Molecular Imaging Techniques Research Articles

Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941.

Positron emission tomography (PET) is an essential molecular imaging technique providing insights into pathways and using specific targeted radioligands for in vivo investigations. Within this protocol, a robust and reliable remote-controlled radiosynthesis of [11C]SNAP-7941, an antagonist to the melanin-concentrating hormone receptor 1, is described. The radiosynthesis starts with cyclotron produced [11C]CO2 that is subsequently further reacted via a gas-phase transition to [11C]CH3OTf. Then, this reactive intermediate is introduced to the precursor solution and forms the respective radiotracer. Chemical as well as the radiochemical purity are determined by means of RP-HPLC, routinely implemented in the radiopharmaceutical quality control process. Additionally, the molar activity is calculated as it is a necessity for the following real-time kinetic investigations. Furthermore, [11C]SNAP-7941 is applied to MDCKII-WT and MDCKII-hMDR1 cells for evaluating the impact of P-glycoprotein (P-gp) expression on cell accumulation. For this reason, the P-gp expressing cell line (MDCKII-hMDR1) is either used without or with blocking prior to experiments by means of the P-gp substrate (±)-verapamil and the results are compared to the ones observed for the wildtype cells. The overall experimental approach demonstrates the importance of a precise time-management that is essential for every preclinical and clinical study using PET tracers radiolabelled with short-lived nuclides, such as carbon-11 (half-life: 20 min).

Emulsion Techniques for the Production of Pharmacological Nanoparticles.

Nanoparticles have the advantages over micron-sized particles to typically provide higher intracellular uptake and drug bioavailability. Emulsion techniques are commonly used methods for producing nanoparticles aiming at high encapsulation efficiency, high stability, and low toxicity. Here, the recent developments of nanoparticles prepared from emulsions, the synthesis of nanoparticles, their physicochemical properties, and their biomedical applications are discussed. Selection of techniques, such as emulsion polymerization, miniemulsion polymerization, microemulsion polymerization, and emulsion-solvent evaporation processes, strongly influences morphologies, size distributions, and particle properties. Details in the synthetic strategies governing the performance of nanoparticles in bioimaging, biosensing, and drug delivery are presented. Benefits and limitations of molecular imaging techniques are also discussed.

Application of advanced brain positron emission tomography–based molecular imaging for a biological framework in neurodegenerative proteinopathies

IntroductionA rapid transition from a clinical-based classification to a pathology-based classification of neurodegenerative conditions, largely promoted by the increasing availability of imaging biomarkers, is emerging. The Framework for Innovative Multi-tracer molecular Brain Imaging, funded by the EU Joint Program - Neurodegenerative Disease Research 2016 “Working Groups for Harmonisation and Alignment in Brain Imaging Methods for Neurodegeneration,” aimed at providing a roadmap for the applications of established and new molecular imaging techniques in dementia. MethodsWe consider current and future implications of adopting a pathology-based framework for the use and development of positron emission tomography techniques. ResultsThis approach will enhance efforts to understand the multifactorial etiology of Alzheimer's disease and other dementias. DiscussionThe availability of pathology biomarkers will soon transform clinical and research practice. Crucially, a comprehensive understanding of strengths and caveats of these techniques will promote an informed use to take full advantage of these tools.

Optimisation of secondary ion transport in ambient pressure MeV SIMS

Ambient Pressure MeV SIMS (AP MeV SIMS) is a special application of MeV SIMS technique for molecular detection and imaging under ambient conditions. There are several advantages of using ambient over non-ambient techniques such as minimising or completely avoiding sample preparation that can contribute to the reducing of costs and shortening of analysis. Moreover, by performing analysis in ambient conditions negative vacuum influence on samples will be avoided. The emergence of ambient mass spectrometry techniques over the past decade has been enormous with a broad range of applications such as food quality, environmental analysis and life sciences [1,2]. On the other hand, the disadvantage of ambient pressure mass spectrometry techniques is the influence of the ambient background which can suppress the signal from the target. In AP MeV SIMS, molecular species present in ambient surrounding of the sampling site will also be ionised by ion beams hence secondary ions originating from the sample have to be transported in the most efficient manner from the site of interaction of ion beams and target into the mass spectrometer capillary and, finally, into the mass spectrometer [3]. In this work, we present the optimisation of the mass spectrometer capillary temperature, distances of mass spectrometer and sheath gas, in our case helium, with respect to the beam axis and angle of the helium flow capillary with respect to the sample.

