Podcasts about positron emission tomography pet

Prof. Mark Solms, a neuroscientist and psychoanalyst, discusses his groundbreaking work on consciousness, challenging conventional cortex-centric views and emphasizing the role of brainstem structures in generating consciousness and affect. MLST is sponsored by Brave: The Brave Search API covers over 20 billion webpages, built from scratch without Big Tech biases or the recent extortionate price hikes on search API access. Perfect for AI model training and retrieval augmentated generation. Try it now - get 2,000 free queries monthly at http://brave.com/api. Key points discussed: The limitations of vision-centric approaches to consciousness studies. Evidence from decorticated animals and hydranencephalic children supporting the brainstem's role in consciousness. The relationship between homeostasis, the free energy principle, and consciousness. Critiques of behaviorism and modern theories of consciousness. The importance of subjective experience in understanding brain function. The discussion also explored broader topics: The potential impact of affect-based theories on AI development. The role of the SEEKING system in exploration and learning. Connections between neuroscience, psychoanalysis, and philosophy of mind. Challenges in studying consciousness and the limitations of current theories. Mark Solms: https://neuroscience.uct.ac.za/contacts/mark-solms Show notes and transcript: https://www.dropbox.com/scl/fo/roipwmnlfmwk2e7kivzms/ACjZF-VIGC2-Suo30KcwVV0?rlkey=53y8v2cajfcgrf17p1h7v3suz&st=z8vu81hn&dl=0 TOC (*) are best bits 00:00:00 1. Intro: Challenging vision-centric approaches to consciousness * 00:02:20 2. Evidence from decorticated animals and hydranencephalic children * 00:07:40 3. Emotional responses in hydranencephalic children 00:10:40 4. Brainstem stimulation and affective states 00:15:00 5. Brainstem's role in generating affective consciousness * 00:21:50 6. Dual-aspect monism and the mind-brain relationship 00:29:37 7. Information, affect, and the hard problem of consciousness * 00:37:25 8. Wheeler's participatory universe and Chalmers' theories 00:48:51 9. Homeostasis, free energy principle, and consciousness * 00:59:25 10. Affect, voluntary behavior, and decision-making 01:05:45 11. Psychoactive substances, REM sleep, and consciousness research 01:12:14 12. Critiquing behaviorism and modern consciousness theories * 01:24:25 13. The SEEKING system and exploration in neuroscience Refs: 1. Mark Solms' book "The Hidden Spring" [00:20:34] (MUST READ!) https://amzn.to/3XyETb3 2. Karl Friston's free energy principle [00:03:50] https://www.nature.com/articles/nrn2787 3. Hydranencephaly condition [00:07:10] https://en.wikipedia.org/wiki/Hydranencephaly 4. Periaqueductal gray (PAG) [00:08:57] https://en.wikipedia.org/wiki/Periaqueductal_gray 5. Positron Emission Tomography (PET) [00:13:52] https://en.wikipedia.org/wiki/Positron_emission_tomography 6. Paul MacLean's triune brain theory [00:03:30] https://en.wikipedia.org/wiki/Triune_brain 7. Baruch Spinoza's philosophy of mind [00:23:48] https://plato.stanford.edu/entries/spinoza-epistemology-mind 8. Claude Shannon's "A Mathematical Theory of Communication" [00:32:15] https://people.math.harvard.edu/~ctm/home/text/others/shannon/entropy/entropy.pdf 9. Francis Crick's "The Astonishing Hypothesis" [00:39:57] https://en.wikipedia.org/wiki/The_Astonishing_Hypothesis 10. Frank Jackson's Knowledge Argument [00:40:54] https://plato.stanford.edu/entries/qualia-knowledge/ 11. Mesolimbic dopamine system [01:11:51] https://en.wikipedia.org/wiki/Mesolimbic_pathway 12. Jaak Panksepp's SEEKING system [01:25:23] https://en.wikipedia.org/wiki/Jaak_Panksepp#Affective_neuroscience

