Peter Scott

Peter Scott
University of Michigan | U-M · Department of Radiology

BSc, PhD

About

238
Publications
26,356
Reads
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4,144
Citations
Citations since 2017
130 Research Items
3173 Citations
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20172018201920202021202220230100200300400500600700
20172018201920202021202220230100200300400500600700
Introduction

Publications

Publications (238)
Article
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Gold nanoparticles (AuNPs) are cutting-edge platforms for combined diagnostic and therapeutic approaches due to their exquisite physicochemical and optical properties. Using the AuNPs physically produced by femtosecond pulsed laser ablation of bulk Au in deionized water, with a capping agent-free surface, the conjugation of functional ligands onto...
Article
The report describes an updated, fully automated method for the production of [11C]butyrate, validated for use in clinical studies. A commercially available GE Tracerlab FXM synthesis module was reconfigured to allow for air-free introduction of n-propyl magnesium chloride and to incorporate Sep-Pak cartridges to simplify and shorten the purificati...
Article
Cortical cholinergic deficits contribute to cognitive decline and other deficits in Parkinson's disease. Cross-sectional imaging studies suggest a stereotyped pattern of posterior-to-anterior cortical cholinergic denervation accompanying disease progression in Parkinson's disease. We used serial acetylcholinesterase PET ligand imaging to characteri...
Article
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Prior studies indicate more severe brainstem cholinergic deficits in Progressive Supranuclear Palsy (PSP) compared to Parkinson’s disease (PD), but the extent and topography of subcortical deficits remains poorly understood. The objective of this study is to investigate differential cholinergic systems changes in progressive supranuclear palsy (PSP...
Article
Imaging of misfolded proteins implicated in neurodegenerative disorders using positron emission tomography (PET) imaging has revolutionized dementia research. In this viewpoint, the development of radiotracers for tau PET is highlighted. We draw attention to key innovations that were essential to development of radiotracers for imaging tau, from ea...
Article
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To examine regional cerebral vesicular acetylcholine transporter (VAChT) ligand [¹⁸F]fluoroethoxybenzovesamicol ([¹⁸F]-FEOBV) PET binding in Parkinson’ disease (PD) patients with and without vestibular sensory conflict deficits (VSCD). To examine associations between VSCD-associated cholinergic brain deficits and postural instability and gait diffi...
Article
Positron emission tomography (PET) is a highly sensitive and versatile molecular imaging modality that leverages radiolabeled molecules, known as radiotracers, to interrogate biochemical processes such as metabolism, enzymatic activity, and receptor expression. The ability to probe specific molecular and cellular events longitudinally in a noninvas...
Article
Background: Imaging of cholesterol utilization is possible with the iodine-131 scintiscanning/SPECT agent, NP-59. This agent provided a non-invasive measure of adrenal function and steroid synthesis. However, iodine isotopes resulted in poor resolution, manufacturing challenges, and high radiation dosimetry to patients that have limited their use a...
Article
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Mitochondrial complex I (MC-I) is an essential component of brain bioenergetics and can be quantified and studied using positron emission tomography (PET). A specific high affinity 18 F radiotracer for MC-I enables monitoring of neurodegenerative disease progression and pathology via PET imaging. To facilitate clinical research studies tracking MC-...
Article
The [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) positron emission tomography (PET) ligand targets the vesicular acetylcholine transporter. Recent [18F]FEOBV PET rodent studies suggest that regional brain [18F]FEOBV binding may be modulated by dopamine D2-like receptor agents. We examined associations of regional brain [18F]FEOBV PET binding in Par...
Article
[68Ga]Ga-PSMA-11, a urea-based peptidomimetic, is a diagnostic radiopharmaceutical for positron emission tomography (PET) imaging that targets the prostate-specific membrane antigen (PSMA). The recent Food and Drug Administration approval of [68Ga]Ga-PSMA-11 for PET imaging of patients with prostate cancer, expected follow-up approval of companion...
Article
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Positron emission tomography (PET) is an important non-invasive tool to help guide the drug discovery and development process. Positron-emitting–radiolabeled drug candidates represent an important tool for drug hunters to gain insight into a drug's biodistribution and target engagement of exploratory biologic targets of interest. Recently, there ha...
Article
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Acetylcholine plays a major role in brain cognitive and motor functions with regional cholinergic terminal loss common in several neurodegenerative disorders. We describe age-related declines of regional cholinergic neuron terminal density in vivo using the positron emission tomography (PET) ligand [¹⁸F](–)5-Fluoroethoxybenzovesamicol ([¹⁸F]FEOBV),...
