High Cytotoxic Effect by Combining Copper-64 with a NOTA-Terpyridine Platinum Conjugate.

Terpyridine platinum (TP)-based chemotherapeutic agents target three-dimensional structures on DNA known as G-quadruplexes. We report the rational design and synthesis of a TP conjugate combined with copper-64 (Cu), the decay characteristics of which include emission of β and Auger electrons for radiotherapy and β particles for positron emission tomography (PET) imaging. The present experimental studies show that the novel [Cu]Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-TP is stable, permitting selective killing of cancer cells.

DOI estimation through signal arrival time distribution: a theoretical description including proof of concept measurements.

The challenge to reach 10 ps coincidence time resolution (CTR) in time-of-flight positron emission tomography (TOF-PET) is triggering major efforts worldwide, but timing improvements of scintillation detectors will remain elusive without depth-of-interaction (DOI) correction in long crystals. Nonetheless, this momentum opportunely brings up the prospect of a fully time-based DOI estimation since fast timing signals intrinsically carry DOI information, even with a traditional single-ended readout. Consequently, extracting features of the detected signal time distribution could uncover the spatial origin of the interaction and in return, provide enhancement on the timing precision of detectors.

Performance evaluation of the mouse version of the LabPET II PET scanner.

The LabPET II is a new positron emission tomography technology platform designed to achieve submillimetric spatial resolution imaging using fully pixelated avalanche photodiodes-based detectors and highly integrated parallel front-end processing electronics. The detector was designed as a generic building block to develop devices for preclinical imaging of small to mid-sized animals and for clinical imaging of the human brain. The aim of this work is to assess the physical characteristics and imaging performance of the mouse version of LabPET II scanner following the NEMA NU4-2008 standard and using high resolution phantoms and in vivo imaging applications.

Contribution of perfusion to the C-acetate signal in brown adipose tissue assessed by DCE-MRI and Ga-DOTA PET in a rat model.

Purpose: Determine if dynamic contrast enhanced (DCE) -MRI and/or 68 gallium 1,4,7,10-tetraazacyclododecane N, N', N″, N‴-tretraacetic acid ( Ga-DOTA) positron emission tomography (PET) can assess perfusion in rat brown adipose tissue (BAT). Evaluate changes in perfusion between cold-stimulated and heat-inhibited BAT. Determine if the C-acetate pharmacokinetic model can be constrained with perfusion information to improve assessment of BAT oxidative metabolism.

Cross-Species Physiological Assessment of Brain Estrogen Receptor Expression Using F-FES and F-4FMFES PET Imaging.

Purpose: A retrospective analysis was performed of preclinical and clinical data acquired during the evaluation of the estrogen receptor (ER) PET tracer 4-fluoro-11β-methoxy-16α-[F]-fluoroestradiol (4FMFES) and its comparison with 16α-[F]-fluoroestradiol (FES) in mice, rats, and humans with a focus on the brain uptake.

Procedures: Breast cancer tumor-bearing female BALB/c mice from a previous study and female Sprague-Dawley rats (control and ovariectomized) were imaged by 4FMFES or FES-PET imaging. Immediately after, low-dose CT was performed in the same bed position.

Experimental validation of a coincidence time resolution metric including depth-of-interaction bias for TOF-PET.

Depth-of-interaction (DOI) variability of annihilation photons is known to be a source of coincidence time resolution (CTR) degradation for fast time-of-flight-positron emission tomography detectors. An analytical model was recently proposed to explicitly include the DOI time bias separately from variance-related statistical factors, such as scintillation photon emission and photosensor jitter, in the CTR evaluation. In the present work, an experimental validation of this new model is provided.

A Thermal Model of the LabPET II ASIC.

The LabPET II detection module is the building block of PET scanners for ultra-high-resolution imaging of small to mid-sized animals and the human brain. For optimal performance, it must be operated at a stable temperature. The detection module is composed of four APD-LYSO detector arrays with two flip-chip ASICs mounted on the backside of an interposer generating 550 mW each.

A preclinical PET dual-tracer imaging protocol for ER and HER2 phenotyping in breast cancer xenografts.

