Comparison of the Hematotoxicity of PRRT with Lutathera and Locally Manufactured Lu-HA-DOTATATE in Patients with Neuroendocrine Tumors and the Impact of Different Application Intervals.

Background/objectives: Peptide Receptor Radionuclide Therapy (PRRT) is approved for patients with inoperable, progressive and/or metastatic well-differentiated NETs. Before the approval of Lutathera, locally manufactured Lu-HA-DOTATATE was used on a regular basis in clinical routine. The aim of this study was (1) to compare the hematotoxicity of locally manufactured Lu-HA-DOTATATE with Lutathera in GEP-NET patients and (2) to compare the recommended treatment interval of 8 weeks between each cycle to a prolonged scheme of up to 11 weeks for both Lu-HA-DOTATATE and Lutathera.

Partial volume effect correction impairs the diagnostic utility of [F]-THK-5351 PET in nonfluent-agrammatic variant primary progressive aphasia.

Objectives: Partial volume effects in positron emission tomography occur frequently in neurodegenerative diseases due to increasing cortical atrophy during the disease course, and fronto-temporal dementia is often characterized by severe atrophy. The aim of this study was to challenge partial volume effect correction (PVEC) in patients with nonfluent-agrammatic variant primary progressive aphasia (nfv-PPA) imaged with [F]-THK-5351 PET a marker of reactive neuroinflammatory astrogliosis as well as tau-binding.

Methods: Patients with nfv-PPA (n = 20) were imaged with [F]-THK-5351 PET accompanied by structural magnetic resonance tomography imaging (MRI).

Neuronal and oligodendroglial, but not astroglial, tau translates to in vivo tau PET signals in individuals with primary tauopathies.

Tau PET has attracted increasing interest as an imaging biomarker for 4-repeat (4R)-tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau PET signals is still unclear. Therefore, we performed a translational study using a broad spectrum of advanced methodologies to investigate the sources of [F]PI-2620 tau PET signals in individuals with 4R-tauopathies, including a pilot PET autopsy study in patients.

Regional desynchronization of microglial activity is associated with cognitive decline in Alzheimer's disease.

Background: Microglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative disease. We addressed the existence of a microglia connectome and investigated microglial desynchronization as an AD biomarker.

Towards multicenter β-amyloid PET imaging in mouse models: A triple scanner head-to-head comparison.

Aim: β-amyloid (Aβ) small animal PET facilitates quantification of fibrillar amyloidosis in Alzheimer's disease (AD) mouse models. Thus, the methodology is receiving growing interest as a monitoring tool in preclinical drug trials. In this regard, harmonization of data from different scanners at multiple sites would allow the establishment large collaborative cohorts and may facilitate efficacy comparison of different treatments.

Tau accumulation is associated with dopamine deficiency in vivo in four-repeat tauopathies.

Purpose: We hypothesized that severe tau burden in brain regions involved in direct or indirect pathways of the basal ganglia correlate with more severe striatal dopamine deficiency in four-repeat (4R) tauopathies. Therefore, we correlated [F]PI-2620 tau-positron-emission-tomography (PET) imaging with [I]-Ioflupane single-photon-emission-computed tomography (SPECT) for dopamine transporter (DaT) availability.

Methods: Thirty-eight patients with clinically diagnosed 4R-tauopathies (21 male; 69.

Validity and value of metabolic connectivity in mouse models of β-amyloid and tauopathy.

Among functional imaging methods, metabolic connectivity (MC) is increasingly used for investigation of regional network changes to examine the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD) or movement disorders. Hitherto, MC was mostly used in clinical studies, but only a few studies demonstrated the usefulness of MC in the rodent brain. The goal of the current work was to analyze and validate metabolic regional network alterations in three different mouse models of neurodegenerative diseases (β-amyloid and tau) by use of 2-deoxy-2-[F]fluoro-d-glucose positron emission tomography (FDG-PET) imaging.

Silicon-Fluoride Acceptors (SiFA) for F-Radiolabeling: From Bench to Bedside.

Fluorine-18 (F) is undoubtedly one of the most frequently applied radionuclides for the development of new radiotracers for positron emission tomography (PET) in the context of clinical cancer, neurological, and metabolic imaging. Until recently, the available radiochemical methodologies to introduce F into organic molecules ranging from small- to medium- and large-sized compounds were limited to a few applicable protocols. With the advent of late-stage fluorination of small aromatic, nonactivated compounds and various noncanonical labeling strategies geared toward the labeling of peptides and proteins, the molecular toolbox for PET radiotracer development was substantially extended.

Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission.

Purpose: Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA).

Methods: FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism.

Individual regional associations between Aβ-, tau- and neurodegeneration (ATN) with microglial activation in patients with primary and secondary tauopathies.

β-amyloid (Aβ) and tau aggregation as well as neuronal injury and atrophy (ATN) are the major hallmarks of Alzheimer's disease (AD), and biomarkers for these hallmarks have been linked to neuroinflammation. However, the detailed regional associations of these biomarkers with microglial activation in individual patients remain to be elucidated. We investigated a cohort of 55 patients with AD and primary tauopathies and 10 healthy controls that underwent TSPO-, Aβ-, tau-, and perfusion-surrogate-PET, as well as structural MRI.

Next-generation PET/CT imaging in meningioma-first clinical experiences using the novel SSTR-targeting peptide [F]SiTATE.

Background: Somatostatin-receptor (SSTR)-targeted PET/CT provides important clinical information in addition to standard imaging in meningioma patients. [F]SiTATE is a novel, F-labeled SSTR-targeting peptide with superior imaging properties according to preliminary data. We provide the first [F]SiTATE PET/CT data of a large cohort of meningioma patients.