Article
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Mutations in the huntingtin gene (HTT) triggers aggregation of huntingtin protein ( m HTT), which is the hallmark pathology of neurodegenerative Huntington’s disease (HD). Development of a high affinity ¹⁸ F radiotracer would enable the study of Huntington’s disease pathology using a non-invasive imaging modality, positron emission tomography (PET)...
Article
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Purpose Positron emission tomography (PET) studies with radioligands for 18-kDa translocator protein (TSPO) have been instrumental in increasing our understanding of the complex role neuroinflammation plays in disorders affecting the brain. However, ( R )-[ ¹¹ C]PK11195, the first and most widely used TSPO radioligand has limitations, while the nex...
Article
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Background: The European Association of Urology (EAU) Prostate Cancer Guidelines Panel recommends risk groups for biochemically recurrent prostate cancer (BCR) to identify men at high risk of progression or metastatic disease. Recent United States Food and Drug Administration approval for 68Ga-PSMA-11 and growing availability of PSMA-directed PET i...
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[ ¹¹ C]Verubulin (a.k.a.[ ¹¹ C]MCP-6827), [ ¹¹ C]HD-800 and [ ¹¹ C]colchicine have been developed for imaging microtubules (MTs) with positron emission tomography (PET). The objective of this work was to conduct an in vivo comparison of [ ¹¹ C]verubulin for MT imaging in mouse and rat brain, as well as an in vitro study with this radiotracer in rod...
Article
We prospectively investigated the performance of the prostate-specific membrane antigen (PSMA) ligand 68Ga-PSMA-11 for detecting prostate adenocarcinoma in patients with elevated prostate-specific-antigen (PSA) after initial therapy. Methods: 68Ga-PSMA-11 hybrid positron emission tomography (PET) was performed in 2005 patients at the time of bioche...
Article
This article describes a sequential Ir/Cu-mediated process for the meta-selective C-H radiofluorination of (hetero)arene substrates. In the first step, Ir-catalyzed C(sp2)-H borylation affords (hetero)aryl pinacolboronate (BPin) esters. The intermediate organoboronates are then directly subjected to copper-mediated radiofluorination with [18F]tetra...
Article
Since the earliest days of nuclear medicine, there has been interest in using PET and SPECT imaging to interrogate and quantify the cholinergic system. In this Viewpoint we highlight key milestones in the development of cholinergic imaging agents, including identification of radiopharmaceuticals targeting the receptors, transporters, and enzymes of...
Article
Full-text available
Clinical effects of anti-cholinergic drugs implicate cholinergic systems alterations in the pathophysiology of some cardinal motor impairments in Parkinson’s disease. The topography of affected cholinergic systems deficits and motor domain specificity are poorly understood. Parkinson's disease patients (n = 108) underwent clinical and motor assessm...
Article
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Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Results This commentary of highlights has resulted in 23 different topics selected by each member of the Editorial Board addressing a variety of aspects ra...
Article
Radiochemical conversion is an important term to be included in the “Consensus nomenclature rules for radiopharmaceutical chemistry”. Radiochemical conversion should be used to define reaction efficiency by measuring the transformation of components in a crude reaction mixture at a given time, whereas radiochemical yield is better suited to define...
Article
Glycogen synthase kinase 3 (GSK-3) is an enzyme that is dysregulated in oncology neurodegeneration, neuroinflammation and several mental health illnesses. As such, GSK-3 is a long-sought after target for positron emission tomography (PET) imaging and therapeutic intervention. Herein, we report on the development and radiofluorination of two oxazole...
Article
Full-text available
Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field. Results This commentary of highlights has resulted in 19 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man app...
Article
Gallium‐68 has seen the largest growth in nuclear medicine usage of any isotope over the past 10 years. To design an ideal chelator for ⁶⁸Ga, a range of criteria need to be met: fast radiolabeling, quantitative incorporation, mild radiolabeling conditions, low precursor concentration (high molar activity), metal ion selectivity, versatile and robus...
Article
This chapter discusses recent trends in the use of radiopharmaceuticals in oncology. The first report of the internal use of radionuclides for cancer therapy emerged in 1913, when Frederick Proescher used intravenous injections of soluble radium‐223 salts for the treatment of patients with a variety of diseases, including uterine cancer and leukemi...
