Safety observations in neuroblastoma patients undergoing 18F-mFBG PET.

Objective: Limited safety data have been published on fluorine-18 (18F) meta-fluorobenzylguanidine (mFBG), a new PET radiopharmaceutical for imaging neural crest and neuroendocrine tumors. As part of a prospective clinical trial, safety data in patients with neuroblastoma were collected and analyzed.

Methods: Between April 2015 and January 2022, 27 patients with neuroblastoma underwent 18F-mFBG PET imaging as part of an ongoing single-center phase 1/2 trial (NCT02348749).

Positron Emission Tomography reveals age-associated hypothalamic microglial activation in women.

In rodents, hypothalamic inflammation plays a critical role in aging and age-related diseases. Hypothalamic inflammation has not previously been assessed in vivo in humans. We used Positron Emission Tomography (PET) with a radiotracer sensitive to the translocator protein (TSPO) expressed by activated microglia, to assess correlations between age and regional brain TSPO in a group of healthy subjects (n = 43, 19 female, aged 23-78), focusing on hypothalamus.

Decreased CSF clearance and increased brain amyloid in Alzheimer's disease.

Background: In sporadic Alzheimer's disease (AD), brain amyloid-beta (Aβ) deposition is believed to be a consequence of impaired Aβ clearance, but this relationship is not well established in living humans. CSF clearance, a major feature of brain glymphatic clearance (BGC), has been shown to be abnormal in AD murine models. MRI phase contrast and intrathecally delivered contrast studies have reported reduced CSF flow in AD.

Population-based input function for TSPO quantification and kinetic modeling with [C]-DPA-713.

Introduction: Quantitative positron emission tomography (PET) studies of neurodegenerative diseases typically require the measurement of arterial input functions (AIF), an invasive and risky procedure. This study aims to assess the reproducibility of [C]DPA-713 PET kinetic analysis using population-based input function (PBIF). The final goal is to possibly eliminate the need for AIF.

Intrathecal Tc-DTPA imaging of molecular passage from lumbar cerebrospinal fluid to brain and periphery in humans.

Introduction: Cerebrospinal fluid (CSF) molecular exchange with brain interstitial fluid (ISF) and periphery is implicated in neurological disorders but needs better quantitative clinical assessment approaches.

Methods: Following intrathecal (ITH) dosing via lumbar puncture, Technetium-99 m (Tc-) diethylenetriaminepentaacetic acid (DTPA) imaging was used to quantify neuraxial spread, CSF-brain molecular exchange, and CSF-peripheral clearance in 15 normal human volunteers. The effect of experimental convection manipulation on these processes was also assessed.

Neurophysiological Biomarkers of Parkinson's Disease.

Background: There is a need for reliable and robust Parkinson's disease biomarkers that reflect severity and are sensitive to disease modifying investigational therapeutics.

Objective: To demonstrate the utility of EEG as a reliable, quantitative biomarker with potential as a pharmacodynamic endpoint for use in clinical assessments of neuroprotective therapeutics for Parkison's disease.

Methods: A multi modal study was performed including aquisition of resting state EEG data and dopamine transporter PET imaging from Parkinson's disease patients off medication and compared against age-matched controls.

Statistical Considerations for Planning Clinical Trials with Quantitative Imaging Biomarkers.

As imaging technologies and treatment options continue to advance, imaging outcome measures are becoming increasingly utilized as the basis of making major decisions in new drug development and clinical practice. Quantitative imaging biomarkers (QIBs) are now commonly used for subject selection, response assessment, and safety monitoring. Although quantitative measurements can have many advantages compared with subjective, qualitative endpoints, it is important to recognize that QIBs are measured with error.

18F-FPEB PET/CT Shows mGluR5 Upregulation in Parkinson's Disease.

Background And Purpose: Dopamine and glutamate reciprocally regulate each other in some of the neurocircuits affected by Parkinson's disease (PD). The objective of this pilot study was to explore relationships between these neurotransmitter systems with positron emission tomography.

