Jonathan Mcconathy

• University of Alabama Medical Center

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case–control...

Objective: To assess the presence of brain and systemic inflammation in subjects newly diagnosed with Parkinson's disease (PD). Background: Evidence for a pathophysiologic role of inflammation in PD is growing. However, several key gaps remain as to the role of inflammation in PD, including the extent of immune activation at early stages, potent...

Binding of 18F‐Flortaucipir (FTP) has qualitatively been noted in the skull. We investigate the characteristics of this off‐target signal, as well as its impact on regional PET analyses. FTP tau PET, 18F‐Florbetapir (FBP) amyloid PET, head CT, and T1‐weighted MR images were acquired for 313 cognitively unimpaired and impaired older participants. A...

Binding of 18F‐Flortaucipir (FTP) has qualitatively been noted in the skull. We investigate the characteristics of this off‐target signal, as well as its impact on regional PET analyses. FTP tau PET, 18F‐Florbetapir (FBP) amyloid PET, head CT, and T1‐weighted MR images were acquired for 313 cognitively unimpaired and impaired older participants. A...

Objective To assess the presence of brain and systemic inflammation in subjects newly diagnosed with Parkinson’s disease (PD). Background Evidence for a pathophysiologic role of inflammation in PD is growing. However, several key gaps remain as to the role of inflammation in PD, including the extent of immune activation at early stages, potential...

The Dominantly Inherited Alzheimer Network (DIAN) Observational Study is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). This rare form of Alzheimer disease (AD) is caused by mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. As individuals from these families...

PET/MR imaging is in routine clinical use and is at least as effective as PET/CT for oncologic and neurologic studies with advantages with certain PET radiopharmaceuticals and applications. In addition, whole body PET/MR imaging substantially reduces radiation dosages compared with PET/CT which is particularly relevant to pediatric and young adult...

Rationale: Measuring amyloid and predicting tau status using a single amyloid positron emission tomography (PET) study would be valuable for assessing brain AD pathophysiology. We hypothesized that early-frame amyloid PET (efAP) correlates with the presence of tau pathology because the initial regional brain concentrations of radioactivity are prim...

Objectives Primary brain tumors are composed of tumor cells, neural/glial tissues, edema, and vasculature tissue. Conventional MRI has a limited ability to evaluate heterogeneous tumor pathologies. We developed a novel diffusion MRI-based method—Heterogeneity Diffusion Imaging (HDI)—to simultaneously detect and characterize multiple tumor pathologi...

Background Tools for efficient evaluation of amyloid- and tau-PET images are needed in both clinical and research settings. Objective This study was designed to validate a semi-automated image analysis methodology, called Biomarker Localization, Analysis, Visualization, Extraction, and Registration (BLAzER). We tested BLAzER using two different se...

These joint practice guidelines, or procedure standards, were developed collaboratively by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the working group for Response Assessment in Neurooncology with PET (PET-RANO). Brain PET...

Rational: In a subset of cancers, arginine auxotrophy occurs due to the loss of expression of argininosuccinate synthetase 1 (ASS1). This loss of ASS1 expression makes cancers sensitive to arginine starvation that is induced by PEGylated arginine deiminase (ADI-PEG20). Although ADI-PEG20 treatment is effective, it does have important limitations. A...

PET/MRI has significant potential advantages over PET/CT for use in pediatric populations including decreasing radiation dose, reducing exposure to sedation and anesthesia, reducing the need for gadolinium-based MR contrast agents, and increasing convenience to children and their families through combining PET and MRI acquisition into a single imag...

Positron-emission tomography (PET) is a cross-sectional imaging technique that uses compounds labeled with positron-emitting radionuclides to measure the concentration and location of the radiolabeled compounds over time. PET has been used for a broad range of biomedical research and is used routinely in clinical patient care for oncologic, neurolo...

Amyloid-b (Ab) is ubiquitous in the central nervous system (CNS), but pathologic accumulation of Ab results in four distinct neurologic disorders that affect middle-aged and elderly adults, with diverse clinical presentations ranging from chronic debilitating dementia to acute life-threatening intracranial hemorrhage. The characteristic imaging pat...

Background: Noninvasively predicting early response to therapy in recurrent pediatric brain tumors provides a challenge. 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) PET/MRI has not been previously studied as a tool to evaluate early response to antiangiogenic therapy in children. The purpose of this study was to evaluate the safety and...

