Julie C. Price | |
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![]() Price in 2019 | |
Nationality | American |
Alma mater | University of Wisconsin-Madison Johns Hopkins University National Institutes of Health |
Known for | Pharmacokinetic analyses of PIB PET ligand |
Awards | 2016 Alavi–Mandell Award |
Scientific career | |
Fields | Radiology, Physics |
Institutions | Harvard Medical School |
Julie C. Price is an American medical physicist and professor of radiology at Massachusetts General Hospital (MGH), Harvard Medical School (HMS), as well as the director of PET Pharmacokinetic Modeling at the Athinoula A. Martinos Center at MGH. Price is a leader in the study and application of quantitative positron emission tomography (PET) methods. Prior to this, Price worked with Pittsburgh colleagues (Mathis and Klunk) to lead the first fully quantitative pharmacokinetic evaluations of 11C-labeled Pittsburgh compound-B (PIB), one of the most widely used PET ligands for imaging amyloid beta plaques. As a principal investigator at MGH, Price continues work to validate novel PET methods for imaging biological markers of health and disease in studies of aging and neurodegeneration, including studies of glucose metabolism, protein expression, neurotransmitter system function, and tau and amyloid beta plaque burden.
Price attended the University of Wisconsin-Madison for her undergraduate degree. [1] She majored in physics and graduated with a Bachelor of Science in 1982 [1] with key encouragement from Professor Converse Blanchard. Upon completion of her bachelors, Price stayed at the University of Wisconsin-Madison to pursue her master's in medical physics [1] under the mentorship of Professor John Cameron. She worked in the Radiation Calibration Service as a project specialist during her Master's where she explored the efficacy of diode dosimeters used to monitor radiotherapy doses. [2] In 1985, during her Master's training, Price worked as a Summer Physics Research Assistant in the Diagnostic Radiology Department at the Mayo Clinic in Rochester, Minnesota, [1] learning to assess the level of radiation exposure to the fetus from multislice CT scans. [3]
As a Medical Physicist at George Washington University (1986), she had the opportunity to work with Drs. Reba, Gibson, and Zeeburg on kinetic modeling research. She then pursued her graduate studies at Johns Hopkins University within the School of Hygiene and Public Health in Baltimore, Maryland [1] in the Radiation Health Sciences Program, directed by Dr. Henry N. Wagner Jr. Her graduate advisors were Dr. J. James Frost and Dr. Jonathan Links. Her thesis work focused on quantification of opiate receptor and benzodiazepine receptor concentrations and affinity in vivo in the human brain using PET imaging and 11C-Diprenorphine [4] and 11C-flumazenil, [5] respectively. She later took part in a Yale-JHU collaboration to use Single Photon Emission Tomography to measure Benzodiazepine receptor concentration and affinity in the brains of non-human primates using a constant infusion paradigm, led by Drs. Innis and Laruelle. [6]
Price then completed her postdoctoral work at the National Institutes of Health in the Department of PET and Nuclear Medicine. As a National Research Council fellow under the supervision of Drs. Richard Carson and Stephen Bacharach. She helped to implement a novel method to reduce the transmission noise in 18F-FDG cardiac emission images, [7] based on the use of a model that sharpens the peaks of the measured attenuation histograms of the images to minimize noise. [7]
Following her postdoctoral training, Price was recruited to the University of Pittsburgh in 1994 as a PET physicist and assistant professor in the PET Facility and Department of Radiology at the University of Pittsburgh Medical Center. [8] In 2002, Price was promoted to associate professor and served as Head of PET Methodology at the University of Pittsburgh PET facility, a position she held until 2016. [9] She was awarded tenure in 2006 and promoted to full professor in the Department of Radiology in 2010 and secondarily in the Department of Biostatistics (2013). [1] She also led the Imaging, Methodology and Statistics Core of the Pittsburgh amyloid imaging program project grant (AG025204, Klunk PI) from 2005 to 2016. Over 35 NIH grantome entries are listed for Price, over a 14-year period, for PET imaging investigations of the pharmacokinetic properties of PET ligands and for clinical research applications in aging, neuropsychiatric disorders, and neurodegeneration. [10]
In 2016, Price became an Investigator in the Department of Radiology at the Massachusetts General Hospital, Director of PET Pharmacokinetic Modeling at the Athinoula A. Martinos Center for Biomedical Imaging, and Visiting Professor of Radiology at Harvard Medical School. [1] As Professor of Radiology (2017), she continued to pursue AD research with members of the Harvard Aging Brain Study (HABS) and Massachusetts Alzheimer's Disease Research Center. She uses her expertise in PET imaging to foster the development of novel methods to improve the early detection of AD through imaging of tau and amyloid beta plaque deposits. She continues to collaborate with her previous institutions including the Waisman Center at the University of Wisconsin-Madison [11] and the University of Pittsburgh through work done on the NIH Down Syndrome Consortium project or ABC-DS. [12] Price is also on the publication committee for the Journal of Cerebral Blood Flow and Metabolism, a leading journal in the field. [13]