Positron Emission Tomography (PET) combined with Computed Tomography (CT) is a powerful imaging modality used in oncology for diagnosis, staging, and treatment monitoring. However, one limitation of PET/CT is the need for accurate attenuation correction (AC) to account for tissue density variations. Traditionally, low-dose CT scans are used for AC, but these contribute to patient radiation exposure. In a new study, researchers Kevin C. Ma, Esther Mena, Liza Lindenberg, Nathan S. Lay, Phillip Eclarinal, Deborah E. Citrin, Peter A. Pinto, Bradford J. Wood, William L. Dahut, James L. Gulley, Ravi A. Madan, Peter L. Choyke, Ismail Baris Turkbey, and Stephanie A. Harmon from the National Cancer Institute proposed an artificial intelligence (AI) tool to generate attenuation-corrected PET (AC-PET) images directly from non-attenuation-corrected PET (NAC-PET) images, reducing the reliance on CT scans. Their research paper was published in Oncotarget's Volume 15 on May 7, 2024, entitled, “Deep learning-based whole-body PSMA PET/CT attenuation correction utilizing Pix-2-Pix GAN.” Full blog - https://www.oncotarget.org/2024/07/11/ai-for-improved-pet-ct-attenuation-correction-in-prostate-cancer-imaging/ Paper DOI - https://doi.org/10.18632/oncotarget.28583 Correspondence to - Stephanie A. Harmon - stephanie.harmon@nih.gov Video short - https://www.youtube.com/watch?v=0mZItCB8AtI Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28583 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, deep learning, PSMA PET, attenuation correction About Oncotarget Oncotarget is an open-access, peer-reviewed journal that has published primarily oncology-focused research papers since 2010. These papers are available to readers (at no cost and free of subscription barriers) in a continuous publishing format at Oncotarget.com. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Cerianna is an FDA approved molecular imaging agent that has the ability to tell the doctor the receptor status of all the tumors—essentially creating a “whole-body" picture of estrogen receptor (ER) positive lesions in recurrent or metastatic breast cancer (MBC). The ability of physicians to more precisely “visualize” the disease may be instructive in determining the most appropriate course of treatment. Cerianna is administered as a single intravenous injection, and then imaged using a Positron Emission Tomography (PET) scan. Cerianna is used as an adjunct to biopsy.An expert panel of leading healthcare oncology providers and researchers have recently identified a number of potential clinical use cases for Cerianna including: detecting ER+ lesions when considering endocrine therapy for patients at initial diagnosis with MBC or after progression of metastatic disease; and assessing ER status of lesions that are difficult or dangerous to biopsy, when other imaging tests are uncertain or suspicious. or biopsy is non-diagnostic.Breast Cancer is Personal. Shouldn't your Diagnostic Imaging Test Be as Well? Listen to the episode for all the most latest clinical updates on Cerianna and check out our episode notes on our website for more information. Our thanks to GE Healthcare for their support of this podcast.

Microglial cells are responsible for sensing and driving the immune response in the central nervous system. Their activity, be it supportive or destructive, can be at the root of many different neuroinflammatory conditions including diseases like MS, ALS, Alzheimer's, Parkinson's, and TBI (Traumatic Brain Injury), but may also play a large role in the vague hallmark symptoms of complex and chronic disease like brain fog, fatigue, pain, alertness and mood changes including OCD, ADD, and depression. Dr Singhal systematically walks us through an easily understood description of the types of cells in the brain (neurons, macroglia (astrocytes & oligodendrocytes), microglia) and their functions. The microglia are a fascinating type of neuroimmune cell that sense and act protectively in good times and then can change shape and release various cytokines, chemokine and neurotransmitters in response to the development of disease, which then impacts microglia function further. We used to only be able to see this on autopsy- there are no blood tests available to measure microglial activation (although neurofilament light chains (NfL) from neurons and glial fibrillary acid protein (GFAP) from astrocytes can reflect central nervous system cellular injury). But PET imaging can visualize microglial activation! Dr Singhal explains in elucidating detail the nature, function, and power of Positron Emission Tomography (PET) imaging, like starting with the Big Bang, anti-matter particles, medical cyclotrons and gamma rays. “PET brings physics, chemistry and biology together in real time to provide novel insights at a cellular and molecular level”, including microglial activation. “If you know yourself and know your enemy, you'll win 1000 battles” is the way he describes what PET can do for neuroinflammatory conditions. We end the show with a discussion of treatment theories and options targeting microglial activation. It's a combination of re-evaluating known therapies (even the old antibiotic minocycline!) for their impact on microglia as well as mention of some novel therapies, including a nasal spray ‘vaccine' for MS. Of course, we bring up non-pharmacologic therapy potentials including exercise, the Ayurvedic perspective including panchakarma detoxification, the power of breathing to impact cerebrospinal fluid flow, ketogenic diet, and consideration of various adaptogenic herbs with the goal of supporting the immune system's intelligence.