This joint statement is intended to guide credentialing bodies that privilege physicians to oversee the performance of and participation in the interpretation of PET/MR imaging in adult and pediatric patients in the United States.

Background Whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard of care for lymphoma. Simultaneous PET/MRI (magnetic resonance imaging) is a promising new modality that combines the metabolic information of PET with superior soft-tissue resolution and functional imaging capabilities of MR...

Hybrid imaging with integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) combines the advantages of the high-resolution anatomic data from MRI and functional imaging data from PET, and has the potential to improve the diagnostic evaluation of various types of cancers. The clinical oncologic applications of this newest...

Importance: In vivo tau imaging may become a diagnostic marker for Alzheimer disease (AD) and provides insights into the pathophysiology of AD. Objective: To evaluate the usefulness of [18F]-AV-1451 positron emission tomography (PET) imaging to stage AD and assess the associations among β-amyloid (Aβ), tau, and volume loss. Design, setting, and...

View largeDownload slide Tau pathology is a hallmark of Alzheimer’s disease but until recently could only be measured in cerebrospinal fluid. Using PET, Gordon et al. demonstrate elevated tau deposition in medial temporal, parietal, and medial prefrontal cortex in individuals with dementia. PET tracer uptake strongly correlates with tauopathy meas...

Amyloid-β (Aβ) is ubiquitous in the central nervous system (CNS), but pathologic accumulation of Aβ results in four distinct neurologic disorders that affect middle-aged and elderly adults, with diverse clinical presentations ranging from chronic debilitating dementia to acute life-threatening intracranial hemorrhage. The characteristic imaging pat...

https://deepblue.lib.umich.edu/bitstream/2027.42/153280/1/alzjjalz201606709.pdf

Hybrid imaging with integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) combines the advantages of the high-resolution anatomic data from MRI and functional imaging data from PET, and has the potential to improve the diagnostic evaluation of various types of cancers. The clinical oncologic applications of this newest...

Two [(18)F]fluoroalkyl substituted amino acids differing only by the presence or absence of a methyl group on the α-carbon, (S)-2-amino-7-[(18)F]fluoro-2-methylheptanoic acid ((S)-[(18)F]FAMHep, (S)-[(18)F]14), and (S)-2-amino-7-[(18)F]fluoroheptanoic acid ((S)-[(18)F]FAHep, (S)-[(18)F]15), were developed for brain tumor imaging and compared to the...

Background: Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has become the standard of care for the initial staging and subsequent treatment response assessment of many different malignancies. Despite this success, PET/CT is often supplemented by MRI to improve assessment of local tumor invasion...

Background Because standard MRI-based attenuation correction (AC) does not account for the attenuation of photons by cortical bone, PET/MRI may have reduced sensitivity for FDG-avid focal bone lesions (FFBLs). This study evaluates whether MRI-based AC compromises detection of FFBLs, by comparing their conspicuity both quantitatively and qualitative...

Methods: Florbetapir scans were obtained on 40 participants on a Biograph mMR hybrid scanner with simultaneous MR acquisition. PET images were reconstructed using both MR and CT derived attenuation map. Quantitative analysis was performed for both datasets to assess the impact of MR based attenuation correction to absolute PET activity measurement...

Positron emission tomography (PET), commonly performed in conjunction with computed tomography (CT), has revolutionized oncologic imaging. PET/CT has become the standard of care for the initial staging and assessment of treatment response for many different malignancies. Despite this success, PET/CT is often supplemented by magnetic resonance imagi...

Background: Simultaneous acquisition Positron emission tomography/magnetic resonance (PET/MR) is a new technology that has potential as a tool both in research and clinical diagnosis. However, cardiac PET acquisition has not yet been validated using MR imaging for attenuation correction (AC). The goal of this study is to evaluate the feasibility o...

The novel compound, (S)-amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic acid (BrVAIB, [(76)Br]5), was characterized against the known system A tracer, IVAIB ([(123)I]8). [(76)Br]5 was prepared in a 51% ± 19 % radiochemical yield with high radiochemical purity (> 98%). The biological properties of [(76)Br]5 were compared with [(123)I]8. Results showed...

Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG), is a hallmark of active cancer cells that is not directly measured with standard 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET). In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucos...

