Peter Scott

• BSc, PhD
• Managing Director at University of Michigan

The prevalence of neuroendocrine neoplasms (NEN), which include neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC), has increasing during recent years. The approval of diagnostic single-photon emission computed tomography and positron emission tomography imaging agents for NEN is an important factor in pushing the development of additi...

Theranostics represents the state-of-the-art in precision oncology treatment, and is gaining momentum because of the potential to help improve outcomes for even late-stage cancer patients. Pairs of identical (or very similar) molecules are labeled with both diagnostic and therapeutic radionuclides, and used to both image and treat cancer. The FDA a...

The carbon‐11 (¹¹C) labeling of benzamides holds great promise in the development of PET radiotracers given the prevalence of benzamides in bioactive molecules. This work establishes an improved automated route to ¹¹C labeled primary benzamides through carbonylative cross‐coupling of aryl halides with ¹¹C carbon monoxide using electrophilic aroyl d...

Background Approval of Locametz and Illuccix kits for the manufacture of [68Ga]Ga-PSMA-11 (gallium Ga68 gozetotide), a PET imaging agent for prostate cancer, as well as the corresponding therapeutic ([177Lu]Lu-PSMA-617 Pluvicto), has led to a rapid increase in demand for [68Ga]Ga-PSMA-11 PET imaging. Radiopharmaceutical manufacturers, using 68Ge/68...

Background Approval of Locametz and Illuccix kits for the manufacture of [⁶⁸Ga]Ga-PSMA-11 (gallium Ga68 gozetotide), a PET imaging agent for prostate cancer, as well as the corresponding therapeutic ([¹⁷⁷Lu]Lu-PSMA-617 Pluvicto), has led to a rapid increase in demand for [⁶⁸Ga]Ga-PSMA-11 PET imaging. Radiopharmaceutical manufacturers, using ⁶⁸Ge/⁶⁸...

The success of multiple nuclear medicine radiotherapeutics in treating cancer requires an increased supply of companion diagnostic imaging agents radiolabeled with gallium-68. Cyclotron production addresses the need for access to gallium-68 and has been validated for use with commercially produced sterile kits. For novel research tracers undergoing...

Background Approval of Locametz and Illuccix kits for the manufacture of [ ⁶⁸ Ga]Ga-PSMA-11 (gallium Ga68 gozetotide), a PET imaging agent for prostate cancer, as well as the corresponding therapeutic ([ ¹⁷⁷ Lu]Lu-PSMA-617 Pluvicto), has led to a rapid increase in demand for [ ⁶⁸ Ga]Ga-PSMA-11 PET imaging. Radiopharmaceutical manufacturers, using ⁶...

Circulating monocytes infiltrate and coordinate immune responses in tissues surrounding implanted biomaterials and in other inflamed tissues. Here we show that immunometabolic cues in the biomaterial microenvironment govern the trafficking of immune cells, including neutrophils and monocytes, in a manner dependent on the chemokine receptor 2 (CCR2)...

Background Postural instability and gait disturbances (PIGD) represent a significant cause of disability in Parkinson's disease (PD). Cholinergic system dysfunction has been implicated in falls in PD. The occurrence of falls typically results in fear of falling (FoF) that in turn may lead to poorer balance self-efficacy. Balance self-efficacy refer...

The cholinergic system has been implicated in postural deficits, in particular falls, in Parkinson’s disease. Falls and freezing of gait typically occur during dynamic and challenging balance and gait conditions, such as when initiating gait, experiencing postural perturbations, or making turns. However, the precise cholinergic neural substrate und...

Fluorine-18 is the most routinely employed radioisotope for positron emission tomography, a dynamic nuclear imaging modality. The radiolabeling of C–H bonds is an attractive method for installing fluorine-18 into organic molecules since it can preclude the cumbersome prefunctionalization of requisite precursors. Although electrophilic “F⁺” reagents...

The most prominent myocardial voltage-gated sodium channel, NaV1.5, is a major drug target for treating cardiovascular disease. However, treatment determination and therapeutic development are complicated partly by an inadequate understanding...

Copper-mediated radiolabelling has revolutionised how (hetero)aromatic imaging agents are prepared for positron emission tomography (PET). Despite advancements, this radiochemistry fails to address critical stability, reactivity, and toxicity concerns encountered in many labelling systems, which are paramount for safely and reproducibly generating...

Background: Cancer-associated fibroblasts have become a new target for therapy. Fibroblasts present within malignancies express the fibroblast activation protein (FAP). Inhibitors to FAP (FAPI) are small molecules recently developed as a theranostic agents for imaging and radiotherapy. All currently used FAPI rely on a linker–chelator complex attac...

A new automated radiosynthesis of [ ¹¹ C]2‐(2,6‐difluoro‐4‐((2‐( N ‐methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([ ¹¹ C]K2), a radiopharmaceutical for the glutamate α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor, is reported. Although manual syntheses have been described, these are unsuitable for routine production o...

This meeting report summarizes a consultants meeting that was held at International Atomic Energy Agency Headquarters, Vienna, in July 2022 to provide an update on the development of multimodality imaging by combining nuclear medicine imaging agents with other nonradioactive molecular probes and/or biomedical imaging techniques.

