Additional Value of Pertechnetate Scintigraphy to American College of Radiology Thyroid Imaging Reporting and Data Systems and European Thyroid Imaging Reporting and Data Systems for Thyroid Nodule Classification in Euthyroid Patients.

Thyroid nodules are common yet remain a diagnostic challenge. While ultrasound and Thyroid Imaging Reporting and Data Systems (TIRADS) are accepted as standard, the use of thyroid scintigraphy in euthyroid patients is debated. The European Association of Nuclear Medicine advocates it, whereas the American Thyroid Association and European Thyroid Association do not.

Diagnostic Performance of [F]TFB PET/CT Compared with Therapeutic Activity [I]Iodine SPECT/CT and [F]FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma.

[F]tetrafluoroborate ([F]TFB) is an emerging PET tracer with excellent properties for human sodium iodide symporter (NIS)-based imaging in patients with differentiated thyroid cancer (DTC). The aim of this study was to compare [F]TFB PET with high-activity posttherapeutic [I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [F]FDG PET/CT in suspected dedifferentiation. Twenty-six patients treated with high-activity radioactive [I]iodine therapy (range, 5.

Postoperative thyroglobulin as a yard-stick for radioiodine therapy: decision tree analysis in a European multicenter series of 1317 patients with differentiated thyroid cancer.

Purpose: An accurate postoperative assessment is pivotal to inform postoperative I treatment in patients with differentiated thyroid cancer (DTC). We developed a predictive model for post-treatment whole-body scintigraphy (PT-WBS) results (as a proxy for persistent disease) by adopting a decision tree model.

Methods: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, TSH, and Tg were identified as potential predictors and were put into regression algorithm (conditional inference tree, ctree) to develop a risk stratification model for predicting the presence of metastases in PT-WBS.

Predictors of Anxiety and Depression in Differentiated Thyroid Cancer Survivors: Results of a Cross-Sectional Study.

Despite an excellent survival rate, impairments are recognized in the quality of life and emotional well-being of differentiated thyroid cancer (DTC) survivors. Predictors for anxiety and depression in DTC patients are not well characterized. To identify predictors for anxiety and depression in DTC survivors.

Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options.

In rare diseases such as adrenocortical carcinoma (ACC), in silico analysis can help select promising therapy options. We screened all drugs approved by the FDA and those in current clinical studies to identify drugs that target genomic alterations, also known to be present in patients with ACC. We identified FDA-approved drugs in the My Cancer Genome and National Cancer Institute databases and identified genetic alterations that could predict drug response.

Enhancing Radioiodine Incorporation into Radioiodine-Refractory Thyroid Cancer with MAPK Inhibition (ERRITI): A Single-Center Prospective Two-Arm Study.

Purpose: Restoration of iodine incorporation (redifferentiation) by MAPK inhibition was achieved in previously radioiodine-refractory, unresectable thyroid carcinoma (RR-TC). However, results were unsatisfactory in BRAFV600E-mutant (BRAF-MUT) RR-TC. Here we assess safety and efficacy of redifferentiation therapy through genotype-guided MAPK-modulation in patients with BRAF-MUT or wildtype (BRAF-WT) RR-TC.

Anaplastic thyroid cancer: genome-based search for new targeted therapy options.

Objective: Anaplastic thyroid cancer (ATC) is one of the most lethal human cancers with meager treatment options. We aimed to identify the targeted drugs already approved by the Food and Drug Administration (FDA) for solid cancer in general, which could be effective in ATC.

Design: Database mining.

Targeted Therapy of Papillary Thyroid Cancer: A Comprehensive Genomic Analysis.

Background: A limited number of targeted therapy options exist for papillary thyroid cancer (PTC) to date. Based on genetic alterations reported by the "The Cancer Genome Atlas (TCGA)", we explored whether PTC shows alterations that may be targetable by drugs approved by the FDA for other solid cancers.

Methods: Databases of the National Cancer Institute and MyCancerGenome were screened to identify FDA-approved drugs for targeted therapy.

Minimal extrathyroid extension in papillary micro carcinoma of the thyroid is an independent risk factor for relapse through lymph node and distant metastases.

Minimal extrathyroid extension (mETE) is no longer considered in the new 8th edition of the AJCC/UICC staging system. Therefore, papillary thyroid microcarcinoma with mETE previously staged as pT3 will now be staged as pT1a and most likely not receive adjuvant radioiodine therapy. However, it remains unclear if mETE is associated with higher aggressiveness in papillary thyroid microcarcinoma.

