FAPI PET/CT for tracking disease trajectory in myositis-related interstitial lung disease.

Background: Interstitial lung disease (ILD) is associated with morbidity and mortality in idiopathic inflammatory myopathies (IIM). Predicting ILD progression remains a significant challenge, as conventional diagnostic tools such as pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) have limited prognostic accuracy. This study evaluated whether Ga-labelled inhibitor of Fibroblast-Activation-Protein (FAPI) based PET/CT at baseline predicts ILD evolution over two years.

Does PARP1 up-regulation correlate with PSMA expression in patients with metastatic castration-resistant prostate cancer studied with [F]PARPi and [Ga]PSMA PET/CT?

Purpose: [F] Poly-ADP-ribose polymerase inhibitors (PARPi), a novel radiotracer, enables visualization of PARP1 upregulation by PET imaging. Here, we aimed to quantify PARPi uptake in tumor lesions of metastatic castration-resistant PCa (mCRPC) patients and perform a comparison with prostate specific membrane antigen (PSMA) expression using PET/CT scans.

Methods: Data from 22 male patients with mCRPC, who underwent [F]PARPi and [Ga]Ga-PSMA-11 PET/CT scans, were retrospectively quantified.

Phenotyping extracellular vesicles and their serotonin transporter cargo in major depressive disorder.

With their ability to cross the blood-brain barrier, transport and regulate the release of various signaling molecules, extracellular vesicles (EVs) constitute a novel avenue to study intercellular communication in various pathologies, including psychiatric disorders. We studied 34 major depressive disorder (MDD) patients and 57 healthy controls and characterized EVs isolated from plasma using digital holographic tomography (DHT) and nanoparticle tracking analysis (NTA). EVs detected in DHT were markedly smaller and less variable in size in MDD patients.

A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing.

Considering the complexity of serotonergic influence on emotions, we conducted a comprehensive investigation of the interplay between emotion processing and the serotonergic system using simultaneous functional and molecular neuroimaging during pharmacological challenge while disentangling the effects of serotonin transporter (SERT) binding, genotype, and diagnosis of major depressive disorder (MDD). Herein, 153 subjects (44 with MDD) performed a facial emotion processing task during functional magnetic resonance imaging (fMRI) before and after an acute intravenous application of 8 mg citalopram or placebo. Patients with MDD were assessed again after at least three months of antidepressant treatment.

Efficacy, Safety, Blood Kinetics, and Bi Distribution Studies of [Ac]Ac-SibuDAB in Prostate Cancer Patients.

Ac-labeled ()-ibuprofen-diaminobutyric acid-PSMA (SibuDAB) is a novel, albumin-binding compound in prostate-specific membrane antigen (PSMA)-targeted α-therapy of prostate cancer. It showed superior preclinical efficacy results to [Ac]Ac-PSMA-617. Ac decays via multiple α-particle emissions.

In vivo serotonin 1A receptor distribution in treatment-resistant depression.

Major depressive disorder (MDD) ranks among the leading causes of disability worldwide. An additional burden arises from treatment-resistance, defined by a lack of response to two or more adequate pharmacotherapeutic treatment trials. Unlike in MDD, where the serotonin 1A receptor subtype (5-HT) has commonly been used to study pathophysiological alterations, treatment-resistant depression (TRD) subjects represent a less investigated cohort.

Connecting the dots: approaching a standardized nomenclature for molecular connectivity in positron emission tomography.

Positron emission tomography (PET)-based connectivity analysis provides a molecular perspective that complements fMRI-derived functional connectivity. However, lack of standardized terminology and diverse methodologies in PET connectivity studies has resulted in inconsistencies, complicating the interpretation and comparison of results across studies. A standardized nomenclature is thus needed to reduce ambiguity, enhance reproducibility, and facilitate interpretability across radiotracers, imaging modalities and studies.

Adaptation of a commercially available module for the production of alpha-[C]methyl-L-tryptophan ([C]AMT) for human use.

The complex radiosynthesis of alpha-[C]methyl-L-tryptophan ([C]AMT) involves harsh chemicals and conditions, posing challenges for its implementation on commercially available synthesis modules. This study describes the adaptation of the GE TRACERlab FX2 C module for [C]AMT production using both a half-manual approach and a semi-automated method incorporating a 16-way valve system. [C]AMT was synthesized with decay-corrected radiochemical yields of 13 ± 7.

A direct effect of the hematocrit on blood glucose: Evidence from hypoxia- and erythropoietin-treated mice.

Blood glucose is lower in mountain dwellers living under low partial oxygen pressure. We show that obese mice maintained under hypoxia exhibit a delayed but distinct decrease in blood glucose with improved insulin sensitivity, which is independent of changes in body weight. This effect of hypoxia is mediated by erythropoiesis and is a direct result of the rising hematocrit, which could be due to erythrocytes acting as carriers of glucose units in the blood.

Optimal filtering strategies for task-specific functional PET imaging.

Functional Positron Emission Tomography (fPET) is an effective tool for studying dynamic processes in glucose metabolism and neurotransmitter action, providing insights into brain function and disease progression. However, optimizing signal processing to extract stimulation-specific information remains challenging. This study systematically evaluates state-of-the-art filtering techniques for fPET imaging.

Effect of probenecid on the whole-body disposition of 6-bromo-7-[C]methylpurine in humans assessed with long axial field-of-view PET/CT.