As Principal Investigator of the Price Lab at the Martinos Center for Biomedical Imaging, her translational collaborations extend into other areas. [14] These projects include PET imaging to assess epigenetic changes in Huntington's Disease and Parkinson's Disease and developing novel diagnostic methods to measure pathological Tau deposition in the human brain through PET imaging. [15] Her research also addresses race-based differences in disease as she explores the mechanisms of altered peripheral glucose uptake in African American women. [15] She also supports efforts to apply PET imaging to assess the outcomes of meditation on chronic pain and migraines by tracking neuroinflammation using novel PET ligands. [15]
While at the University of Pittsburgh, Price's colleagues William E. Klunk and Chester A. Mathis developed 11C-labeled Pittsburgh compound-B (PiB) one of the first selective PET amyloid beta plaque imaging agents. [16] Price played an integral role in the kinetic evaluation of the Pittsburgh Compound B, and establishing its use for imaging amyloid beta plaques in living human brain. [17] [18] Price also took part in several follow-up studies to evaluate simplified methods and to confirm the optimal time window and experimental designs for use of PIB across the AD disease spectrum [19] and in those at high risk for early onset familial AD. [20] This work represents early critical steps that supported the use of PiB retention as a stable and valid in vivo marker of amyloid beta AD neuropathology and helped to establish this new and rapidly growing field of research.
Price's work then extended to PET imaging of tau burden in AD, with neurofibrillary tangles of hyperphosphorylated tau being another neuropathological hallmark of AD. [21] This includes a Pittsburgh neuropathological evaluation of “off-target” Flortaucipir (or 18F-AV-1451) retention in choroid plexus that confounds quantification of tau deposition in hippocampus [22] and a collaboration with University of California Berkeley colleagues to evaluate the regional kinetics of 18F-AV-1451 in aging and dementia. These studies contributed to a better understanding of “on-target” Flortaucipir retention in sub-cortical areas and late scan retention in high-binding individuals that can impact the accuracy and interpretation of longitudinal assessments. Other collaborative work includes efforts by HABS colleagues that include a 2019 study by Dr. Buckley that revealed that women had higher early tau deposition compared to men on an AD trajectory [23] and a 2021 research study that demonstrated initial emergence of the tau PET signal in mesial temporal lobe (MTL) on an individual basis, and MTL tau as a harbinger of future neocortical tau accumulation. [24]
In addition to neurodegeneration, Price helped to investigate vascular abnormalities in psychiatric disease using PET imaging. This includes early research with Dr. Meltzer at Pittsburgh to assess whether cerebral blood flow (CBF) is reduced in aging. [25] That revealed no decrease in CBF after correction of the PET signal for the dilutional effect of age-related atrophy and the impact of this correction on the accuracy of brain measurements. [25] Price's work with Dr. Kaye and colleagues explored changes in CBF in women with bulimia nervosa revealed an inverse relationship between the length of recovery and the level of CBF suggesting that CBF might be a predictor of recovery. [26]
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, regional chemical composition, and absorption. Different tracers are used for various imaging purposes, depending on the target process within the body.
Amyloid plaques are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve, with an average plaque area of 400-450 square micrometers (μm2). The smallest plaques, which often consist of diffuse deposits of Aβ, are particularly numerous. Plaques form when Aβ misfolds and aggregates into oligomers and longer polymers, the latter of which are characteristic of amyloid.
Pittsburgh compound B (PiB) is a radioactive analog of thioflavin T, which can be used in positron emission tomography scans to image beta-amyloid plaques in neuronal tissue. Due to this property, Pittsburgh compound B may be used in investigational studies of Alzheimer's disease.
Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Increasingly it is also being used for quantitative research studies of brain disease and psychiatric illness. Neuroimaging is highly multidisciplinary involving neuroscience, computer science, psychology and statistics, and is not a medical specialty. Neuroimaging is sometimes confused with neuroradiology.
Raclopride is a typical antipsychotic. It acts as a selective antagonist on D2 dopamine receptors. It has been used in trials studying Parkinson Disease.
The biochemistry of Alzheimer's disease, the most common cause of dementia, is not yet very well understood. Alzheimer's disease (AD) has been identified as a proteopathy: a protein misfolding disease due to the accumulation of abnormally folded amyloid beta (Aβ) protein in the brain. Amyloid beta is a short peptide that is an abnormal proteolytic byproduct of the transmembrane protein amyloid-beta precursor protein (APP), whose function is unclear but thought to be involved in neuronal development. The presenilins are components of proteolytic complex involved in APP processing and degradation.
