepatic microsphere accumulations were detected after 5.2%, 5.3%, and 1.5% of TARE procedures from a single TP without IO, a single TP with IO, and multiple TPs without IO, respectively. Applications from multiple TPs did not increase angiographic complications. During the 30-day follow-up, nausea/vomiting and upper abdominal discomfort were observed more frequently in the group with IO than in the group without IO (7.9%/4.6% and 9.2%/5.9%, respectively). In many TARE procedures, the same target liver can be treated from multiple TPs instead of a single TP, reducing the need for the interventional occlusion of aberrant arteries and potential extrahepatic microsphere depositions.

The synthesis of N,1,4-tri(alkoxy-hydroxybenzyl)-1,4-diazepane-amines: investigations on reaction characteristics and mechanism.

1,4-Diazepane-6-amine (DAZA) can be alkylated with three 2-hydroxybenzyl pendant arms, resulting in hexadentate chelators suitable for coordination of radiometals like 68Ga. These chelators, N,1,4-tri(alkoxy-2-hydroxybenzyl)-DAZA, can be produced via a one-pot synthesis, with the first step being a carbonyl amine condensation of DAZA with two respective 4-alkoxy-2-hydroxybenzaldehydes, followed by reductive amination with sodium borohydride. While the first step of this reaction is predictable, the subsequent reductive amination can result in either mono-, di- or tri(alkoxy-hydroxybenzyl)-DAZA compounds. Seeking to identify dependencies that might allow a specific reaction control towards the formation of either of the three possible products, and particularly towards the favoured trialkylated DAZA compounds, a variety of synthesis trials were performed. Additionally, computational methods were employed to evaluate the underlying reaction mechanism. Synthesis trials verified that the trialkylated DAZA compounds are formed via direct reductive amination of the dialkylated DAZA compounds. Subsequently, a synthetic method was established, leading to an increase in the percentage of the trialkylated DAZA compounds, which allowed the successful isolation of those hexadentate chelators. Additionally, an alternative pathway proceeding via aminal C-N bond insertion of an attacking third carbonyl moiety was evaluated by means of quantum chemical calculations but so far remains entirely hypothetical.

Clinical Results of Holmium-166 Radioembolization with Personalized Dosimetry for the Treatment of Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) with 166Ho-loaded microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), introduced in 2010. This study evaluates the clinical outcome of patients with HCC who underwent 166Ho-TARE with personalized dosimetry. Twenty-seven patients with 36 TARE procedures were analyzed. Treatment planning, execution, and evaluation was possible without complications in all cases. At the 3-month follow-up, disease control in the treated liver was achieved in 81.8% of patients (complete remission, partial remission, and stable disease in 36.4%, 31.8%, and 13.6%, respectively). The median overall survival (OS) was 17.2 months, and progression-free survival (PFS) in the treated liver was 11 months. Statistically significant positive correlations were observed between the achieved radiation dose for the tumor and both PFS (r = 0.62, p < 0.05) and OS (r = 0.48, p < 0.05), suggesting a direct dose-response relationship. The calculated achieved dose was 8.25 Gy lower than the planned dose, with relevant variance between planned and achieved doses in individual cases. These results confirm the efficacy of the 166Ho-TARE holmium platform and underscore the potential of voxel-based, personalized dosimetry to improve clinical outcomes.

Dependence of Renal Uptake on Kidney Function in [68Ga]Ga-PSMA-11 PET/CT Imaging.

(1) Background: PSMA ligand PET/CT is increasingly important for diagnostics of prostate cancer and other tumor diseases. In particular, the radiopharmaceutical [68Ga]Ga-PSMA-11 is widely used. Besides its tumor-specific binding, the uptake within the kidneys is dominant and seems to visualize the renal cortex specifically. Kidney diseases may alter the uptake of radiopharmaceuticals. Therefore, the correlation between renal uptake in PET/CT imaging and renal function should be investigated. (2) Methods: A group of 103 male patients were retrospectively evaluated for eGFR according to the CKD-EPI equation, tracer uptake intensity (SUVmax, SUVpeak, SUVmean), the molecular volume of the renal cortex, morphological kidney size, and total renal uptake. Manual and three different computer-assisted contouring methods (thresholds at 50% of SUVmax, 30% of SUVmax, and absolute SUV of 20) were used for measurements. Correlations between parameters were calculated using linear regression models. (3) Results: Renal SUVmax, SUVpeak, and SUVmean do not correlate with eGFR for manual or computer-assisted measurements. In contrast, molecular cortex volume shows a moderate correlation with eGFR (R2 = 0.231, p < 0.001), superior to morphological kidney size. A contouring threshold of 30% of SUVmax outperformed the other settings for renal cortex volume and total renal uptake. (4) Conclusions: Renal uptake of [68Ga]Ga-PSMA-11 cannot predict eGFR, but the functional renal cortex can be quantified by PET/CT imaging.