Diagnostic performance of PET/CT in the detection of liver metastases in well-differentiated NETs.

Background: The aim of this retrospective study was to compare the diagnostic accuracy of somatostatin receptor (SSR)-PET/CT to liver MRI as reference standard in the evaluation of hepatic involvement in neuroendocrine tumors (NET).

Methods: An institutional database was screened for "SSR" imaging studies between 2006 and 2021. 1000 NET Patients (grade 1/2) with 2383 SSR-PET/CT studies and matching liver MRI in an interval of +3 months were identified.

Validation of the SSTR-RADS 1.0 for the structured interpretation of SSTR-PET/CT and treatment planning in neuroendocrine tumor (NET) patients.

Objectives: The recently proposed standardized reporting and data system for somatostatin receptor (SSTR)-targeted PET/CT SSTR-RADS 1.0 showed promising first results in the assessment of diagnosis and treatment planning with peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET). This study aimed to determine the intra- and interreader agreement of SSTR-RADS 1.

[F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data.

Objectives: Reactive gliosis is a common pathological hallmark of CNS pathology resulting from neurodegeneration and neuroinflammation. In this study we investigate the capability of a novel monoamine oxidase B (MAO-B) PET ligand to monitor reactive astrogliosis in a transgenic mouse model of Alzheimer`s disease (AD). Furthermore, we performed a pilot study in patients with a range of neurodegenerative and neuroinflammatory conditions.

Depletion and activation of microglia impact metabolic connectivity of the mouse brain.

Aim: We aimed to investigate the impact of microglial activity and microglial FDG uptake on metabolic connectivity, since microglial activation states determine FDG-PET alterations. Metabolic connectivity refers to a concept of interacting metabolic brain regions and receives growing interest in approaching complex cerebral metabolic networks in neurodegenerative diseases. However, underlying sources of metabolic connectivity remain to be elucidated.

Comparison of somatostatin receptor expression in patients with neuroendocrine tumours with and without somatostatin analogue treatment imaged with [F]SiTATE.

Purpose: Somatostatin analogues (SSA) are frequently used in the treatment of neuroendocrine tumours. Recently, [F]SiTATE entered the field of somatostatin receptor (SSR) positron emission tomography (PET)/computed tomography (CT) imaging. The purpose of this study was to compare the SSR-expression of differentiated gastroentero-pancreatic neuroendocrine tumours (GEP-NET) measured by [18F]SiTATE-PET/CT in patients with and without previous treatment with long-acting SSAs to evaluate if SSA treatment needs to be paused prior to [18F]SiTATE-PET/CT.

Investigation of image-based lesion and kidney dosimetry protocols for Lu-PSMA-I&T therapy with and without a late SPECT/CT acquisition.

Background: Lu-PSMA therapy has been successfully used to prolong the survival of patients with metastatic castration-resistant prostate cancer. Patient-specific dosimetry based on serial quantitative SPECT/CT imaging can support the understanding of dose-effect relationships. However, multiple SPECT/CT measurements can be challenging for patients, which motivates the investigation of efficient sampling schedules and their impact on dosimetry.

Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer.

Background: Metastatic castration-resistant prostate cancer poses a therapeutic challenge with poor prognosis. The VISION trial showed prolonged progression-free and overall survival in patients treated with lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) radioligand therapy compared with using the standard of care (SoC) alone. The objective of this study was to determine the cost-effectiveness of 177Lu-PSMA-617 treatment compared with SoC therapy.

Biodistribution and dosimetry for combined [Lu]Lu-PSMA-I&T/[Ac]Ac-PSMA-I&T therapy using multi-isotope quantitative SPECT imaging.

Purpose: Quantitative SPECT for patient-specific dosimetry is a valuable tool in the scope of radionuclide therapy, although its clinical application for Ac-based treatments may be limited due to low therapeutic activities. Therefore, the aim of this study was to demonstrate the feasibility of clinical quantitative low-count SPECT imaging during [Lu]Lu-PSMA-I&T/[Ac]Ac-PSMA-I&T treatment.

Methods: Eight prostate cancer patients (1000 MBq/8 MBq [Lu]Lu-PSMA-I&T/[Ac]Ac-PSMA-I&T) received a single-bed quantitative Lu/Ac SPECT/CT acquisition (1 h) at 24 h post treatment (high-energy collimator, 16 projections p.

Assessment of perfusion deficit with early phases of [F]PI-2620 tau-PET versus [F]flutemetamol-amyloid-PET recordings.

Purpose: Characteristic features of amyloid-PET (A), tau-PET (T), and FDG-PET (N) can serve for the A/T/N classification of neurodegenerative diseases. Recent studies showed that the early, perfusion-weighted phases of amyloid- or tau-PET recordings serve to detect cerebrometabolic deficits equally to FDG-PET, therefore providing a surrogate of neuronal injury. As such, two channels of diagnostic information can be obtained in the setting of a single PET scan.

Artificial Intelligence in Oncological Hybrid Imaging.

Background: Artificial intelligence (AI) applications have become increasingly relevant across a broad spectrum of settings in medical imaging. Due to the large amount of imaging data that is generated in oncological hybrid imaging, AI applications are desirable for lesion detection and characterization in primary staging, therapy monitoring, and recurrence detection. Given the rapid developments in machine learning (ML) and deep learning (DL) methods, the role of AI will have significant impact on the imaging workflow and will eventually improve clinical decision making and outcomes.