MP60-15 USE OF INTRAOPERATIVE 68 GALLIUM-PSMA CERENKOV LUMINESCENCE IMAGING FOR SURGICAL MARGINS IN RADICAL PROSTATECTOMY – A FEASIBILITY STUDY

INTRODUCTION AND OBJECTIVES:Cerenkov Luminescence Imaging (CLI) is a molecular imaging technique that detects light emitted by Positron Emission Tomography (PET) radiopharmaceuticals.This first-in-...

What proportion of striatal D2 receptors are occupied by endogenous dopamine at baseline? A meta-analysis with implications for understanding antipsychotic occupancy

Using molecular imaging techniques – positron emission tomography (PET) and single-photon emission computed tomography (SPECT) – in conjunction with an acute dopamine depletion challenge (alpha-methyl-para-tyrosine) it is possible to estimate endogenous dopamine levels occupying striatal dopamine D2 receptors (D2R) in humans in vivo. However, it is unclear what proportion of striatal D2R are occupied by endogenous dopamine under normal conditions. This is important since it has been suggested that in schizophrenia there may be a substantial proportion of striatal D2R which are occupied by endogenous dopamine and not accessible by therapeutic doses of antipsychotics. In order to clarify these issues, we conducted a meta-analysis of dopamine depletion studies using substituted benzamide radiotracers in healthy persons. This meta-analysis suggests that anywhere from 8 to 21% (weighted average 11%) of striatal D2R may be occupied by endogenous dopamine at baseline. Using these estimates, we propose an updated occupancy model and tentatively suggest that antipsychotics inhibit a smaller proportion of the total pool of striatal D2R in vivo than previously acknowledged.This article is part of the issue entitled ‘Special Issue on Antipsychotics’.

Molecular Imaging of Renal Malignancy: A Review

Renal cell carcinoma (RCC) is a common malignancy that is often detected incidentally in patients undergoing cross-sectional imaging of the abdomen for workup of pain or other symptoms. Due to overlap in imaging findings of RCC and benign tumors, biopsy may be necessary to confirm the diagnosis. Biopsies are occasionally non-diagnostic, however, and in small lesions or patients with comorbidities may not be technically feasible. Molecular imaging techniques can characterize tumors as being more likely malignant or benign and obviate the need for invasive testing, as well as providing accurate whole-body staging in patients with known RCC. PET/CT with 18F-FDG and other radionuclides can identify primary renal masses with higher malignant potential and also allows for sensitive detection of metastatic RCC. SPECT/CT imaging with 99mTc-sestamibi can provide useful information to support the diagnosis of benign oncocytic neoplasms over more aggressive RCC subtypes. Investigational molecular imaging techniques such as immunoPET and hyperpolarized 13C MRI have also shown promise in renal mass characterization. This review article aims to outline the various molecular imaging modalities available in the evaluation of primary renal tumors and in whole-body staging of metastatic RCC.

Dynamic Imaging of Glucose and Lactate Metabolism by 13C-MRS without Hyperpolarization

Metabolic reprogramming is one of the defining features of cancer and abnormal metabolism is associated with many other pathologies. Molecular imaging techniques capable of detecting such changes have become essential for cancer diagnosis, treatment planning, and surveillance. In particular, 18F-FDG (fluorodeoxyglucose) PET has emerged as an essential imaging modality for cancer because of its unique ability to detect a disturbed molecular pathway through measurements of glucose uptake. However, FDG-PET has limitations that restrict its usefulness in certain situations and the information gained is limited to glucose uptake only.13C magnetic resonance spectroscopy theoretically has certain advantages over FDG-PET, but its inherent low sensitivity has restricted its use mostly to single voxel measurements unless dissolution dynamic nuclear polarization (dDNP) is used to increase the signal, which brings additional complications for clinical use. We show here a new method of imaging glucose metabolism in vivo by MRI chemical shift imaging (CSI) experiments that relies on a simple, but robust and efficient, post-processing procedure by the higher dimensional analog of singular value decomposition, tensor decomposition. Using this procedure, we achieve an order of magnitude increase in signal to noise in both dDNP and non-hyperpolarized non-localized experiments without sacrificing accuracy. In CSI experiments an approximately 30-fold increase was observed, enough that the glucose to lactate conversion indicative of the Warburg effect can be imaged without hyper-polarization with a time resolution of 12s and an overall spatial resolution that compares favorably to 18F-FDG PET.