Article
Clinical applications of radiopharmaceuticals in the practice of neuro‐nuclear medicine are shifting from traditional planar studies of cerebrospinal fluid (CSF) and cerebral blood flow (CBF) to tomographic single‐photon emission computed tomography (SPECT) and positron emission tomography (PET) studies of brain molecular targets, such as dopamine...
Article
New fluorine‐18 radiochemistry has been extensively reviewed in recent years, and this chapter focuses on highlighting key new methods utilizing [¹⁸F]F‐ as a reagent for the production of fluorine‐18 positron emission tomography imaging agents. The two main approaches to radiolabeling with [¹⁸F]fluoride were nucleophilic substitution reactions (SN2...
Chapter
Interest in ⁸⁹Zr stems from the excellent image quality reported in both preclinical and clinical studies, but also from the ease, efficiency, and reproducibility of the bioconjugation chemistry and radio chemistry required to make ⁸⁹Zr‐labelled radiotracers. Other advantages include the low cost of production, automated isolation from the cyclotro...
Article
This chapter describes the tremendous challenges and costs of discovering and developing a new pharmaceutical and how we can de‐risk this process through translational and personal medicine approaches. It focuses on how positron emission tomography (PET) and novel PET radioligands are used to gain better understanding of a drug and its target, and...
Article
The clinical translation of a radiotracer will generally be faster compared to standard pharmaceuticals. This chapter provides an overview of the specific legal requirements that must be followed to move a radiopharmaceutical for positron emission tomography or single‐photon emission computed tomography imaging studies from bench to bedside in Euro...
Article
This chapter describes the production and isolation methods for obtaining the radionuclides used in single photon emission computed tomography (SPECT). It presents the radionuclide with a description of how it is produced along with typical separation/purification approaches presently used. SPECT imaging is dominated by technetium‐99m (99mTc), whic...
Article
The field of nuclear medicine has seen many important technical developments in the past seven decades, including improved radionuclide availability, new techniques for radiopharmaceutical synthesis, better imaging devices, and novel methods for image reconstruction and analysis. This chapter focuses on the early step of identifying appropriate che...
Article
This chapter identifies the most important milestones in the positron emission tomography (PET) industry that have led to quality control (QC) standardization and set the stage for automated solutions. It then introduces the progression of approaches to automation undertaken by different organizations. Discussion of these approaches, drivers, barri...
Article
In this chapter, the bibliography has been surveyed from 2000 to the present, and the 99mTc‐labelled imaging agents developed are summarized. In these years, new 99mTc‐labelling strategies have been developed, new 99mTc‐complexes have been proposed as probes with superior properties over older ones, and many research efforts have focused on the des...
Article
While neutron capture and charged‐particle reactions are used to produce the majority of therapeutic radionuclides, photonuclear reactions using electron linear accelerators are actively being investigated as a potential new route to produce and supply previously inaccessible or hard‐to‐obtain radionuclides. This chapter covers these different prod...
Article
Nitrogen‐13 has progressively been incorporated in the toolbox of positron emission tomography chemists, who have developed strategies for the in‐cyclotron production of different ¹³N‐labeled species, which have been used directly in different applications or further employed to prepare more complex labeled molecules. This chapter covers the main a...
Article
This chapter highlights the recent advances in Cu‐mediated radiohalogenation of organoboranes and discusses how this method has enabled the development of highly efficient radiolabeling strategies for the less studied Br and At heavy halides. Cu complexes have been among the most reported additives in organoborane radiohalogenation, as these system...
Article
Carbon‐11 decays into stable boron‐11 and has a physical half‐life of 20.4 minutes. The emergence of medical cyclotrons in the 1960s and positron emission tomography in the late 1970s has driven ¹¹C radiochemistry research to meet the demands for new or improved tracers at an expanding array of biological targets. This review chapter highlights cor...
Article
Positron emission tomography (PET) drugs are unique in that they are produced in small batches by decentralized manufacturers/pharmacies due to their physical characteristics, which do not lend them to large‐scale production: namely, the shorter half‐lives of positron‐emitting radionuclides. Through congressional action, specific legislative langua...
Article
This chapter discusses the production methods for the most commonly used short‐lived positron emission tomography (PET) radionuclides, with an emphasis on the methods used with the typical low‐ to medium‐energy (15–30MeV) cyclotrons used for the production of radiopharmaceuticals for PET imaging studies. The characteristics of the group of most‐use...