Maurizio Corbetta is Full Professor and Chair of Neurology in the Department of Neuroscience at the University of Padua, Italy. He is also the founding director of the new Padua Neuroscience Center, a highly interdisciplinary research programme centered on the idea of brain networks in health and society. After receiving is M.D. from the University of Pavia in Italy, he carried out a residency in Neurology at the University of Verona. In 1990 he moved to US, carting out a fellowship in NeuroImaging at Barnes Hospital at Wash U in St. Louis. While in St. Louis, he worked his way up to being the Norman J. Strupp Professor of Neurology, and Professor of Radiology, Anatomy, Neurobiology Bioengineering and Neuroscience at Wash University, as well as Director of Stroke and Brain Injury Rehabilitation at the Rehabilitation Institute of St. Louis. He moved back to Italy, to teh University of Padua, in 2016. Prof. Corbetta has pioneered experiments on the neural mechanisms of human attention using Positron Emission Tomography (PET). He has discovered two brain networks dedicated to attention control, the dorsal and ventral attention networks, and developed a brain model of attention. His clinical work has focused on the physiological correlates of focal injury. He has developed a pathogenetic model of the syndrome of hemispatial neglect. He is currently developing novel methods for studying the functional organization of the brain using functional connectivity MRI, magneto-encephalography (MEG), and electro-corticography (EcoG). He is also working on the effects of focal injuries on the network organization of brain systems with an eye to neuromodulation. He is known for the high level of rigor and deep insight of his research, and has over 16 papers with over 1000 citations. Discussion In our conversation, we discuss some of the key people that influenced him, the incredible team of people at Washington University, as well as some of his early work. We also discuss his perspective on the utility and information in resting state fMRI. He's senior author of one of the most provocative and compelling explanations for resting state activity that I've seen: titled The secret life of predictive brains: what's spontaneous activity for? Pezzulo et al TICS 2021. We go on from there to discuss his perspective of the substantial importance and profound potential of systems level neuroimaging to not only basic neuroscience but also to clinical practice. Toward the end of our discussion, he highlights how diagnosis and treatment of stroke with neuromodulation can leverage current state of the art neuroimaging techniques.

Are you looking for an awesome cheatsheet that reviews the facts to know about diagnostic imaging for the NPTE? Look no further: www.kylericeprep.com/DI Aaralyn presents with a suspected Type 2 SLAP lesion and is undergoing diagnostic imaging using contrast to enhance visualization. Which of the following tests is the MOST likely to be performed? A. Computerized Tomography B. Bone Scintillography C. Magnetic Resonance Arthrogram (MRA) D. Positron Emission Tomography (PET-scan) Did you get this question wrong?! If you were stuck between two answers and selected the wrong one, then you need to visit www.NPTEPASS.com, to learn about the #1 solution to STOP getting stuck. --- Support this podcast: https://anchor.fm/thepthustle/support