In the future, emission‐guided radiation therapy will play a critical role in clinical radiation oncology

Emission‐guided radiation therapy entails the use of radiation emitted by molecular imaging probes (SPECT for PET) to guide delivery directly, thus avoiding the need to wait for long acquisition times to collect sufficient count statistics. The potential of biological targeting in radiation treatment planning, taking advantage of advanced molecular imaging techniques in the form of hybrid SPECT/CT, PET/CT, or PET/MRI systems, is well established. The last three decades have witnessed abundant contributions indicative of the advantages of multiparametric molecular imaging in this framework. Ultimately, molecular imaging‐guided radiation therapy planning holds the promise of improved delineation of target volumes even in the presence of significant motion. Yet, despite significant advances to date, challenges remain limiting exploitation of the potential of this technology in the clinic to academic facilities with advanced technical support. Fortunately, these limitations are not preventing novel exciting developments to emerge with the aim to further boost the incorporation of multimodality imaging in the process of radiation therapy planning for various indications. In this regard, the conceptual basis of using on‐board PET to guide the radiation treatment process has been around since 2010. A small company based in the US (RefleXion Medical, Hayward, CA) pioneered the development of a device enabling commercial implementation of one approach to biologically guided radiation therapy. The product was displayed for the first time at the last ASTRO 2018 annual meeting. While some think that this is relevant technology that should soon be adopted for use in the clinic, others think that the concept is still in its infancy and not mature enough for clinical adoption. This is the topic addressed in this month's Point/Counterpoint debate.

Auxiliary role of D5 dopamine receptor as a marker in paranoid schizophrenia patients

ABSTRACTOBJECTIVE: Schizophrenia, commonly develops in adolescents and young adults and Paranoid is the most common type. Newly progress in molecular biology and imaging techniques has enabled new ...

The Potential of Photoacoustic Techniques for Molecular Imaging.

The Potential of Photoacoustic Techniques for Molecular Imaging.

High resolution crossed molecular beams study of the H+HD→H2+D reaction

The H+H2 reaction is the simplest chemical reaction system and has long been the prototype model in the study of reaction dynamics. Here we report a high resolution experimental investigation of the state-to-state reaction dynamics in the H+HD→H2+D reaction by using the crossed molecular beams method and velocity map ion imaging technique at the collision energy of 1.17 eV. D atom products in this reaction were probed by the near threshold 1+1′ (vacuum ultraviolet+ultraviolet) laser ionization scheme. The ion image with both high angular and energy resolution were acquired. State-to-state differential cross sections was accurately derived. Fast forward scattering oscillations, relating with interference effects in the scattering process, were clearly observed for H2 products at H2(v′=0, j′=1) and H2(v′=0, j′=3) rovibrational levels. This study further demonstrates the importance of measuring high-resolution differential cross sections in the study of state-to-state reaction dynamics in the gas phase.

The diagnostic framework for screening Alzheimer's disease in the Chinese population

Criteria for diagnosis of Alzheimer's disease (AD) is not available in China. The international criteria is not a proper choice due to issues such as translation and lead to low diagnostic rate and high rate of missed diagnosis. The research group of Alzheimer's Disease Chinese (ADC) reviewed knowledge and techniques in neuropsychology, neuroimaging, molecular biology, and clinical neurology, and systematically studied the detection techniques such as memory, language, visuospatial, executive function, and medial temporal lobe visual scores on MRI, and their optimal threshold and diagnostic value for the diagnosis of AD. Through a systematic review and consensus meeting, a diagnostic framework for screening AD in the Chinese population was established. Among these methods, an operational standard for clinical pathology models increased the diagnostic sensitivity by 15%. The sensitivity and specificity of screening memory impairment increased by 18.1% and 11.6%, respectively. The sensitivity of screening medial temporal lobe atrophy increased by 24.5% and missed diagnosis was decreased by 34.5%. An operational standard for clinical biology models, incorporating the latest molecular imaging and molecular biology techniques, has enabled the early diagnosis of AD in China. The framework combines a principled diagnostic guideline with an operational screening protocol, which is applicable to all clinical settings and of great significance for the early detection, early diagnosis and early treatment of AD.