Background: Nuclear medicine is on the constant search of precision radiopharmaceutical approaches to improve patient management. Although discordant expression of the estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2) in breast cancer is a known dilemma for appropriate patient management, traditional tumor sampling is often difficult or impractical. While 2-deoxy-2[F]fluoro-D-glucose (F-FDG)-positron emission tomography (PET) is an option to detect subclinical metastases, it does not provide phenotype information.

Fascicle- and Glucose-Specific Deterioration in White Matter Energy Supply in Alzheimer's Disease.

Background: White matter energy supply to oligodendrocytes and the axonal compartment is crucial for normal axonal function. Although gray matter glucose hypometabolism is extensively reported in Alzheimer's disease (AD), glucose and ketones, the brain's two main fuels, are rarely quantified in white matter in AD.

Objective: Using a dual-tracer PET method combined with a fascicle-specific diffusion MRI approach, robust to white matter hyper intensities and crossing fibers, we aimed to quantify both glucose and ketone metabolism in specific white matter fascicles associated with mild cognitive impairment (MCI; n = 51) and AD (n = 13) compared to cognitively healthy age-matched controls (Controls; n = 14).

Promising Performance of 4HMS, a New Zirconium-89 Octadendate Chelator.

Over the last decade, the interest in zirconium-89 (Zr) as a positron-emitting radionuclide increased considerably because of its standardized production and its physical half-life (78.41 h), which matches the biological half-life of antibodies and its successful use in preclinical and clinical applications. So far, desferrioxamine (DFO), a commercially available chelator, has been mainly used as a bifunctional chelating system.

MRI-compatibility study of a PET-insert based on a low-profile detection front-end with submillimeter spatial resolution.

Purpose: The LabPET II detection module is a potential candidate to create an magnetic resonance imaging (MRI) compatible positron emission tomography (PET)-insert with submillimeter spatial resolution for small animal applications. However, the feasibility of such an insert is hampered by the large radial size of the LabPET II front-end electronics and by components containing ferromagnetic materials. In this paper, a new low-profile front-end design based on the LabPET II architecture, called "low-profile detection module," is investigated.

Brain irradiation leads to persistent neuroinflammation and long-term neurocognitive dysfunction in a region-specific manner.

Long-term cognitive deficits are observed after treatment of brain tumors or metastases by radiotherapy. Treatment optimization thus requires a better understanding of the effects of radiotherapy on specific brain regions, according to their sensitivity and interconnectivity. In the present study, behavioral tests supported by immunohistology and magnetic resonance imaging provided a consistent picture of the persistent neurocognitive decline and neuroinflammation after the onset of irradiation-induced necrosis in the right primary somatosensory cortex of Fischer rats.

Metabolism of Exogenous D-Beta-Hydroxybutyrate, an Energy Substrate Avidly Consumed by the Heart and Kidney.

There is growing interest in the metabolism of ketones owing to their reported benefits in neurological and more recently in cardiovascular and renal diseases. As an alternative to a very high fat ketogenic diet, ketones precursors for oral intake are being developed to achieve ketosis without the need for dietary carbohydrate restriction. Here we report that an oral D-beta-hydroxybutyrate (D-BHB) supplement is rapidly absorbed and metabolized in humans and increases blood ketones to millimolar levels.

Automated radiosynthesis of Ga for large-scale routine production using Zn pressed target.

Gallium-68 (Ga) has attracted increasing interest in recent years due to the expanding clinical applications of Ga-based radiopharmaceuticals (Rahbar et al., 2017). Ga is mainly produced via Ge/Ga generators that are limited in yield by the Ge activity (typically up to 1.

Performance investigation of LabPET II detector technology in an MRI-like environment.

The EMI-compatibility of the LabPET II detection module (DM) to develop a high-resolution simultaneous PET/MRI system is investigated. The experimental set-up evaluates the performance of two LabPET II DMs in close proximity to RF coils excited at three different frequencies mimicking the electromagnetic environments of 3 T, 7 T, and 9.4 T MRI scanners.

Performance Simulation of an Ultra-High Resolution Brain PET Scanner Using 1.2-mm Pixel Detectors.