Positron Emission Tomography (PET) has become the preferred test for diagnosing coronary artery disease. Although the clinical advantages are many, implementing a cardiac PET program requires planning, training, new technologies, and change management that can challenge CV leadership. In this episode we talk with two physicians who’ve led clinical and administrative leaders in the execution of cardiac PET programs, as well as myocardial blood flow (MBF). Cardiologist Gary Heller, MD, Medical Director of Molecular Imaging Services is the first physician to establish a PET program in Connecticut and has been involved in many other implementations since. And Richard Thompson, MD, cardiologist with Health First Medical Group, who championed the organization’s recent implementation of a cardiac PET program.MISmedical.commwilson@mismedical.com - Mark Wilson, EVP of Sales & Business Development

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.18.302943v1?rss=1 Authors: Garcia Guerra, S., Spadoni, A., Mitchell, J., Strigo, I. A. Abstract: Molecular mechanisms of the interaction between pain and reward associated with pain relief processes in the human brain are still incompletely understood. This is partially due to the invasive nature of the available techniques to visualize and measure metabolic activity. Positron Emission Tomography (PET) radioligand studies using radioactive substances are still the only available modality to date that allows for the investigation of the molecular mechanisms in the human brain. For pain and reward studies, the most commonly studied PET radiotracers are [11C]-carfentanil (CFN) and [11C]- or [18F]-diprenorphine (DPN), which bind to opioid receptors, and [11C]-raclopride (RAC) and [18F]-fallypride (FAL) tracers, which bind to dopamine receptors. The current meta-analysis looks at 15 pain-related studies using opioid radioligands and 8 studies using dopamine radioligands in an effort to consolidate the available data into the most likely activated regions. Our primary goal was to identify regions of shared opioid/dopamine neurotransmission during pain-related experiences. SDM analysis of previously published voxel coordinate data showed that opioidergic activations were strongest in the bilateral caudate, thalamus, right putamen, cingulate gyrus, midbrain, inferior frontal gyrus, and left superior temporal gyrus. The dopaminergic studies showed that the bilateral caudate, thalamus, right putamen, cingulate gyrus, and left putamen had the highest activations. We were able to see a clear overlap between opioid and dopamine activations in a majority of the regions during pain-related processing, though there were some unique areas of dopaminergic activation such as the left putamen. Regions unique to opioidergic activation include the midbrain, inferior frontal gyrus, and left superior temporal gyrus. By investigating the regions of dopaminergic and opioidergic activation, we can potentially provide more targeted treatment to these sets of receptors in patients with pain conditions. These findings could eventually assist in the development of more targeted medication in order to help treat pain conditions and simultaneously prevent physical dependency. Copy rights belong to original authors. Visit the link for more info