Transarterial Radioembolization (TARE) in Patients with Hepatocellular Carcinoma: A Comparison of Palliative with Bridging-to-Transplant Concepts.

We investigated transarterial radioembolization (TARE) as a palliative measure and bridging-to-transplant therapy in hepatocellular carcinoma (HCC) patients. A total of 167 patients (50 bridging, 117 palliative) with 245 TARE procedures were assessed. Fourteen patients underwent subsequent liver transplantation (LT). Patients undergoing LT exhibited significantly prolonged progression-free survival (PFS) compared to those with bridging-without-transplant (p = 0.033). No significant differences were observed between patients with bridging-without-transplant and palliative cases (p = 0.116). Median overall survival (OS) post-TARE was 16.6 months, with estimated OS rates at 6/12 months of 82.0%/60.5%, respectively. Patients who underwent LT demonstrated statistically significantly longer OS compared to those with bridging-without-transplant (p = 0.001). No marked outcome distinctions were found between bridging-without-transplant and palliative groups. The findings underscored the superiority of LT over alternative treatments. TARE served as an important component in non-LT scenarios, allowing for subsequent therapeutic options. The study reflected the highly variable and complex situations of patients with HCC, emphasizing the need for further investigations to define an optimal multimodal approach.

[Normal values for adult thyroid volume on ultrasound - where do they come from and how should they be evaluated?] / Sonographische Normwerte für das Schilddrüsenvolumen Erwachsener ­ woher kommen sie und wie sind sie zu bewerten?

The upper limit for the thyroid volume is 18 ml for women and 25 ml for men. These reference values are used and taught in many clinics and practices across several disciplines. The thyroid volume is a relevant factor for the treatment course. But where do the standard values for thyroid volumes come from, what kind of studies have been carried out to establish them? Should these upper limits be used as an universal standard in clinical routine, and which factors can influence the physiological organ size? The following article is dedicated to a critical review of the commonly used reference values for the thyroid volume of adults.

[Technical innovations to optimize ultrasound imaging]. / Technische Innovationen zur Optimierung der Ultraschallbildgebung.

Due to the high incidence of thyroid disease, ultrasound examination of the neck has high priority in many nuclear medicine departments. A precise sonogram with high spatial resolution and image sharpness over the entire imaging area, combined with minimal artifacts, is the prerequisite for meeting the demand for high diagnostic accuracy in modern medicine. In the last 20-30 years, a number of significant technical innovations have been implemented, such as the development of the matrix array, electronic image focusing, realtime compound imaging, artifact limitation by speckle reduction and harmonic imaging, as well as the possibility to extend the field of view.

[Standardized acquisition and documentation of cine loops on conventional thyroid ultrasound]. / Standardisierte Akquisition und Dokumentation von Videosequenzen bei der konventionellen Schilddrüsensonografie.

Ultrasound is the basic imaging method for the assessment of the thyroid gland. Due to the high prevalence of structural disease, the examination procedure is used very frequently in Germany, in many cases in the context of follow-up. The assessment of thyroid pathologies and their dynamics is subjected to relevant inter- and intraobserver variability. Findings that were not identified during live ultrasound cannot be assessed retrospectively. Applying an SOP for the acquisition and documentation of standardized video sequences of ultrasound images (so-called cine loops), allows for a secondary retrospective evaluation of the thyroid gland, taking into account previously acquired images analogous to other cross-sectional imaging methods such as CT or MRI. The cine loops can be acquired by non-physician personnel, stored to the local PACS and used for educational and research purposes.