Methods: The sample consisted of nine patients with PD and eight healthy volunteers (HVs).

Noninvasive PK11195-PET Image Analysis Techniques Can Detect Abnormal Cerebral Microglial Activation in Parkinson's Disease.

Background And Purpose: Neuroinflammation has been implicated in the pathophysiology of Parkinson's disease (PD), which might be influenced by successful neuroprotective drugs. The uptake of [ C](R)-PK11195 (PK) is often considered to be a proxy for neuroinflammation, and can be quantified using the Logan graphical method with an image-derived blood input function, or the Logan reference tissue model using automated reference region extraction. The purposes of this study were (1) to assess whether these noninvasive image analysis methods can discriminate between patients with PD and healthy volunteers (HVs), and (2) to establish the effect size that would be required to distinguish true drug-induced changes from system variance in longitudinal trials.

[ C]arachidonic acid incorporation measurement in human brain: Optimization for clinical use.

Arachidonic acid (AA) is involved in signal transduction, neuroinflammation, and production of eicosanoid metabolites. The AA brain incorporation coefficient (K*) is quantifiable in vivo using [ C]AA positron emission tomography, although repeatability remains undetermined. We evaluated K* estimates obtained with population-based metabolite correction (PBMC) and image-derived input function (IDIF) in comparison to arterial blood-based estimates, and compared repeatability.

Reduction of PK11195 uptake observed in multiple sclerosis lesions after natalizumab initiation.

Objective: The objective of this study is to longitudinally analyze the uptake of [C]PK11195-PET in multiple sclerosis patients after 3 and 6 months of natalizumab treatment.

Methods: Eighteen MS patients, starting treatment with monocloncal anti-VLA-4, were enrolled in a longitudinal PK-PET study. PK uptake was quantified by volume of distribution (VT) calculation using image-derived input function at baseline, 3 and 6 months.

Three-Dimensional Dosimetry for Radiation Safety Estimates from Intrathecal Administration.

Intrathecal administration is of growing interest for drug delivery, and its utility is being increasingly investigated through imaging. In this work, the 3-dimensional Voxel-Based Internal Dosimetry Application (VIDA) and 4D Extended Cardiac Torso Phantom (XCAT) were extended to provide radiation safety estimates specific to intrathecal administration. The 3-dimensional VIDA dosimetry application Monte Carlo simulation was run using a modified XCAT phantom with additional and edited cerebrospinal fluid (CSF) regions to produce voxel-level absorbed dose per unit cumulated activity maps for 9 selected source regions.

Automated segmentation of MR imaging to determine normative central nervous system cerebrospinal fluid volumes in healthy volunteers.

An accurate non-invasive method to determine total body cerebrospinal fluid volume has a number of potential diagnostic and therapeutic applications. Herein we describe a technique for automated segmentation of total body MRI data to determine cranial and spinal CSF volume in 15 healthy adults. These in vivo estimates of CSF volume exceed the standard reported volume of 150mL in human adults and provide normative data for diagnosis of disease states such as hydrocephalus and therapy including pharmacologic dosimetry.

Yttrium-90 microsphere radioembolotherapy in a patient with spontaneously ruptured hepatocellular carcinoma.

Spontaneous rupture of hepatocellular carcinoma (HCC) is a potentially fatal presentation of the disease. Although many options for treatment exist, Yttrium-90 transcatheter arterial radioembolization has not previously been reported. We report a case of a 92-year-old woman found to have a ruptured HCC treated with radioembolization that showed no viable tumor and no extrahepatic disease at 2 years.

Repeatability of 18F-FDG PET/CT in Advanced Non-Small Cell Lung Cancer: Prospective Assessment in 2 Multicenter Trials.

Unlabelled: PET/CT with the glucose analog (18)F-FDG has several potential applications for monitoring tumor response to therapy in patients with non-small cell lung cancer (NSCLC). A prerequisite for many of these applications is detailed knowledge of the repeatability of quantitative parameters derived from (18)F-FDG PET/CT studies.

Methods: The repeatability of the (18)F-FDG signal was evaluated in 2 prospective multicenter trials.