Clinical Presentation, Treatment, and Outcome of Parathyroid Carcinoma: Results of the NEKAR Retrospective International Multicenter Study.

Objective: In this retrospective cohort study, we describe the clinical presentation and workup of parathyroid carcinoma (PC) and determine its clinical prognostic parameters. Primary outcome was recurrence free survival.

Summary Background Data: PC is an orphan malignancy for which diagnostic workup and treatment is not established.

Impact of FDG-PET on therapy management and outcome of differentiated thyroid carcinoma patients with elevated thyroglobulin despite negative iodine scintigraphy.

Aim:  The objective of this study was to assess the impact of implementing FDG-PET imaging in treatment algorithms for differentiated thyroid cancer with suspected recurrence. Primary end points were overall, event-free and disease-specific survival. Secondary end points were therapies, disease control and the sensitivity and specificity of PET imaging.

The Role of Radiotherapy for Patients With Thyroid Cancer in the Modern Era.

Background/aim: Thyroid cancer (TC) is a relatively rare malignancy. The mainstay treatment is surgery followed by radioactive iodine (RAI) and medical systemic treatments. The role of external beam radiotherapy (EBRT) in TC is controversial regarding the survival benefits.

Incremental diagnostic value of [F]tetrafluoroborate PET-CT compared to [I]iodine scintigraphy in recurrent differentiated thyroid cancer.

Introduction: Efficient therapy of recurrent differentiated thyroid cancer (DTC) is dependent on precise molecular imaging techniques targeting the human sodium iodide symporter (hNIS), which is a marker both of thyroid and DTC cells. Various iodine isotopes have been utilized for detecting DTC; however, these come with unfavorable radiation exposure and image quality ([I]iodine) or limited availability ([I]iodine). In contrast, [F]tetrafluoroborate (TFB) is a novel radiolabeled PET substrate of hNIS, results in PET images with high-quality and low radiation doses, and should therefore be suited for imaging of DTC.

Optimizing the Biodistribution of Radiofluorinated Barbiturate Tracers for Matrix Metalloproteinase Imaging by Introduction of Fluorescent Dyes as Pharmacokinetic Modulators.

Dysregulated expression or activation of matrix metalloproteinases (MMPs) is observed in many kinds of life-threatening diseases. Therefore, MMP imaging-for example, with radiolabeled MMP inhibitors (MMPIs)-potentially represents a valuable tool for clinical diagnostics using noninvasive single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. Despite numerous preclinical imaging approaches, translation to a clinical setting has not yet been successful.

Prevalence of hyperfunctioning thyroid nodules among those in need of fine needle aspiration cytology according to ATA 2015, EU-TIRADS, and ACR-TIRADS.

Purpose: Given the large number of patients with thyroid nodules, improvement of the specificity of current ultrasound-based thyroid nodule classification systems (ATA, EU-TIRADS, and ACR-TIRADS) is warranted to reduce the number of diagnostic thyroidectomies. Thyroid scintigraphy has been shown to demonstrate hyperfunctional nodules, associated with a low malignancy risk, in euthyroid patients. However, it is not known if thyroid scintigraphy could improve specificity of current classification systems.

[Outpatient quality of care for permanent postoperative hypoparathyroidism].

Background: Postoperative hypoparathyreoidism can cause severe symptoms, relevant sequelae and far reaching impairments of quality of life. Socio-economic effects are considerable. Individual follow-up of patients at risk could improve quality of care.

Proline-based hydroxamates targeting the zinc-dependent deacetylase LpxC: Synthesis, antibacterial properties, and docking studies.

The Zn-dependent deacetylase LpxC is an essential enzyme in Gram-negative bacteria, which has been validated as antibacterial drug target. Herein we report the chiral-pool synthesis of novel d- and l-proline-derived 3,4-dihydroxypyrrolidine hydroxamates and compare their antibacterial and LpxC inhibitory activities with the ones of 4-monosubstituted and 3,4-unsubstituted proline derivatives. With potent antibacterial activities against several Gram-negative pathogens, the l-proline-based tertiary amine 41g ((S)-N-hydroxy-1-(4-{[4-(morpholinomethyl)phenyl]ethynyl}benzyl)pyrrolidine-2-carboxamide) was found to be the most active antibacterial compound within the investigated series, also showing some selectivity toward EcLpxC (K = 1.

[Risk Factors for Permanent Postoperative Hypoparathyreoidism].

Background: Permanent postoperative hypoparathyreoidism remains the most frequent complication after total thyreoidectomy with severe long-term morbidity, impairment of quality of life and economic implications.