68 Ga-Oxine-Labeled Erythrocytes as a New PET Tracer for the Localization of Gastrointestinal Bleeding.

ABSTRACT: A 69-year-old man presented with recurring drops in hemoglobin levels and suspected gastrointestinal bleeding. Endoscopy did not show a site of bleeding so further examinations became necessary. Scintigraphy and SPECT/CT with 99m TcO 4- -labeled red blood cells were performed without evidence of a hemorrhage. Based on an established protocol for splenic PET/CT, autologous erythrocytes can be labeled with 68 Ga-oxine and used as a tracer for the localization of active bleeding sites. In the patient, PET/CT with 68 Ga-oxine-labeled undamaged erythrocytes was performed successfully and revealed a hemorrhage of the gastric corpus that was confirmed and treated by endoscopy.

Image-Guided Fine-Needle Aspiration Cytology for BRCA Mutation Assessment of PSMA-Positive Lymph Node Metastases in a Patient With Metastatic Castration-Resistant Prostate Cancer.

ABSTRACT: A 64-year-old man with metastatic castration-resistant prostate cancer presented for prostate-specific membrane antigen (PSMA) PET/CT in preparation for 177 Lu-PSMA radioligand therapy. For precedent BRCA mutation assessment, fine-needle aspiration cytology of 2 PSMA-positive lymph node metastases was conducted. The acquired material was suitable for next-generation sequencing-based gene panel diagnostics and did not show a BRCA1 / 2 mutation, thus PSMA radioligand therapy was initiated. Fine-needle aspiration cytology of lymph node metastases may be a viable option in evaluating further therapeutic alternatives.

[Necrosis of the tongue as a clinical manifestation of giant cell arteritis]. / Zungennekrose als klinische Manifestation einer Riesenzellarteriitis.

An 83-year-old male patient presented due to a 3-week history of swelling of the tongue with tongue pain on eating, yellowish plaques, and a gray-brown lesion in the anterior portion of the tongue. Sudden loss of vision in the left eye and temporal headache occurred 3 days before presentation. Due to elevated C­reactive protein, sonography of the supraaortic arteries as well as positron emission tomography/computed tomography was performed. Imaging revealed inflammation of the great arteries as well as a halo sign on ultrasound of the temporal artery. Thus, a diagnosis of giant cell arteritis with necrosis of the tongue was made. Immunosuppressive therapy with glucocorticoids was initiated. Necrosis of the tongue is a rare manifestation of giant cell arteritis that requires immediate immunosuppressive therapy to prevent further complications to the tongue (e.g., complete necrosis of the tongue, superinfection, tongue amputation).

Noninvasive Verification of a Very Small Intraocular Prostate Carcinoma Metastasis by 68Ga-PSMA-11 PET/CT.

ABSTRACT: A male patient underwent 68Ga-PSMA-11 PET/CT for the evaluation of a suspected intraocular metastasis in the right eye. Although the choroidal thickening was very small (4 × 2 mm), and ophthalmoscopy as well as MRI were inconclusive, PET/CT imaging showed distinct PSMA expression in the suspected lesion, confirming prostate cancer metastasis. The ability of dedicated PSMA ligand PET/CT imaging to detect small metastases, even with 68Ga-labeled ligands, has been demonstrated. Therefore, the use of further invasive diagnostic procedures could be avoided. Thus, the possibility of detecting intraocular metastases of prostate cancer should be considered in routine PET/CT imaging.

Radionuclide Cisternography with [64Cu]Cu-DOTA.

Radionuclide cisternography (RNC) is a method for conducting imaging of the cerebrospinal system and can be used to identify cerebrospinal fluid leaks. So far, RNC has commonly employed radiopharmaceutical agents suitable only for single-photon emission tomography techniques, which are thus lacking in terms of image resolution and can potentially lead to false-negative results. Therefore, [64Cu]Cu-DOTA was investigated as an alternative radiopharmaceutical for RNC, employing positron emission tomography (PET) instead of single-photon emission tomography. A formulation of [64Cu]Cu-DOTA was produced according to the guidelines for good manufacturing practice. The product met the requirements of agents suitable for intrathecal application. [64Cu]Cu-DOTA was administered to a patient and compared to the approved scintigraphic RNC agent, [111In]In-DTPA. While no cerebrospinal fluid leak was detected with [111In]In-DTPA, [64Cu]Cu-DOTA RNC exhibited a posterolateral leak between the vertebral bodies C1 and C2. Thus, in this patient, PET RNC with [64Cu]Cu-DOTA was superior to RNC with [111In]In-DTPA. Since radiopharmaceuticals have a very good safety profile regarding the occurrence of adverse events, PET RNC with [64Cu]Cu-DOTA may become an attractive alternative to scintigraphic methods, and also to computed tomography or magnetic resonance imaging, which often require contrast agents, causing adverse events to occur much more frequently.