Coming up on Biotechnology Focus Radio :  Toronto’s Fusion Pharmaceuticals closes a US$25M Series A financing round led by Johnson & Johnson Innovation and BioTalent Canada releases Paving the Way, its latest labour market report. We have this and much more for you on this week’s show. Welcome to another episode of Biotechnology Focus Radio. I’m your host Shawn Lawrence, here to give you a rundown of this week’s top stories on the Canadian biotech scene. Story 1 Our first story this week has roots in Canada’s two biggest cities, with Enigma Biomedical Group, a Toronto based company focusing enhancing access to key technologies particularily those dealing with molecular imaging and medicine, reaching a clinical research agreement with the McGill University Research Centre for Studies in Aging in Montreal, in support of multiple projects to take place over the next several years. As part of the agreement, Enigma will provide funding for various research projects, and through its US entity Cerveau Technologies, Inc. The research projects are for studies of an early stage imaging agent (MK-6240) to be used in Positron Emission Tomography (PET) scans for assessing the status and progression of neurofibrillary tangles (NFTs) in the brain. What are NFTs exactly, well they are made up of aggregated tau protein and are a hallmark of several neurodegenerative diseases, including Alzheimer’s disease. According to Dr. Serge Gauthier, Director of the AD & Related Disorders Research Unit of the McGill University Research Center for Studies in Aging, the ability to visualize and quantify tau in the brain will further facilitate therapeutic research in the field of Alzheimer's disease. Cerveau Technologies  will supply the MK-6240 precursor needed for the initiatives.   Story Our next story takes us to HALIFAX, Nova Scotia, where Appili Therapeutics has announced it is receiving $2,803,148 from the Atlantic Canada Opportunities Agency (ACOA), under the Atlantic Innovation Fund (AIF). This funding will enable Appili to take its first drug, ATI-1501 – a taste-masked, oral antibiotic that treats anaerobic infections like Clostridium difficile – through clinical trials, including human clinical trial, and to be ready for market approval.  Of note, the drug is a reformulation of metronidazole, a front-line treatment for anaerobic bacterial infections. Over 10 million metronidazole prescriptions are issued in the U.S. annually. The company hopes to begin these clinical trials this year and is presently manufacturing the clinical batch of ATI-1501 to good manufacturing practices (GMP), the standard required by the Health Canada and the U.S. Food and Drug Administration (FDA). As for why the company is focused on reformulating metronidazole, well, the bitter taste of these tablets often results in poor patient compliance, which leads to the spread of infections and recurrent infections within the patients. In particular, reluctance to complete the prescribed course of antibiotics is highly problematic among children and the elderly with swallowing issues, who must crush and re-suspend tablets to ingest the metronidazole. The company says that ATI-1501 has been optimized to improve palatability, which should significantly reduce the instances of patient reluctance to take the drug.  How it works is once it is ingested, it kills anaerobic bacteria by interfering with their DNA, leading to bacterial cell death thus clearing up the infection. Story Across the country, in Vancouver BC, Zymeworks Inc. reports that the U.S. Food and Drug Administration has granted an orphan drug designation to its lead product candidate, ZW25, as a treatment for gastric cancer, including cancer of the gastroesophageal junction. The FDA grants orphan drug designation to biological products that are intended to treat a rare disease or condition, which is generally defined as affecting a patient population of fewer than 200,000 people in the United States. Orphan drug designation provides the sponsor certain financial incentives, including tax credits, the waiver of associated application fees, and a period of marketing exclusivity if the product candidate receives the first marketing approval for the indication for which it has such designation. The drug is currently being evaluated in an adaptive Phase 1 clinical trial in the U.S., based on the company’s Azymetric platform. It is a bispecific antibody that can simultaneously bind two non-overlapping epitopes, known as biparatopic binding, of HER2 resulting in dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and enhanced effector function. These combined mechanisms of action have led to significant anti-tumor activity in preclinical models. This marks the drugs second orphan drug designation, in addition to ovarian cancer, which was granted last year. Story Last week, BioTalent Canada released its latest labour market report, title Paving the Way. Funded in part by the Government of Canada's Labour Market Integration Program, the report surveyed skilled newcomers, immigrant serving agencies (ISAs) and employers, and made recommendations on how internationally educated professionals (IEPs) can better connect to jobs in Canada’s bio-economy. Key report findings included that internationally educated professionals arrive with the knowledge and skills needed by Canada’s bio-economy, with Two-thirds (67.6%) of those surveyed reporting having a minimum of a master’s degree and over half (56.8%) indicated that they have worked in biotech industry prior to immigrating to Canada. And yet the report also found that many talented newcomers continue to have their skills and experience overlooked by hiring managers. Rob Henderson, president and CEO of BioTalent Canada, says this is quite troubling as ours is a sector that struggles with access to talent, so it should be crucial for businesses to recognize newcomers as an important talent pool. The report highlights some of the obstacles hindering internationally educated professionals from entering into Canada’s biotechnology sector workforce, such as 51.9% saying they were finding it difficult to finding jobs in their own field, and 46.5% saying a lack of Canadian experience was an obstacle.  The report also suggests that Pre-screening for education experience validation may be a solution for skilled IEPs to connect to employers with Biotechnology employers that were surveyed supporting the concept of having access to pre-screened candidates. Moreover, a skills validation process would be an effective method of fast-tracking newcomers to biotech jobs in Canada. The full report is available online, to download a copy or view it, visit  biotalent.ca/PavingtheWay. Story Our final story takes us to Toronto, where Fusion Pharmaceuticals , a company first financially seeded by Fight Against Cancer Innovation Trust (FACIT) Inc., has closed a US$25M Series A financing, with Johnson & Johnson Innovation – JJDC, Inc. (JJDC) as the lead investor. Additional, new investors in the Series A round also included venture groups TPG Biotechnology Partners, HealthCap and Genesys Capital, as well as founding investor FACIT.  The financing is also strengthened by HealthCap’s specialized expertise having pioneered a new wave of successful radiotherapeutic companies. Fusion will use the financing proceeds to advance its lead program, FPX-01, into human clinical trials. FPX-01 is an antibody-targeted radiotherapy that seeks out a specific biomarker present on nearly all types of treatment-resistant cancers. Fusion’s technology, targeted alpha-particle emitting radiotherapeutics, combine the precision of molecular targeting agents such as antibodies with the potency of alpha-particle emitting radioisotopes to specifically attack and eradicate cancer cells. Alpha-particle emitting medical isotopes attack cancer cells using multiple mechanisms, including causing the type of DNA damage that the cancer cell cannot easily repair, reducing the likelihood of developing drug resistance. At the same time, alpha particle-emitting agents offer improved safe-handling features and can be administered in conventional cancer treatment facilities unlike previous generations of radiotherapeutics. In addition, Fusion is building its pipeline through access to a centyrin protein targeting platform in two licensing agreements with Janssen Biotech in transactions facilitated by J&J Innovation. The company itself is a spinout from the Centre for Probe Development and Commercialization (CPDC), which is a Centre of Excellence for Commercialization and Research Centre (CECR) located at McMaster University. The CPDC has facilities and major partnerships in Hamilton, Boston, Toronto and Ottawa. The company also received OICR funding support from its inception. As OICR's commercialization partner, FACIT provided corporate leadership (through its Executive-in-Residence program) as well as seed funding to launch Fusion and to attract the strategic partners, investors and the larger capital infusion necessary to grow the company, and continue its research around radiotherapeutics.   The company is led by Dr. John Valliant, who is the founder of both Fusion and CPDC. He was selected as one of the Canada’s top 40 under 40 in 2010 Well that wraps up another episode of the Biotechnology Focus Podcast. We hope you enjoyed it. Be sure to let us know what you think, and we’re also always looking for story ideas and suggestions for future shows, and of course we’d love to hear from you as well, simply reach out to us via twitter @biotechfocus, or by email at the following email address  press@promotivemedia.ca. And remember, you can also listen to past episodes online via our podcast portal at www.biotechnologyfocus.ca . For all of us here at Biotechnology Focus, thanks for listening.