This article is intended to introduce nuclear medicine technologists (NMTs) to the nuances of radiopharmaceutical therapy clinical trials. Here, we outline the potential roles and responsibilities of the NMT in clinical trials and provide context on different aspects of radionuclide therapy. The regulatory process involving investigational therapeu...

Flumazenil is an allosteric modulator of the γ-aminobutyric acid-A receptor (GABAAR) benzodiazepine binding site that could normalize neuronal signaling and improve motor impairments in Parkinson’s disease (PD). Little is known about how regional GABAAR availability affects motor symptoms. We investigated the relationship between regional availabil...

Direct C–H functionalization of (hetero)aromatic C–H bonds with iridium-catalyzed borylation followed by copper-mediated radiofluorination of the in situ generated organoboronates affords fluorine-18 labeled aromatics in high radiochemical conversions and meta-selectivities. This protocol describes the benchtop reaction assembly of the C–H borylati...

Recent developments in 68Ga-radiopharmaceuticals, including a number of regulatory approvals for clinical use, has created a hitherto unprecedented demand for 68Ga. Reliable access to enough 68Ga to meet growing clinical demand using only 68Ge/68Ga generators has been problematic in recent years. To address this challenge, we have optimized the dir...

Recent Food and Drug Administration (FDA) approval of diagnostic and therapeutic radiopharmaceuticals and concurrent miniaturization of particle accelerators leading to improved access has fueled interest in the development of chemical transformations suitable for short-lived radioactive isotopes on the tracer scale. This recent renaissance of radi...

The International Atomic Energy Agency (IAEA) held the 3rd International Symposium on Trends in Radiopharmaceuticals, (ISTR-2023) at IAEA Headquarters in Vienna, Austria, during the week of 16–21 April 2023. This procedural paper summarizes highlights from symposium presentations, posters, panel discussions and satellite meetings, and provides addi...

Preclinical or non-clinical evaluation is an integral part of the development of any drug. The process of developing a new radiopharmaceutical includes rigorous testing before it can be cleared for use in humans. In-depth characterization of its behaviour is necessary to assess its safety and suitability for the intended clinical application. This...

This report describes a net C–H radiocyanation reaction for the transformation of electron rich (hetero)aromatic substrates into ¹¹CN-labeled products. Electrophilic C(sp²)–H iodination of the (hetero)arene with N-iodosuccinimide is followed by Cu-mediated radiocyanation with K¹¹CN. This sequence is applied to a variety of substrates, including the...

An in-loop 11 C-carbonylation process for the radiosynthesis of 11 C-carboxylic acids and esters from halide precursors has been developed. The reaction proceeds at room temperature under mild conditions and enables 11 C-carbonylation of both electron deficient and electron rich (hetero)aromatic halides to provide 11 C-carboxylic acids and esters i...

Objective The current understanding of utilizing HD-tDCS as a targeted approach to improve headache attacks and modulate endogenous opioid systems in episodic migraine is relatively limited. This study aimed to determine whether high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) can improve clinical...

Positron emission tomography (PET) is a powerful tool in medicine and drug development, allowing for non-invasive imaging and quantitation of biological processes in live organisms. Targets are often probed with small molecules, but antibody-based PET is expanding because of many benefits, including ease of design of new antibodies toward targets,...

Postural instability and freezing of gait are the most debilitating dopamine-refractory motor impairments in advanced stages of Parkinson’s disease because of increased risk of falls and poorer quality of life. Recent findings suggest an inability to efficaciously utilize vestibular information during static posturography among people with Parkinso...

Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main Body This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety...

Radiocyanation is an attractive strategy for incorporating carbon-11 into radiotracer targets, particularly given the broad scope of acyl moieties accessible from nitriles. Most existing methods for aromatic radiocyanation require elevated temperatures (Cu-mediated reactions of aryl halides or organometallics) or involve expensive and toxic palladi...

This report describes a comparison of four different routes for the clinical-scale radiosynthesis of the κ-opioid receptor antagonist [11C]LY2795050. Palladium-mediated radiocyanation and radiocarbonylation of an aryl iodide precursor as well as copper-mediated radiocyanation of an aryl iodide and an aryl boronate ester have been investigated. Full...

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...

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...

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...

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...

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...

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...

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...

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...

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 ¹⁸F radiotracer for MC-I enables monitoring of neurodegenerative disease progression and pathology via PET imaging. To facilitate clinical research studies tracking MC-I...

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...

[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...

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...

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),...

Mutations in the huntingtin gene (HTT) triggers aggregation of huntingtin protein (mHTT), which is the hallmark pathology of neurodegenerative Huntington’s disease (HD). Development of a high affinity ¹⁸F radiotracer would enable the study of Huntington’s disease pathology using a non-invasive imaging modality, positron emission tomography (PET) im...

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...

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...

[¹¹C]Verubulin (a.k.a.[¹¹C]MCP-6827), [¹¹C]HD-800 and [¹¹C]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 [¹¹C]verubulin for MT imaging in mouse and rat brain, as well as an in vitro study with this radiotracer in rodent and hu...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...