Pulmonary PET imaging confirms preferential lung target occupancy of an inhaled bronchodilator

BackgroundPositron emission tomography (PET) is a non-invasive molecular imaging technique that traces the distribution of radiolabeled molecules in experimental animals and human subjects. We hypothesized that PET could be used to visualize the binding of the bronchodilator drug ipratropium to muscarinic receptors (MR) in the lungs of living non-human primates (NHP). The objectives of this study were two-fold: (i) to develop a methodology for quantitative imaging of muscarinic receptors in NHP lung and (ii) to estimate and compare ipratropium-induced MR occupancy following drug administration via intravenous injection and inhalation, respectively.MethodsA series of PET measurements (n = 18) was performed after intravenous injection of the selective muscarinic radioligand 11C-VC-002 in NHP (n = 5). The lungs and pituitary gland (both rich in MR) were kept in the field of view. Each PET measurement was followed by a PET measurement preceded by treatment with ipratropium (intravenous or inhaled).ResultsRadioligand binding was quantified using the Logan graphical analysis method providing the total volume of distribution (VT). Ipratropium reduced the VT in the lung and pituitary in a dose-dependent fashion. At similar plasma ipratropium concentrations, administration by inhalation produced larger reductions in VT for the lungs. The plasma-derived apparent affinity for ipratropium binding in the lung was one order of magnitude higher after inhalation (Kiih = 1.01 nM) than after intravenous infusion (Kiiv = 10.84 nM).ConclusionQuantitative muscarinic receptor occupancy imaging by PET articulates and quantifies the therapeutic advantage of the inhaled route of delivery and provides a tool for future developments of improved inhaled drugs.

Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair.

Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles (AuNP) to selectively and stably deliver the molecular probe intravenously to tumors. We optimized the properties of Cy7MX-loaded AuNPs using optical spectroscopy and tested the delivery mechanism and binding affinity using the DLD1 colon cancer cell line in vitro. A 10:1 ratio of Cy7MX-AuNPs demonstrated a strong AP site-specific binding and the cumulative release profile demonstrated 97% release within 12 min from a polar to a nonpolar environment. We further demonstrated targeted delivery using imaging and biodistribution studies in vivo in an xenografted mouse model. This work lays a foundation for the development of real-time molecular imaging techniques that are poised to yield quantitative measures of the efficacy and temporal profile of cytotoxic chemotherapies.

Relationship between the expression of PD-1/PD-L1 and 18F-FDG uptake in bladder cancer.

Immunotherapy aimed at inhibiting the PD-1/PD-L1 immune checkpoint has been approved and used successfully for the treatment of bladder cancer. The identification of markers predictive of response to immune checkpoint inhibitors is critical to advancing the success of this therapy. 18F-FDG PET/CT is a molecular imaging technique that can provide phenotypic information on malignant tumours. It is currently unknown whether there is a relationship between 18F-FDG uptake and expression of PD-1/PD-L1 in bladder cancer. In this study, we investigated whether PD-1/PD-L1 expression is associated with 18F-FDG uptake in bladder cancer, and whether 18F-FDG PET/CT imaging can be used to predict the PD-1/PD-L1 status of bladder cancer. A retrospective analysis was performed in 63 patients with bladder cancer who had undergone 18F-FDG PET/CT before surgical resection. Maximum standardized uptake values (SUVmax) were determined. SUVmax was significantly higher in PD-1-positive patients than in PD-1-negative patients (33.0 ± 13.9 and 19.6 ± 14.2, respectively; P = 0.032), and in PD-L1-positive patients than in PD-L1-negative patients (29.1 ± 15.6 and 15.8 ± 11.4, respectively; P < 0.0001). In a multivariate analysis SUVmax was significantly associated with both PD-1 expression and PD-L1 expression (P = 0.021 and P = 0.003, respectively). Using a SUVmax cut-off value of 22.7, PD-1 status and PD-L1 status could be predicted with accuracies of 71.4% and 77.8%, respectively. Higher 18F-FDG uptake by bladder cancer is associated with elevated PD-1/PD-L1 expression. 18F-FDG PET/CT may be useful for predicting the PD-1/PD-L1 status of bladder cancer and for determining the optimal therapeutic strategy.

PET imaging in patients with brain metastasis-report of the RANO/PET group.

Brain metastases (BM) from extracranial cancer are associated with significant morbidity and mortality. Effective local treatment options are stereotactic radiotherapy, including radiosurgery or fractionated external beam radiotherapy, and surgical resection. The use of systemic treatment for intracranial disease control also is improving. BM diagnosis, treatment planning, and follow-up is most often based on contrast-enhanced magnetic resonance imaging (MRI). However, anatomic imaging modalities including standard MRI have limitations in accurately characterizing posttherapeutic reactive changes and treatment response. Molecular imaging techniques such as positron emission tomography (PET) characterize specific metabolic and cellular features of metastases, potentially providing clinically relevant information supplementing anatomic MRI. Here, the Response Assessment in Neuro-Oncology working group provides recommendations for the use of PET imaging in the clinical management of patients with BM based on evidence from studies validated by histology and/or clinical outcome.