This week the topic was Fourier analysis. We interviewed Heather Williams, who’s a medical physicist and works with Positron Emission Tomography (PET) scanners, as well as other medical scanning devices. We talked about her work and how maths is important in converting data from the scanner into images that can be used to diagnose patients. Show notes and more episodes via www.furthermaths.org.uk/podcasts

The application of microfluidics to the synthesis of Positron Emission Tomography (PET) tracers has been explored for more than a decade. Microfluidic benefits such as superior temperature control have been successfully applied to PET tracer synthesis. However, the design of a compact microfluidic platform capable of executing a complete PET tracer synthesis workflow while maintaining prospects for commercialization remains a significant challenge. This study uses an integral system design approach to tackle commercialization challenges such as the material to process compatibility with a path towards cost effective lab-on-chip mass manufacturing from the start. It integrates all functional elements required for a simple PET tracer synthesis into one compact radiochemistry platform. For the lab-on-chip this includes the integration of on-chip valves, on-chip solid phase extraction (SPE), on-chip reactors and a reversible fluid interface while maintaining compatibility with all process chemicals, temperatures and chip mass manufacturing techniques. For the radiochemistry device it includes an automated chip-machine interface enabling one-move connection of all valve actuators and fluid connectors. A vial-based reagent supply as well as methods to transfer reagents efficiently from the vials to the chip has been integrated. After validation of all those functional elements, the microfluidic platform was exemplarily employed for the automated synthesis of a Gastrin-releasing peptide receptor (GRP-R) binding the PEGylated Bombesin BN(7-14)-derivative (F-18]PESIN) based PET tracer.

