In-vivo imaging markers of neuronal changes related to Alzheimer’s disease (AD) are ideally suited to be employed as diagnostic markers for early and differential diagnosis of AD as well as for the assessment of neurobiological effects of medical treatments in clinical trials. Novel molecular imaging techniques enable in-vivo detection of cerebral amyloid pathology, whereas magnetic resonance imaging (MRI)-based techniques, such as volumetric MRI and diffusion tensor imaging (DTI), provide structural lesion markers that allow tracking disease progression from preclinical through predementia to clinically manifest stages of AD. However, a widespread clinical use of these imaging biomarkers is hampered by considerable multi-centric variability related to differences in scanner hardware and acquisition protocols, but also by the lack of internationally agreed upon standards for analytic design and employed quantitative metrics. Several strategies for reducing multicenter variability in imaging measures have been proposed, including homogenization of the acquisition settings across scanner platforms, stringent quality assurance procedures, and artifact removal by means of post-acquisition image processing techniques. In addition, selection of appropriate statistical models to account for remaining multicenter variability in the data can further improve the accuracy and reproducibility of study results. The first projects for international standardization of image analysis methods and derived quantitative metrics have emerged recently for volumetric MRI measures. In contrast, the standardization and establishment of DTI-derived measures within a multicenter context are less well developed. Although molecular imaging techniques are already widely used in multicenter settings, sources of variability across sites and appropriate methods to reduce multicenter effects are still not explored in detail. Comparability of neuroimaging measures as AD biomarkers in worldwide clinical settings will finally depend on the establishment of internationally agreed upon standards for image acquisition, quality assurance, and employed quantitative metrics.

Abstract: The utility of amyloid positron emission tomography (PET) for the etiological diagnosis of dementia and its impact on functional status of patients in routine care are currently unclear. Here, we describe the design of ENABLE, a randomized controlled two-armed coverage with evidence development (CED) study in Germany. Approximately 1126 patients with mild to moderate dementia of unclear etiology will be randomly assigned to either an amyloid PET or a no amyloid PET group. Patients will be followed-up for 24 months. The study has been registered at the German Clinical Trials Register (https://drks.de/search/de/trial/DRKS00030839) with the registration code DRKS00030839. The primary endpoint of ENABLE is the ability to perform functional activities of daily living at 18 months. Secondary endpoints include change in diagnosis, diagnostic confidence, and cognitive and clinical outcomes of patients. We expect that the CED study ENABLE will inform about patient relevant effects of amyloid PET in routine care. Furthermore, we anticipate that ENABLE will support physicians' and payers' decisions on provision of health care for patients with dementia. Highlights Study design focuses on the usefulness of amyloid positron emission tomography (PET) in routine care. Study design addresses the patient-relevant effect of amyloid PET. Patient representatives were involved in the creation of the study design. The study will help improve routine care for people with dementia

In dieser Schrift werden 5 retrospektive Studien zur klinischen Implementierung des theranostischen Ansatzes und zur Optimierung von Bildgebungs- und Dosimetrieverfahren bei nuklearmedizinischer Diagnostik und Therapie des metastasierten kastrationsrefraktären Prostatakarzinoms und von Neuroendokrinen Neoplasien zusammengefasst. Die Ergebnisse zeigen, dass die Anwendung des theranostischen Paars Ga-68/Lu-177 eine sichere und klinisch wirksame Methode ist. Die konsequente Verknüpfung von Ga-68-PET/CT und intratherapeutischer Lu-177-SPECT/CT kann einen Beitrag zur weiteren Optimierung leisten.ger