Clinical Results of Transarterial Radioembolization (TARE) with Holmium-166 Microspheres in the Multidisciplinary Oncologic Treatment of Patients with Primary and Secondary Liver Cancer.

Holmium-166 microspheres are used for the transarterial radioembolization (TARE) treatment of primary and secondary liver cancers. In this study, its efficacy regarding local tumor control and integration into the oncological treatment sequence of the first 20 patients treated in our institution were examined. A total of twenty-nine 166Ho-TARE procedures were performed to treat hepatocellular carcinoma (HCC, fourteen patients), metastatic colorectal cancer (mCRC, four patients), intrahepatic cholangiocarcinoma (ICC, one patient), and hemangioendothelioma of the liver (HE, one patient). In eight patients, 166Ho-TARE was the initial oncologic treatment. In patients with HCC, the median treated-liver progression-free survival (PFS), overall PFS, and overall survival after 166Ho-TARE were 10.3, 7.3, and 22.1 months; in patients with mCRC, these were 2.6, 2.9, and 20.6 months, respectively. Survival after 166Ho-TARE in the patients with ICC and HE were 5.2 and 0.8 months, respectively. Two patients with HCC were bridged to liver transplantation, and one patient with mCRC was downstaged to curative surgery. In patients with HCC, a median treatment-free interval of 7.3 months was achieved. In line with previous publications, 166Ho-TARE was a feasible treatment option in patients with liver tumors, with favorable clinical outcomes in the majority of cases. It was able to achieve treatment-free intervals, served as bridging-to-transplant, and did not prevent subsequent therapies.

The effect of butylscopolamine on [18F]FDG uptake in the gastrointestinal tract is negligible and regionally variable.

BACKGROUND: Butylscopolamine (or hyoscine butylbromide, trade name Buscopan®) is occasionally administered as a premedication to reduce non-specific FDG uptake in the gastrointestinal tract based on its antiperistaltic effect. To date, there are no consistent recommendations for its use. The aim of this study was to quantify the reduction in intestinal and non-intestinal uptake by butylscopolamine administration and to derive relevance for clinical evaluation. RESULTS: 458 patients (PET/CT for lung cancer) were retrospectively reviewed. 218 patients with butylscopolamine and 240 patients without butylscopolamine had comparable characteristics. While the SUVmean in the gullet/stomach and small intestine was significantly reduced with butylscopolamine, the colon and rectum/anus showed no difference. The liver and salivary glands showed a reduced SUVmean, while skeletal muscle and blood pool were unaffected. An effect of butylscopolamine was particularly evident in men and patients under 65 years of age. There was no difference in the perceived confidence in the assessment of intestinal findings in the subjective evaluation, although in the butylscopolamine group further diagnostics appeared advisable more frequently. CONCLUSIONS: Butylscopolamine reduces gastrointestinal FDG accumulation only in selected segments and, despite a significant effect, only to a small extent. A general recommendation for the use of butylscopolamine cannot be derived from these results, its use for specific issues could be considered individually.

A Novel Breast Cancer Xenograft Model Using the Ostrich Chorioallantoic Membrane-A Proof of Concept.

The avian chorioallantoic membrane (CAM) assay has attracted scientific attention in cancer research as an alternative or complementary method for in vivo animal models. Here, we present a xenograft model based on the ostrich (struthio camelus) CAM assay for the first time. The engraftment of 2 × 106 breast cancer carcinoma MDA-MB-231 cells successfully lead to tumor formation. Tumor growth monitoring was evaluated in eight fertilized eggs after xenotransplantation. Cancer cells were injected directly onto the CAM surface, close to a well-vascularized area. Histological analysis confirmed the epithelial origin of tumors. The CAM of ostrich embryos provides a large experimental surface for the xenograft, while the comparably long developmental period allows for a long experimental window for tumor growth and treatment. These advantages could make the ostrich CAM assay an attractive alternative to the well-established chick embryo model. Additionally, the large size of ostrich embryos compared to mice and rats could help overcome the limitations of small animal models. The suggested ostrich model is promising for future applications, for example, in radiopharmaceutical research, the size of the embryonal organs may compensate for the loss in image resolution caused by physical limitations in small animal positron emission tomography (PET) imaging.