Objective: Identification of risk factors for permanent postoperative hypoparathyreoidism.

Material And Methods: 420 patients received total thyreoidectomy in our endocrine centre between 08/2012 und 08/2014, of whom 382 were included in the study.

177Lu-DOTATATE Therapy in Radioiodine-refractory Differentiated Thyroid Cancer: A Single Center Experience.

Introduction: Patients with radioiodine-refractory differentiated thyroid cancer (RrDTC) have a rather poor prognosis and are in need of novel treatments. As RrDTCs can in some cases express somatostatin receptors (SSRT), targeting of these receptors by Ga/Lu-DOTATATE could evolve as a novel theranostic option.

Methods: Five RrDTC patients with limited further therapeutic options and documented expression of SSRT using Ga-DOTATATE-PET/CT received 2 to 4 cycles of PRRT with Lu-DOTATATE.

Design, (Radio)Synthesis, and in Vitro and in Vivo Evaluation of Highly Selective and Potent Matrix Metalloproteinase 12 (MMP-12) Inhibitors as Radiotracers for Positron Emission Tomography.

Dysregulated levels of activated matrix metalloproteinases (MMPs) are linked to different pathologies, such as cancer, atherosclerosis, neuroinflammation, and arthritis. Therefore, imaging of MMPs with positron-emission tomography (PET) represents a powerful tool for the diagnosis of MMP-associated diseases. Moreover, to distinguish between the distinct functions and roles of individual MMPs in particular pathophysiological processes, their specific imaging must be realized with radiolabeled tracers, such as fluorine-18-labeled MMP inhibitors (MMPIs).

Evaluation of I scintigraphy and stimulated thyroglobulin levels in the follow up of patients with DTC: a retrospective analysis of 1420 patients.

Aim: To study the clinical yield of diagnostic whole body I scintigraphy (DxWBS) in the follow-up of differentiated thyroid carcinoma (DTC) patients in relation to stimulated thyroglobulin (sTg) in the initial post-ablation setting, as well as in the setting of repeated monitoring in course of further DTC follow-up.

Methods: Data of 1420 thyroidectomized and radioiodine remnant-ablated DTC patients following a well-defined therapy and standardized follow-up protocol were evaluated. DxWBS and sTg were evaluated separately and in combination for various follow-up time points.

Novel Potent Proline-Based Metalloproteinase Inhibitors: Design, (Radio)Synthesis, and First in Vivo Evaluation as Radiotracers for Positron Emission Tomography.

As dysregulation of matrix metalloproteinase (MMP) activity is associated with a wide range of pathophysiological processes like cancer, atherosclerosis, and arthritis, MMPs represent a valuable target for the development of new therapeutics and diagnostic tools. We herein present the chiral pool syntheses, in vitro evaluation, and SAR studies of a series of d- and l-proline- as well as of (4R)-4-hydroxy-l-proline-derived MMP inhibitors possessing general formula 1. Some of the synthesized hydroxamic acids were found to be potent MMP inhibitors with IC values in the nanomolar range, also demonstrating no off-target effects toward the other tested Zn-dependent metalloproteases (ADAMs and meprins).

[(68)Ga]DOTATATE PET/MRI and [(18)F]FDG PET/CT are complementary and superior to diffusion-weighted MR imaging for radioactive-iodine-refractory differentiated thyroid cancer.

Purpose: The purpose of this study was to determine whether [(68)Ga]DOTATATE PET/MRI with diffusion-weighted imaging (DWI) can replace or complement [(18)F]FDG PET/CT in patients with radioactive-iodine (RAI)-refractory differentiated thyroid cancer (DTC).

Methods: The study population comprised 12 patients with elevated thyroglobulin and a negative RAI scan after thyroidectomy and RAI remnant ablation who underwent both [(18)F]FDG PET/CT and [(68)Ga]DOTATATE PET/MRI within 8 weeks of each other. The presence of recurrent cancer was evaluated on a per-patient, per-organ and per-lesion basis.

Fluorinated matrix metalloproteinases inhibitors--Phosphonate based potential probes for positron emission tomography.

Fluorine-containing inhibitors of matrix metalloproteinases (MMPs) can serve as lead structures for the development of (18)F-labeled radioligands. These compounds might be useful as non-invasive imaging probes to characterize pathologies associated with increased MMP activity. Results with a series of fluorinated analogs of a known biphenyl sulfonamide inhibitor have shown that fluorine can be incorporated into two different positions of the molecular scaffold without significant loss of potency in the nanomolar range.