Dementia due to Alzheimer’s disease (AD) is the result of pathological changes which begin years or even decades before the onset of symptoms. The accumulation of beta amyloid (Aβ) in plaques and tau protein in tangles plays an important role in disease progression. Individuals with significant Aβ plaques, as measured with positron emission tomogra...

A novel (18)F-labeled α,α-disubstituted amino acid-based tracer, 2-amino-5-[(18)F]fluoro-2-methylpentanoic acid ([(18)F]FAMPe) has been developed for brain tumor imaging with a longer alkyl side chain than previously reported compounds to increase brain availability via system L amino acid transport. Both enantiomers of [(18)F]FAMPe were obtained i...

The purpose of this pictorial review is to describe emerging clinical applications of positron emission tomography (PET)/magnetic resonance imaging (MRI), the newest clinical hybrid imaging modality, with a specific focus on abdominal and pelvic malignancies. Important issues regarding the clinical implementation of PET/MRI systems, including workf...

Founded in 1951, the Joint Commission, formerly known as the Joint Commission on Accreditation of Healthcare Organizations and, previous to that, the Joint Commission on Accreditation of Hospitals, is a United States–based nonprofit organization that accredits more than 20,000 health care organizations and programs in the United States. The Joint C...

In evaluating disease changes, it is critical to have measurements that are sensitive, specific, and reliable. Cognitive decline, particularly in the context of Alzheimer's disease, is an area that has attracted numerous recent studies, and the proposed biomarkers used in these investigations need to be validated. In this review, we highlight studi...

PET/MRI is a hybrid imaging modality that is gaining clinical interest with the first Food and Drug Administration-approved simultaneous imaging system recently added to the clinical armamentarium. Several advanced PET/MRI applications, such as high-resolution anatomic imaging, diffusion-weighted imaging, motion correction, and cardiac imaging, sho...

Introduction: Amino acid based radiotracers target tumor cells through increased uptake by membrane-associated amino acid transport (AAT) systems. In the present study, four structurally related non-natural (18)F-labeled amino acids, (R)- and (S)-[(18)F]FAMP 1 and (R)- and (S)-[(18)F]MeFAMP 2 have been prepared and evaluated in vitro and in vivo f...

Objectives Positron emission tomography (PET) has been used to assess the active tumor growth and treatment effects in many neoplasms including primary and metastatic brain tumors. Traditionally, this has been accomplished by measuring total glucose utilization assuming that this is an adequate reflection of the tumor growth and progression. Howeve...

PET/MR offers potential advantages over PET/CT that are currently under investigation. One of the challenges of PET/MR is attenuation correction, as there is no simple correlation between MR signal intensity and the attenuation of 511-keV photons detected in PET. Currently, dedicated MR sequences are used to segment voxels into categories that are...

The purpose of this article is to introduce the underlying challenges associated with the incorporation of magnetic resonance imaging (MRI) into the new hybrid imaging modality simultaneous positron emission tomography (PET)/MR and their impact on attenuation correction, sequence optimization, and protocol development. Many adjustments to MR sequen...

Several double blind, prospective trials have demonstrated an antidepressant augmentation efficacy of aripiprazole in depressed patients unresponsive to standard antidepressant therapy. Although aripiprazole is now widely used for this indication, and much is known about its receptor-binding properties, the mechanism of its antidepressant augmentat...

Objective: The objective of this article is to describe an approach to imaging CSF shunts. Topics reviewed include the components and imaging appearances of the most common types of shunts and the utility of different imaging modalities for the evaluation of shunt failure. Complications discussed include mechanical failure, infection, ventricular...

PURPOSE/AIM 1. Review the pathophysiology of diffusion restriction and FDG uptake in osseous metastases. 2. Illustrate the appearance of multiple myeloma (MM), lymphoma, and bone metastases on MRI/DWI, FDG-PET/CT, fluoride-PET/CT, FDG-PET/MR, and MDP bone scintigraphy. 3. Describe the correlation between the different modalities and their use as no...

PURPOSE MR attenuation correction (MRAC) in hybrid PET/MR imaging poses challenges for accurate quantification. CT attenuation correction (CTAC) provides an approximation of mass attenuation based on tissue density. To assess the accuracy of factory MRAC methods, two methods were compared to CTAC for a series of patients that had PET/CT and PET/MR...