Cortical laminar binding of PET amyloid and tau tracers in Alzheimer disease.

Unlabelled: Neurofibrillary tau pathology and amyloid β (Aβ) plaques, characteristic lesions of Alzheimer disease (AD), show different neocortical laminar distributions. Neurofibrillary-tangle tau pathology tends to be closer to the gray matter-white matter boundary, whereas Aβ is dispersed throughout the width of the cortical ribbon.

Methods: Using PET radiotracers for tau and Aβ lesions, we developed an image analysis tool to measure the distance of tracer-positive voxels from the gray matter-white matter boundary.

Variability in assessing treatment response: metastatic colorectal cancer as a paradigm.

Purpose: The cutoff values currently used to categorize tumor response to therapy are neither biologically based nor tailored for measurement reproducibility with contemporary imaging modalities. Sources and magnitudes of discordance in response assessment in metastatic colorectal cancer (mCRC) are unknown.

Experimental Design: A subset of patients' CT images of chest, abdomen, and pelvis were randomly chosen from a multicenter clinical trial evaluating insulin-like growth factor receptor type 1-targeted therapy in mCRC.

Repeatability of quantitative FDG-PET/CT and contrast-enhanced CT in recurrent ovarian carcinoma: test-retest measurements for tumor FDG uptake, diameter, and volume.

Purpose: Repeatability of baseline FDG-PET/CT measurements has not been tested in ovarian cancer. This dual-center, prospective study assessed variation in tumor 2[18F]fluoro-2-deoxy-D-glucose (FDG) uptake, tumor diameter, and tumor volume from sequential FDG-PET/CT and contrast-enhanced computed tomography (CECT) in patients with recurrent platinum-sensitive ovarian cancer.

Experimental Design: Patients underwent two pretreatment baseline FDG-PET/CT (n = 21) and CECT (n = 20) at two clinical sites with different PET/CT instruments.

(11)C-MK-8278 PET as a tool for pharmacodynamic brain occupancy of histamine 3 receptor inverse agonists.

Unlabelled: The histamine 3 (H3) receptor is a presynaptic autoreceptor in the central nervous system that regulates the synthesis and release of histamine and modulates the release of other major neurotransmitters. H3 receptor inverse agonists (IAs) may be efficacious in the treatment of various central nervous system disorders, including excessive daytime sleepiness, attention deficit hyperactivity disorder, Alzheimer disease, ethanol addiction, and obesity.

Methods: Using PET and a novel high-affinity and selective radioligand (11)C-MK-8278, we studied the tracer biodistribution, quantification, and brain H3 receptor occupancy (RO) of MK-0249 and MK-3134, 2 potential IA drugs targeting cerebral H3 receptors, in 6 healthy male subjects (age, 19-40 y).

18F-FPEB, a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors: a first-in-human study of radiochemical safety, biokinetics, and radiation dosimetry.

Unlabelled: Identification of safe and valid PET radioligands for metabotropic glutamate receptor, type 5 (mGluR5), is essential to measure changes in brain mGluR5 in neuropsychiatric disorders, to confirm central mGluR5 occupancy of drug candidates, and to guide dose selection for obtaining an optimum therapeutic window. Here we present the results of a first-in-human study assessing the safety and effectiveness of a novel PET radiopharmaceutical, (18)F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ((18)F-FPEB), for quantifying regional brain concentrations of mGluR5.

Methods: Quantification of whole-body biokinetics was conducted in 6 healthy adults (3 men and 3 women).

Measurement of tumor volumes improves RECIST-based response assessments in advanced lung cancer.

Objective: This study was designed to characterize the reproducibility of measurement for tumor volumes and their longest tumor diameters (LDs) and estimate the potential impact of using changes in tumor volumes instead of LDs as the basis for response assessments.

Methods: We studied patients with advanced lung cancer who have been observed longitudinally with x-ray computed tomography in a multinational trial. A total of 71 time points from 10 patients with 13 morphologically complex target lesions were analyzed.