The concept of a new ultra-high resolution positron emission tomography (PET) brain scanner featuring truly pixelated detectors based on the LabPET II technology is presented. The aim of this study is to predict the performance of the scanner using GATE simulations. The NEMA procedures for human and small animal PET scanners were used, whenever appropriate, to simulate spatial resolution, scatter fraction, count rate performance and the sensitivity of the proposed system compared to state-of-the-art PET scanners that would currently be the preferred choices for brain imaging, namely the HRRT dedicated brain PET scanner and the Biograph Vision wholebody clinical PET scanner.

In Vivo Endomicroscopy of Lung Injury and Repair in ARDS: Potential Added Value to Current Imaging.

Background: Standard clinical imaging of the acute respiratory distress syndrome (ARDS) lung lacks resolution and offers limited possibilities in the exploration of the structure-function relationship, and therefore cannot provide an early and clear discrimination of patients with unexpected diagnosis and unrepair profile. The current gold standard is open lung biopsy (OLB). However, despite being able to reveal precise information about the tissue collected, OLB cannot provide real-time information on treatment response and is accompanied with a complication risk rate up to 25%, making longitudinal monitoring a dangerous endeavor.

A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment.

Introduction: Unlike for glucose, uptake of the brain's main alternative fuel, ketones, remains normal in mild cognitive impairment (MCI). Ketogenic medium chain triglycerides (kMCTs) could improve cognition in MCI by providing the brain with more fuel.

Methods: Fifty-two subjects with MCI were blindly randomized to 30 g/day of kMCT or matching placebo.

Intratumoral F-FLT infusion in metabolic targeted radiotherapy.

Background: The goal of targeted radiotherapy (TRT) is to administer radionuclides to tumor cells, while limiting radiation exposure to normal tissues. 3'-Deoxy-3'-[F]-fluorothymidine (F-FLT) is able to target tumor cells and emits a positron with energy appropriate for local (~ 1 mm range) radiotherapy. In the present work, we investigated the potential of TRT with a local administration of F-FLT alone or in combination with 5-fluorouracil (5FU), which acts as a chemotherapeutic agent and radiosensitizer.

Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up.

We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline ( = 25) and two ( = 25) and four ( = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (K) declined by 6%-12% mainly in the temporo-parietal lobes and cingulate gyri ( ≤ 0.

Topological principles and developmental algorithms might refine diffusion tractography.

The identification and reconstruction of axonal pathways in the living brain or "ex-vivo" is promising a revolution in connectivity studies bridging the gap from animal to human neuroanatomy with extensions to brain structural-functional correlates. Unfortunately, the methods suffer from juvenile drawbacks. In this perspective paper we mention several computational and developmental principles, which might stimulate a new generation of algorithms and a discussion bridging the neuroimaging and neuroanatomy communities.

Mouse Mast Cell Protease 4 Deletion Protects Heart Function and Survival After Permanent Myocardial Infarction.

Chymase, a mast cell serine protease involved in the generation of multiple cardiovascular factors, such as angiotensin II and endothelin-1 (ET-1), is elevated and participates in tissue degeneration after permanent myocardial infarction (PMI). Anesthetized 4-month old male wild-type (WT) C57BL/6J mice and mouse mast cell protease-4 knockout (mMCP-4 KO) congeners were subjected to ligation of the left anterior descending (LAD) coronary artery. A group of mice was then subjected to Kaplan-Meier 28-day survival analysis.

Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting.

Antibody-conjugates (ACs) modified with virus-derived peptides are a potentially powerful class of tumor cell delivery agents for molecular payloads used in cancer treatment and imaging due to increased cellular accumulation over current ACs. During early AC in vitro development, fluorescence techniques and radioimmunoassays are sufficient for determining intracellular localization, accumulation efficiency, and target cell specificity. Currently, there is no consensus on standardized methods for preparing cells for evaluating AC intracellular accumulation and localization.

Robust high-yield ~1 TBq production of cyclotron based sodium [Tc]pertechnetate.

Unlabelled: This paper presents the irradiation and processing of high-current Mo targets at the University of Alberta (UofA) in a GMP compliant setting. For purpose of comparison with a second production facility, additional studies at Centre Hospitalier Universitaire de Sherbrooke (CHUS) are also described.

Introduction: More than 70% of today's diagnostic radiopharmaceuticals are based on Tc, however the conventional supply chain for obtaining Tc is fragile.