LEARNING OBJECTIVES 1) Describe the PET tracers in late phase clinical trials for oncologic imaging in terms of their molecular targets and potential clinical indications. 2) Identify the major regulatory and financial challenges encountered during the translation of PET tracers into widespread clinical use. 3) Compare the properties, strengths, an...

PURPOSE To quantify and compare the cerebral oxygen extraction fraction (OEF) measurement in the normal brain and brain tumors using 15O positron emission tomography (PET) and oxygen sensitive magnetic resonance (MR)1,2 imaging. METHOD AND MATERIALS 30 participants (20 with brain tumors) were recruited. MRI included standard clinical sequences pl...

The diagnosis of Alzheimer disease (AD) dementia is based primarily on the clinical history and examination, but advances in understanding the pathophysiology of AD have led to new diagnostic methods. When used appropriately, the tests can provide strong positive or negative evidence AD dementia. This article described which patients may benefit fr...

This chapter reviews important considerations for the performance and interpretation of [18F]fluorodeoxyglucose (FDG)-PET/CT in the diagnostic evaluation of patients with esophageal cancer. Accurate staging is the primary basis for selecting appropriate treatment for patients with esophageal cancer. Attention to patient preparation, imaging protoco...

The L-type amino acid transporter-1 (LAT1, SLC7A5) is upregulated in a wide range of human cancers, positively correlated with the biological aggressiveness of tumors, and a promising target for both imaging and therapy. Radiolabeled amino acids such as O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) that are transport substrates for system L amino acid...

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Sulforaphane (SFN) and beta-phenylethyl isothiocyanate (PEITC), are organic isothiocyanate compounds found in dietary cruciferous vegetables with previously characterized anti-proliferative properties; and more recently, pro-apoptosis capabilities in several tumor types. T...

Radiolabeled amino acids (AAs) are an important class of imaging agents for PET and SPECT that target the increased levels of AA transport by many tumor cells. System L AA transport has been a major focus of tracer development, and work in this field has led to several tracers that are effective for imaging brain tumors. Emerging data also support...

Unlabelled: The goal of this study was to evaluate the (18)F-labeled nonnatural amino acid (S)-2-amino-3-[1-(2-(18)F-fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid ((18)F-AFETP) as a PET imaging agent for brain tumors and to compare its effectiveness with the more-established tracers O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) and (18)F-FDG...

18F-labeled amino acids are an important class of imaging agents for positron emission tomography (PET) that target the increased rates of amino acid transport by many tumor cells. This class of tracers is structurally diverse, and the biological and imaging properties of a given 18F-labeled amino acid depends largely upon its mechanism of transpor...

This article provides an overview of the key considerations for the development and application of molecular imaging agents for brain tumors and the major classes of PET tracers that have been used for imaging brain tumors in humans. The mechanisms of uptake, biological implications, primary applications, and limitations of PET tracers in neuro-onc...

Objectives: Radiolabeled amino acids have proven utility for imaging brain tumors in humans, particularly those that target system L amino acid transport. We have prepared the novel phenylalanine analogue, (FMePhe, 9), as part of an effort to develop new system L tracers that can be prepared in high radiochemical yield through nucleophilic [(18)F]...

Nuclear medicine imaging provides valuable functional information that complements information obtained with anatomic imaging techniques in the evaluation of patients with specific acute clinical manifestations. Nuclear medicine studies are most often used in conjunction with other imaging modalities and as a problem-solving tool. Under certain cir...

Background Simultaneous acquisition PET-MRI is a new technology that has the potential to significantly impact diagnostic patient care. Cardiac imaging using PET-MRI offers high signal resolution MRI images superimposed on PET metabolic functional assessment. Specifically, 18Ffluorodeoxyglucose (FDG) PET-MR has the potential to provide both anatomi...

PURPOSE This study compares the diagnostic performance of simultaneous positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and magnetic resonance imaging (PET/MR) to conventional PET/CT in patients with proven head and neck malignancies with a focus on skull base and oral cavity disease sites in order to establish the utility o...

PURPOSE To quantify and compare the cerebral oxygen extraction fraction (OEF) measurement in the normal brain and brain tumors using 15O positron emission tomography (PET) and magnetic resonance(MR)1,2 imaging. Tumor hypoxia has been associated with sensitivity to radiation therapy, gene expression, and prognosis, but has not been widely studied in...