Application of microfluidics to Positron Emission Tomography ( PET) tracer synthesis has attracted increasing interest within the last decade. The technical advantages of microfluidics, in particular the high surface to volume ratio and resulting fast thermal heating and cooling rates of reagents can lead to reduced reaction times, increased synthesis yields and reduced by-products. In addition automated reaction optimization, reduced consumption of expensive reagents and a path towards a reduced system footprint have been successfully demonstrated. The processing of radioactivity levels required for routine production, use of microfluidic-produced PET tracer doses in preclinical and clinical imaging as well as feasibility studies on autoradiolytic decomposition have all given promising results. However, the number of microfluidic synthesizers utilized for commercial routine production of PET tracers is very limited. This study reviews the state of the art in microfluidic PET tracer synthesis, highlighting critical design aspects, strengths, weaknesses and presenting several characteristics of the diverse PET market space which are thought to have a significant impact on research, development and engineering of microfluidic devices in this field. Furthermore, the topics of batch- and single-dose production, cyclotron to quality control integration as well as centralized versus de-centralized market distribution models are addressed.

Molecular imaging-and especially Positron Emission Tomography (PET)-is of increasing importance for the diagnosis of various diseases and thus is experiencing increasing dissemination. Consequently, there is a growing demand for appropriate PET tracers which allow for a specific accumulation in the target structure as well as its visualization and exhibit decay characteristics matching their in vivo pharmacokinetics. To meet this demand, the development of new targeting vectors as well as the use of uncommon radionuclides becomes increasingly important. Uncommon nuclides in this regard enable the utilization of various selectively accumulating bioactive molecules such as peptides, antibodies, their fragments, other proteins and artificial structures for PET imaging in personalized medicine. Among these radionuclides, 89Zr (t1/2 = 3.27 days and mean Eβ+ = 0.389 MeV) has attracted increasing attention within the last years due to its favorably long half-life, which enables imaging at late time-points, being especially favorable in case of slowly-accumulating targeting vectors. This review outlines the recent developments in the field of 89Zr-labeled bioactive molecules, their potential and application in PET imaging and beyond, as well as remaining challenges.

Silicon-[18F]Fluorine (Si-18F) radiochemistry has recently emerged alongside other unconventional approaches such as aluminum-F-18 and boron-F-18 based labeling strategies, reshaping the landscape of modern F-18-radiochemistry. All these novel methodologies are driven by the demand for more convenient F-18-labeling procedures to further disseminate one of the most sophisticated imaging technologies, Positron Emission Tomography (PET). The PET methodology requires special radionuclides such as F-18 (one of the most prominent examples) to be introduced into bioactive molecules. Si-F-18 radiochemistry contributed greatly towards the development of new radiopharmaceuticals for PET imaging. Herein, we describe the radiochemical basics of Si-F-18 bond formation, the application of Si-F-18 tracers for PET imaging, and additionally, the inherent chemical intricacies of this methodology.

The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D-2-receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules such as receptor-ligands, is the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA-conjugates derivatized either directly at the benzoic acid ring system (SiFA-DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested their receptor affinities. We found D2-receptor affinities for all compounds in the nanomolar range (Ki(SiFA-DMFP) = 13.6 nM, Ki(SiFA-FP) = 33.0 nM, Ki(SiFA-DDMFP) = 62.7 nM and Ki(SiFA-M-FP) = 4.21 nM). The radiofluorination showed highest yields when 10 nmol of the precursors were reacted with F-18]fluoride/TBAHCO(3) in acetonitrile. After a reversed phased cartridge purification the desired products could be isolated as an injectable solution after only 10 min synthesis time with radiochemical yields (RCY) of more than 40% in the case of SiFA-DMFP resulting in specific activities >41 GBq/mu mol (>1,100 Ci/mmol). Furthermore, the radiolabeled products were shown to be stable in the injectable solutions, as well as in human plasma, for at least 90 min.