Purpose: Multidrug resistance-associated proteins (MRPs) have a widespread tissue distribution. They play an important role in drug disposition and drug-drug interactions (DDIs) and have been associated with various diseases. PET with 6-bromo-7-[C]methylpurine ([C]BMP) has been used to assess MRP1 function in the brain and lungs of mice.

[C]Metoclopramide PET can detect a seizure-induced up-regulation of cerebral P-glycoprotein in epilepsy patients.

Background: P-glycoprotein (P-gp) is an efflux transporter which is abundantly expressed at the blood-brain barrier (BBB) and which has been implicated in the pathophysiology of various brain diseases. The radiolabelled antiemetic drug [C]metoclopramide is a P-gp substrate for positron emission tomography (PET) imaging of P-gp function at the BBB. To assess whether [C]metoclopramide can detect increased P-gp function in the human brain, we employed drug-resistant temporal lobe epilepsy (TLE) as a model disease with a well characterised, regional P-gp up-regulation at the BBB.

Dynamics of human serotonin synthesis differentially link to reward anticipation and feedback.

Serotonin (5-HT) plays an essential role in reward processing, however, the possibilities to investigate 5-HT action in humans during emotional stimulation are particularly limited. Here we demonstrate the feasibility of assessing reward-specific dynamics in 5-HT synthesis using functional PET (fPET), combining its molecular specificity with the high temporal resolution of blood oxygen level dependent (BOLD) fMRI. Sixteen healthy volunteers underwent simultaneous fPET/fMRI with the radioligand [C]AMT, a substrate for tryptophan hydroxylase.

In vivo assessment of safety, biodistribution, and radiation dosimetry of the [F]Me4FDG PET-radiotracer in adults.

Background: Approaches targeting the sodium-glucose cotransporter (SGLT) could represent a promising future therapeutic strategy for numerous oncological and metabolic diseases. In this study, we evaluated the safety, biodistribution and radiation dosimetry of the glucose analogue positron emission tomography (PET) agent [F] labeled alpha-methyl-4-deoxy-4-[F]fluoro-D-glucopyranoside ([F]Me4FDG) with high sodium-glucose cotransporter and low glucose transporter (GLUT) affinity. For this purpose, five healthy volunteers (1 man, 4 women) underwent multiple whole-body PET/computed tomography (CT) examinations starting with injection and up to 4 h after injection of averaged (2.

St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.

St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs.

Advancing 6-bromo-7-[C]methylpurine to clinical use: improved regioselective radiosynthesis, non-clinical toxicity data and human dosimetry estimates.

Background: 6-Bromo-7-[C]methylpurine ([C]BMP) is a radiotracer for positron emission tomography (PET) to measure multidrug resistance-associated protein 1 (MRP1) transport activity in different tissues. Previously reported radiosyntheses of [C]BMP afforded a mixture of 7- and 9-[C]methyl regioisomers. To prepare for clinical use, we here report an improved regioselective radiosynthesis of [C]BMP, the results of a non-clinical toxicity study as well as human dosimetry estimates based on mouse PET data.

Assessment of PSMA Expression of Healthy Organs in Different Stages of Prostate Cancer Using [Ga]Ga-PSMA-11-PET Examinations.

The efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is currently being investigated for its application in patients with early-stage prostate cancer (PCa). However, little is known about PSMA expression in healthy organs in this cohort. Collectively, 202 [Ga]Ga-PSMA-11 positron emission tomography (PET) scans from 152 patients were studied.

A Fully Automated Synthesis of 14-()-[F]fluoro-6-thia-heptadecanoic Acid ([F]FTHA) on the Elixys Radiosynthesizer.

14-()-[F]fluoro-6-thia-heptadecanoic acid ([F]FTHA) is a radiocompound for imaging the fatty acid circulation by positron emission tomography. A revived interest in imaging of lipid metabolism led us to a constant tracer production over three years, initially using a conventional vessel-based synthesizer and later transitioning to the cassette-based Elixys synthesizer. On the Elixys module, the radiochemical yield of [F]FTHA could be increased by more than two times, reaching 13.

Quality Assurance Investigations and Impurity Characterization during Upscaling of [Lu]Lu-PSMA.

[Lu]Lu-PSMA is widely used for the radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC). Since this kind of therapy has gained a large momentum in recent years, an upscaled production process yielding multiple patient doses in one batch has been developed. During upscaling, the established production method as well as the HPLC quality control were challenged.

High-temporal resolution functional PET/MRI reveals coupling between human metabolic and hemodynamic brain response.

Purpose: Positron emission tomography (PET) provides precise molecular information on physiological processes, but its low temporal resolution is a major obstacle. Consequently, we characterized the metabolic response of the human brain to working memory performance using an optimized functional PET (fPET) framework at a temporal resolution of 3 s.

Methods: Thirty-five healthy volunteers underwent fPET with [F]FDG bolus plus constant infusion, 19 of those at a hybrid PET/MRI scanner.

Impact of genetic variants within serotonin turnover enzymes on human cerebral monoamine oxidase A in vivo.

Variants within the monoamine oxidase A (MAO-A, MAOA) and tryptophan hydroxylase 2 (TPH2) genes, the main enzymes in cerebral serotonin (5-HT) turnover, affect risk for depression. Depressed cohorts show increased cerebral MAO-A in positron emission tomography (PET) studies. TPH2 polymorphisms might also influence brain MAO-A because availability of substrates (i.