PURPOSE The radiolabeled histidine analogue AFETP, with promising preclinical tumor imaging properties, is a substrate for cationic amino acid transport in vitro. To further develop this novel non-natural amino acid series for PET tumor imaging, we synthesized a novel AFETP analogue, (S)-2-amino-3-[1-(2-[18F]fluoroethyl)-1H-[1,2,3]triazol-4-yl]hexa...

PURPOSE Improved imaging techniques are needed to reliably distinguish viable tumor from radiation effects for neuro-oncology patients. This study compared the uptake and kinetics of three 18F-labeled amino acids and FDG in mice with intracranial DBT gliomas and Gamma Knife induced radiation lesions to assess their utility for distinguishing these...

PURPOSE To assess focal activity associated with suspected meningiomas observed on 11C-labeled Pittsburgh Compound B (PiB) PET studies. METHOD AND MATERIALS We have performed 1000 PiB PET studies from 2000 to 2012 to evaluate brain beta-amyloid levels in healthy controls and subjects with dementia. All subjects with PiB studies also underwent brai...

PURPOSE To evaluate the clinical utility of simultaneous acquisition of PET and MR imaging in patients with gynecologic malignancies and to compare PET/MR images with those obtained with PET/CT. METHOD AND MATERIALS Integrated whole-body PET/MR imaging was acquired for 18 patients with gynecologic malignancies using the Siemens Biograph mMR system...

Radiohalogenated α-amino acids are a diverse and useful class tumor imaging agents suitable for positron emission tomography and single photon emission computed tomography. These tracers target the increased rates of amino acid transport exhibited by many tumor cells. The most established clinical use for radiolabeled amino acids is imaging primary...

The (R)- and (S)-enantiomers of 2-amino-3-[1-(2-[18F]fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid (4) were synthesized and evaluated in the rat 9L gliosarcoma brain tumor model using cell uptake assays, biodistribution studies, and micro-positron emission tomography (microPET). The (R)- and (S)-enantiomers of [18F]4 were radiolabeled separate...

The non-natural amino acids (R)- and (S)-2-amino-3-fluoro-2-methylpropanoic acid 5 and (R)- and (S)-3-fluoro-2-methyl-2-N-(methylamino)propanoic acid 8 were synthesized in shorter reaction sequences than in the original report starting from enantiomerically pure (S)- and (R)-alpha-methyl-serine, respectively. The reaction sequence provided the cycl...

Amino acids are required nutrients for proliferating tumor cells, and amino acid transport is upregulated in many tumor types. Studies of radiolabeled amino acids in animals and humans demonstrate that amino acid based tracers have advantageous characteristics relative to 2-[(18)F]fluoro-2-deoxyglucose in certain tumors, particularly brain gliomas....

Both enantiomers of 2-amino-2-methyl-4-iodo-3-(E)-butenoic acid (IVAIB, 5) were radioiodoinated in 65-72% yield. (S)-IVAIB entered 9L gliosarcoma cells primarily via A-type transport in vitro with higher uptake than (R)-IVAIB. Biodistribution studies in rats with 9L gliosarcoma brain tumors demonstrated higher tumor to brain ratios with (S)-IVAIB (...

Obtaining drugs for use in basic and preclinical research has become increasingly difficult and in many instances is dependent upon the company's interest in the proposed research. In this paper, we describe a simple procedure for extracting the antidepressants sertraline, paroxetine, fluoxetine, venlafaxine, citalopram, escitalopram, duloxetine an...

The nortropane cocaine analogue, 2beta-carbomethoxy-3beta-[4'-((Z)-2-iodoethenyl)phenyl]nortropane (ZIENT), is a high affinity, selective serotonin transporter (SERT) ligand that has shown promise as a SERT imaging agent for single photon computed tomography (SPECT) when labeled with I-123. Synthesis of the labeling precursor, radiosynthesis of [(1...

The fluorine-18 labeled dopamine transport (DAT) ligand 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (FECNT) has shown promising properties as an in vivo DAT imaging agent in human and monkey PET studies. A semi-automated synthesis has been developed to reliably produce [F-18]FECNT in a 16% decay corrected yield. This met...

The development of radioligands suitable for studying the central nervous system (CNS) norepinephrine transporter (NET) in vivo will provide important new tools for examining the pathophysiology and pharmacotherapy of a variety of neuropsychiatric disorders including major depression. Towards this end, a series of trans-3-phenyl-1-indanamine deriva...