Article
Research into diagnosis through positron emission tomography (PET) and the treatment of radionuclide therapy have entered the spotlight with the emergence of molecular imaging and targeted therapies. It is well known that PET images are much superior to and more accurate than single photon emission computed tomography, and hence there is an absolut...
Article
As with most pharmaceutical developments, the vast majority of nuclear medicine procedures that are applied to pediatric disorders and investigations utilize radiopharmaceuticals and imaging methods developed for adults. This chapter summarizes the well‐established or clinically approved nuclear medicine procedures but focuses on studies more commo...
Article
Clinically, the growth in radiotherapy has been in the use of targeted radiotherapeutics for the treatment of cancer, as shown in this chapter, but other emerging applications are also highlighted, including preclinical treatment of infections. There are two main ways that a radiopharmaceutical can be considered a theranostic. First, a radiopharmac...
Article
This chapter discusses the use of radiopharmaceuticals in the study of the heart for both the clinical care for the cardiovascular (CV) patient and advancing CV research. Cardiac morphology and performance are more commonly assessed based on electrocardiographical gating of an myocardial perfusion imaging (MPI) study. A variety of PET radiopharmace...
Article
The field of radiochemistry is constantly evolving to meet the needs for increased starting amounts of radioactivity, and in the last couple of decades it has seen a move from manual radiochemistry to the use of automated synthesis modules supported by sophisticated software programs. This chapter provides an overview of radiopharmaceutical synthes...
Article
A new method for the synthesis of the highly selective delta opioid receptor (DOR) antagonist radiotracer N1′‐([¹¹C]methyl)naltrindole ([¹¹C]MeNTI) is described. The original synthesis required hydrogenation of a benzyl protecting group after ¹¹C‐labeling, which is challenging in modern radiochemistry laboratories that tend to be heavily automated...
Article
Full-text available
Purpose To optimize the direct production of ⁶⁸Ga on a cyclotron, via the ⁶⁸Zn(p,n)⁶⁸Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced ⁶⁸Ga, extraction of [⁶⁸Ga]GaCl3 and subsequent [⁶⁸Ga]Ga-PSMA-11 labeling using an automated synthesis module. Methods Irradiations of a 1.0 M solution of [⁶⁸Zn]Zn(NO3)2 in...
Article
Radiolabeled guanidines such as meta-iodobenzylguanidine (MIBG) find utility in nuclear medicine as both diagnostic imaging agents and radiotherapeutics and, over the years, numerous methods for incorporating radionuclides into guanidines have been developed. In connection with a project developing new positron emission tomography (PET) radiotracer...
Article
Full-text available
Background In the US, EU and elsewhere, basic clinical research studies with positron emission tomography (PET) radiotracers that are generally recognized as safe and effective (GRASE) can often be conducted under institutional approval. For example, in the United States, such research is conducted under the oversight of a Radioactive Drug Research...
Article
When utilizing [¹⁸F]tetrabutylammonium fluoride ([¹⁸F]TBAF) in the synthesis of ¹⁸F-labeled radiotracers for clinical positron emission tomography (PET) imaging, it is necessary to confirm that residual TBA levels in formulated doses do not exceed established specifications (≤2.6 mg per patient dose). Historically this has been accomplished using H...
Article
Imaging of the opioid system was one of the earliest applications of Positron Emission Tomography (PET) imaging in neuroscience that remains in widespread use today and in the age of the opioid crisis the technique is as important as ever. In this viewpoint the rich history of opioid imaging using PET is highlighted, including discussion of the pre...
Article
The radiotracers [¹¹C]COU and [¹¹C]PHXY are potential PET imaging agents for in vivo studies of monoamine oxidases (MAO), as previously shown in rodent and primate brain. One-pot, automated methods for the radiosynthesis of [¹¹C]PHXY and [¹¹C]COU were developed to provide reliable and improved radiochemical yields. Although derived from the structu...
Article
Full-text available
The implication of the receptor for advanced glycation end-products (RAGE) in numerous diseases and neurodegenerative disorders makes it interesting both as a therapeutic target and as an inflammatory biomarker. In the context of investigating RAGE as a biomarker, there is interest in developing radiotracers that will enable quantification of RAGE...
Preprint
Full-text available
Purpose: To optimize the direct production of ⁶⁸Ga on a cyclotron, via the ⁶⁸Zn(p,n)⁶⁸Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced ⁶⁸Ga, extraction of [⁶⁸Ga]GaCl3 and subsequent [⁶⁸Ga]Ga-PSMA-11 labeling using an automated synthesis module. Methods: Irradiations of a 1.0 M solution of [⁶⁸Zn]Zn(NO3)2 i...