Samidorphan attenuates the effects of buprenorphine in rat models evaluating abuse potential

Over the past decade rapid advancements in molecular imaging (MI) and artificial intelligence (AI) have revolutionized traditional musculoskeletal radiology. Molecular imaging refers to the ability of various methods to in vivo characterize and quantify biological processes, at a molecular level. The extracted information provides the tools to understand the pathophysiology of diseases and thus to early detect, to accurately evaluate the extend and to apply and evaluate targeted treatments. At present, molecular imaging mainly involves CT, MRI, radionuclide, US, and optical imaging and has been reported in many clinical and preclinical studies. Although originally MI techniques targeted at central nervous system disorders, later on their value on musculoskeletal disorders was also studied in depth. Meaningful exploitation of the large volume of imaging data generated by molecular and conventional imaging techniques, requires state-of-the-art computational methods that enable rapid handling of large volumes of information. AI allows end-to-end training of computer algorithms to perform tasks encountered in everyday clinical practice including diagnosis, disease severity classification and image optimization. Notably, the development of deep learning algorithms has offered novel methods that enable intelligent processing of large imaging datasets in an attempt to automate decision-making in a wide variety of settings related to musculoskeletal trauma. Current applications of AI include the diagnosis of bone and soft tissue injuries, monitoring of the healing process and prediction of injuries in the professional sports setting. This review presents the current applications of novel MI techniques and methods and the emerging role of AI regarding the diagnosis and evaluation of musculoskeletal trauma.

Neuropsychiatric factor and polymorphism gene in internet addiction

Internet addiction (IA) has been described as ‘excessive or poorly controlled preoccupation, urges, or behaviors regarding computer use and internet access that lead to impairment or distress. Excessive internet user has emerged as a leading cause of behavioral and developmental problems in adolescents. There are several factors that influence the occurrence of internet addiction. The risk factors can be categorized by a social factor, psychiatric factor and biological factor. Some studies have found varied results. Molecular and functional imaging techniques have been increasingly used for the analysis of neurobiological changes and neurochemical correlates of IA. MRI (Magnetic Resonance Imaging) studies demonstrate that structural changes in the frontal cortex are associated with functional abnormalities in Internet-addicted subjects. Recent research has implicated the role of the striatal dopaminergic system in the behavioral maladaptation associated with IA. It provided evidence for a molecular genetic link between serotonergic and dopaminergic neurotransmission and Internet addiction like dopamine polymorphism the DRD2/ANKKI Taq Ia and COMT Val158metpolymorphism and the gene coding for the nicotinic acetylcholine receptor subunit alpha 4 (CHRNA4). As both the genetic and personality traits are known to play a role in other addiction it is likely that same mechanism (biopsychosocial) underlie Internet addiction.

PH-weighted molecular MRI in human traumatic brain injury (TBI) using amine proton chemical exchange saturation transfer echoplanar imaging (CEST EPI).

Cerebral acidosis is a consequence of secondary injury mechanisms following traumatic brain injury (TBI), including excitotoxicity and ischemia, with potentially significant clinical implications. However, there remains an unmet clinical need for technology for non-invasive, high resolution pH imaging of human TBI for studying metabolic changes following injury. The current study examined 17 patients with TBI and 20 healthy controls using amine chemical exchange saturation transfer echoplanar imaging (CEST EPI), a novel pH-weighted molecular MR imaging technique, on a clinical 3T MR scanner. Results showed significantly elevated pH-weighted image contrast (MTRasym at 3 ppm) in areas of T2 hyperintensity or edema (P < 0.0001), and a strong negative correlation with Glasgow Coma Scale (GCS) at the time of the MRI exam (R2 = 0.4777, P = 0.0021), Glasgow Outcome Scale - Extended (GOSE) at 6 months from injury (R2 = 0.5334, P = 0.0107), and a non-linear correlation with the time from injury to MRI exam (R2 = 0.6317, P = 0.0004). This evidence suggests clinical feasibility and potential value of pH-weighted amine CEST EPI as a high-resolution imaging tool for identifying tissue most at risk for long-term damage due to cerebral acidosis.