2 SUMMARY Pathologically-anatomical and immunhistochemistric investigation of ischemic myocardium in the pig Background: Different degrees of histological alteration have been seen in hibernating myocardium. Hibernation is associated with structural myocardial changes, which involve both the cardiomyocytes and the cardiac interstitium. The purpose of this study is to investigate the effects of chronic myocardial ischemia on histological patterns to understand the underlying mechanism of hibernation. Methods: A model of ischemic injury was produced in 16 pigs (German land breed) by placement of a modified stent graft in the left anterior descending artery (LAD), which initially produced 75% stenosis, followed by a slow complete occlusion. Wall motion abnormalities were investigated by Magnetic Resonance Imaging (MRI) and ultrasound images at day 7 after implantation. Metabolism and perfusion were imaged by Positron Emission Tomography (PET) at day 7 (group 1) and at day 28 (group 2). After PET images the animals were sacrificed and tissue samples were taken for histology. Results: Viability in PET is defined by a relative decrease in perfusion in an area where there is a relative increase in FDG (fluorodeoxyglucose) concentration. This is often referred to as a “mismatch” pattern. In the study nearly all pigs showed this “mismatch” in the LAD area. The following significant results could be found in the mismatched samples: the accumulation of collagen (0,12 ± 0,12 %, p < 0,05) in LAD samples compared to those taken from remote area (0,02 ± 0,02 %) and glycogen rich perinuclear zones in LAD samples (0,06 ± 0,03 %, p < 0,05). Despite the difficulties of reproducing a long-term hibernating myocardium in an animal model, one pig (No.8) demonstrated physiological alterations that can be compared to those of human beings with hibernating myocardium. After 28 days the artery of the pig was completely occluded. A mismatch was determined by PET, and wall motion abnormalities were present. Furthermore in cells which were exposed to a repetitive ischemia, a small degree of fibrosis and glycogen richness were shown. Conclusion: In contrast to various short-term hibernating myocardium models, no equivalent model exists for long-term hibernating myocardium over a time period of weeks or months yet. For this reason, the complete mechanism of chronic hibernating myocardium is still unclear. The fluent transition of the different heart failure up to the infarct as seen in the clinic reflect the dynamic process, the interindividuell differences and last but not least the reduced compensation abilities of the heart. Due to this it is difficult to find a matching in-vivo model that shows the same mechanism as humans. Therefore every small and large animal model is helpful for clarification.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.10.035352v1?rss=1 Authors: Norgaard, M., Beliveau, V., Ganz, M., Svarer, C., Pinborg, L. H., Keller, S. H., Jensen, P. S., Greve, D. N., Knudsen, G. M. Abstract: Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. The binding of benzodiazepines to the benzodiazepine receptor sites (BZR) located on GABAA receptors (GABAARs) potentiates the inhibitory effect of GABA leading to the anxiolytic, anticonvulsant and sedative effects used for treatment of those disorders. However, the function of GABAARs and the expression of BZR protein is determined by the GABAAR subunit stoichiometry (19 genes coding for individual subunits), and it remains to be established how the pentamer composition varies between brain regions and individuals. Here, we present a quantitative high-resolution in vivo atlas of the human brain BZRs, generated on the basis of [11C]flumazenil Positron Emission Tomography (PET) data. Next, based on autoradiography data, we transform the PET-generated atlas from binding values into BZR protein density. Finally, we examine the brain regional association with mRNA expression for the 19 subunits in the GABAAR, including an estimation of the minimally required expression of mRNA levels for each subunit to translate into BZR protein. This represents the first publicly available quantitative high-resolution in vivo atlas of the spatial distribution of BZR densities in the healthy human brain. The atlas provides a unique neuroscientific tool as well as novel insights into the association between mRNA expression for individual subunits in the GABAAR and the BZR density at each location in the brain. Copy rights belong to original authors. Visit the link for more info