Altanserin is a compound that binds to the 5-HT2A receptor. Labeled with the isotope fluorine-18 it is used as a radioligand in positron emission tomography (PET) studies of the brain, i.e., studies of the 5-HT2A neuroreceptors. Besides human neuroimaging studies altanserin has also been used in the study of rats.
DASB, also known as 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, is a compound that binds to the serotonin transporter. Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand in neuroimaging with positron emission tomography (PET) since around year 2000. In this context it is regarded as one of the superior radioligands for PET study of the serotonin transporter in the brain, since it has high selectivity for the serotonin transporter.
WAY-100635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at the D4 receptor. It is sometimes referred to as a silent antagonist at the former receptor. It is closely related to WAY-100135.
The partial volume effect can be defined as the loss of apparent activity in small objects or regions because of the limited resolution of the imaging system. It occurs in medical imaging and more generally in biological imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). If the object or region to be imaged is less than twice the full width at half maximum (FWHM) resolution in x-, y- and z-dimension of the imaging system, the resultant activity in the object or region is underestimated. A higher resolution decreases this effect, as it better resolves the tissue.
DAA-1106 is a drug which acts as a potent and selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO, but with no affinity at the GABAA receptor. It has anxiolytic effects in animal studies. DAA-1106 has a sub-nanomolar binding affinity (Ki) of 0.28 nM, and has been used extensively in its 3H or 11C radiolabelled form to map TSPO in the body and brain, which has proved especially helpful in monitoring the progress of neurodegenerative diseases such as Alzheimer's disease.
Avid Radiopharmaceuticals is an American company, founded by Dr. Daniel Skovronsky, and based at the University City Science Center research campus in Philadelphia, Pennsylvania. The company has developed a radioactive tracer called florbetapir (18F). Florbetapir can be used to detect beta amyloid plaques in patients with memory problems using positron emission tomography (PET) scans, making the company the first to bring to market an FDA-approved method that can directly detect this hallmark pathology of Alzheimer's disease.
Marcus E. Raichle is an American neurologist at the Washington University School of Medicine in Saint Louis, Missouri. He is a professor in the Department of Radiology with joint appointments in Neurology, Neurobiology and Biomedical Engineering. His research over the past 40 years has focused on the nature of functional brain imaging signals arising from PET and fMRI and the application of these techniques to the study of the human brain in health and disease. He received the Kavli Prize in Neuroscience “for the discovery of specialized brain networks for memory and cognition", together with Brenda Milner and John O’Keefe in 2014.
Brain positron emission tomography is a form of positron emission tomography (PET) that is used to measure brain metabolism and the distribution of exogenous radiolabeled chemical agents throughout the brain. PET measures emissions from radioactively labeled metabolically active chemicals that have been injected into the bloodstream. The emission data from brain PET are computer-processed to produce multi-dimensional images of the distribution of the chemicals throughout the brain.
Florbetapir (18F), sold under the brand name Amyvid, is a PET scanning radiopharmaceutical compound containing the radionuclide fluorine-18 that was approved for use in the United States in 2012, as a diagnostic tool for Alzheimer's disease. Florbetapir, like Pittsburgh compound B (PiB), binds to beta-amyloid, however fluorine-18 has a half-life of 109.75 minutes, in contrast to PiB's radioactive half life of 20 minutes. The longer life allows the tracer to accumulate significantly more in the brains of people with AD, particularly in the regions known to be associated with beta-amyloid deposits.
Florbetaben, sold under the brand name Neuraceq, is a diagnostic radiotracer developed for routine clinical application to visualize β-amyloid plaques in the brain. It is a fluorine-18 (18F)-labeled stilbene derivative.
Chester Mathis is an American chemist who is currently the Distinguished Professor of Radiology at University of Pittsburgh and holds the UPMC Endowed Chair of PET Research.
Carbon-11 choline is the basis of medical imaging technologies. Because of its involvement in biologic processes, choline is related to diseases, leading to the development of medical imaging techniques to monitor its concentration. When radiolabeled with 11CH3, choline is a useful a tracer in PET imaging. Carbon-11 is radioactive with a half-life of 20.38 minutes. By monitoring the gamma radiation resulting from the decay of carbon-11, the uptake, distribution, and retention of carbon-11 choline can be monitored.
Flortaucipir (18F), sold under the brand name Tauvid, is a radioactive diagnostic agent indicated for use with positron emission tomography (PET) imaging to image the brain.
Hartmuth Christian Kolb is a German chemist. He is considered one of the founders of click chemistry.