Preprint
Full-text available
Purpose: To optimize the direct production of ⁶⁸Ga on a cyclotron, via the ⁶⁸Zn(p,n)⁶⁸Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced ⁶⁸Ga, extraction of [⁶⁸Ga]GaCl3 and subsequent [⁶⁸Ga]Ga-PSMA-11 labeling using an automated synthesis module. Methods: Irradiations of a 1.0 M solution of [⁶⁸Zn]Zn(NO3)2 i...
Article
Advances in drug discovery and diverse radiochemical methodologies have led to the discovery of novel positron emission tomography (PET) radiotracers used to image the GABAergic system, shaping our fundamental understanding of a variety of brain health illnesses, including epilepsy, stroke, cerebral palsy, schizophrenia, autism, Alzheimer's disease...
Article
To celebrate the 50th anniversary of the founding of the SNMMI Technologist Section in 1970, the Radiopharmaceutical Sciences Council board of directors is pleased to contribute to this celebratory supplement of the Journal of Nuclear Medicine Technology with a perspective highlighting major developments in the radiopharmaceutical sciences that hav...
Article
Purpose: Copper-mediated radiofluorination (CMRF) is emerging as the method of choice for the formation of aromatic C-18F bonds. This minireview examines proof-of-concept, pre-clinical, and in-human imaging studies of new and established imaging agents containing aromatic C-18F bonds synthesized with CMRF. An exhaustive discussion of CMRF methods...
Article
PD-132301, an inhibitor of sterol O-acyltransferase 1 (SOAT1; also known as acyl-coenzyme A:cholesterol acyltransferase 1, ACAT1), is under clinical investigation for numerous adrenal disorders. Radiolabelled SOAT1 inhibitors could support drug discovery and help diagnose SOAT1-related disorders, such as atherosclerosis. We synthesised two radiolab...
Article
[18F]-labeled aryl fluorides are widely used as radiotracers for positron emission tomography (PET) imaging. Aryl halides (ArX) are particularly attractive precursors to these radiotracers, as they are readily available, inexpensive, and stable. However, to date, the direct preparation of [18F]-aryl fluorides from aryl halides remains limited to SN...
Article
[18F]6-fluoro-l-DOPA ([18F]FDOPA) is a diagnostic radiopharmaceutical for positron emission tomography (PET) imaging that is used to image Parkinson’s disease, brain tumors, and focal hyperinsulinism of infancy. Despite these important applications, [18F]FDOPA PET remains underutilized because of synthetic challenges associated with accessing the r...
Article
The diaryl sulfonylurea MCC950/CRID3 is a potent NLRP3 inhibitor (IC50 = 8 nM) and, in animal models, MCC950 protects against numerous NLRP3-related neurodegenerative disorders. To evaluate the brain uptake and investigate target engagement of MCC950, we synthesised [¹¹C-urea]MCC950 via carrier added [¹¹C]CO2 fixation chemistry (activity yield = 23...
Article
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Welche C‐H‐Bindung? Die Ir‐katalysierte C‐H‐Borylierung ist eine effiziente Methode zur Synthese aromatischer Organoboronsäureester. Sterisch kontrollierte Regioselektivität dominiert die aromatische C‐H‐Borylierung bei Carbocyclen, dagegen zeigen Heterocyclen einen größeren Einfluss elektronischer Effekte. Dieser Aufsatz gibt Beispiele für C‐H‐Bor...
Article
Full-text available
Over the past twenty years, the iridium catalysed borylation of aromatic C‐H bonds has become the method for the synthesis of aromatic organoboron compounds required for many purposes including applications in natural product synthesis, material science, and medicinal chemistry. The reaction is highly efficient, tolerant of a broad range of substit...
Article
Full-text available
Naloxone (NLX) is a mu receptor antagonist used to treat acute opioid overdoses. Currently approved doses of naloxone to treat opioid overdoses are 4 mg intranasal (IN) and 2 mg intramuscular (IM). However, higher mu receptor occupancy (RO) may be required to treat overdoses due to more potent synthetic opioids such as fentanyl and carfentanil that...
Article
Full-text available
It is a growing concern that outcomes of neuroimaging studies often cannot be replicated. To counteract this, the magnetic resonance (MR) neuroimaging community has promoted acquisition standards and created data sharing platforms, based on a consensus on how to organize and share MR neuroimaging data. Here, we take a similar approach to positron e...