Article
Biochemistry & Molecular Biology
Nakul R. Raval, Gustavo Angarita, David Matuskey, Rachel Miller, Lindsey R. Drake, Michael Kapinos, Nabeel Nabulsi, Yiyun Huang, Richard E. Carson, Stephanie S. O'Malley, Kelly P. Cosgrove, Ansel T. Hillmer
Summary: The negative effects of alcohol on the immune system in both the periphery and the brain are not fully understood. This study used positron emission tomography to measure the immune response to alcohol in the brain, and found that alcohol significantly increased immune markers in the brain and affected plasma cytokines.
MOLECULAR PSYCHIATRY
(2023)
Article
Clinical Neurology
Wasim Khan, Louise A. Corben, Hiba Bilal, Lucy Vivash, Martin B. Delatycki, Gary F. Egan, Ian H. Harding
Summary: Neuroinflammation is significantly increased in certain brain regions of individuals with FRDA, and is related to the severity, duration, and age of onset of the disease. These findings suggest that neuroimmune activity may play a role in the pathogenesis and progression of FRDA.
MOVEMENT DISORDERS
(2022)
Article
Pharmacology & Pharmacy
Aline Morais de Souza, Caroline Cristiano Real, Mara de Souza Junqueira, Larissa Estessi de Souza, Fabio Luiz Navarro Marques, Carlos Alberto Buchpiguel, Roger Chammas, Marcelo Tatit Sapienza, Daniele de Paula Faria
Summary: This study evaluated the potential of PET imaging with [C-11](R)-PK11195 to assess breast tumor inflammation. The results showed that [C-11](R)-PK11195 was able to identify heterogeneous tumor inflammation in a murine model of breast cancer, and the uptake varied according to tumor size.
Article
Biochemistry & Molecular Biology
N. R. Zurcher, M. L. Loggia, J. E. Mullett, C. Tseng, A. Bhanot, L. Richey, B. G. Hightower, C. Wu, A. J. Parmar, R. I. Butterfield, J. M. Dubois, D. B. Chonde, D. Izquierdo-Garcia, H. Y. Wey, C. Catana, N. Hadjikhani, C. J. McDougle, J. M. Hooker
Summary: Lower regional TSPO expression in individuals with ASD compared to controls suggests abnormalities in neuroimmune processes or mitochondrial dysfunction. The stability and replicability of TSPO expression over time in ASD individuals were confirmed by voxelwise analysis.
MOLECULAR PSYCHIATRY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Tiago Reis Marques, Mattia Veronese, David R. Owen, Eugenii A. Rabiner, Graham E. Searle, Oliver D. Howes
Summary: In patients with schizophrenia, a substantial proportion of the [C-11]PBR28 signal represents specific binding to TSPO. After the administration of the TSPO ligand XBD173, there was a global reduction in [C-11]PBR28 uptake in all patients. The V-ND in schizophrenia patients was found to be similar to that in healthy controls, indicating that differences in non-specific binding do not explain discrepant PET findings in this disorder.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Review
Clinical Neurology
Peng-Fei Zhang, Fan Gao
Summary: Neuroinflammation may play a role in the progression of Parkinson's disease, as evidenced by elevated TSPO levels in various brain regions of PD patients compared to healthy controls. The involvement of neuroinflammation in PD pathogenesis remains ambiguous, with contrasting outcomes depending on the ligand used in the study.
JOURNAL OF NEUROLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Gjertrud L. Laurell, Pontus Plaven-Sigray, Aurelija Jucaite, Andrea Varrone, Kelly P. Cosgrove, Claus Svarer, Gitte M. Knudsen, R. Todd Ogden, Francesca Zanderigo, Simon Cervenka, Ansel T. Hillmer, Martin Schain
Summary: The study utilized a novel method SIME to estimate V-ND, demonstrating significantly lower V-ND in patients with alcohol use disorder and Parkinson's disease compared to controls. The findings suggest that differences in nondisplaceable binding may exist between different patient groups and conditions in TSPO PET studies.
JOURNAL OF NUCLEAR MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Renato Auriemma, Mattia Sponchioni, Umberto Capasso Palmiero, Giacomo Rossino, Arianna Rossetti, Andrea Marsala, Simona Collina, Alessandro Sacchetti, Davide Moscatelli, Marco Peviani
Summary: Reactive microgliosis is a prevalent pathological feature in various neurodegenerative diseases, and positron emission tomography (PET) using TSPO ligands like PBR28 has emerged as a valuable strategy to assess and monitor microgliosis. A synthetic pathway for a PBR28 derivative, PBR-alkyne, was explored to enable selective targeting of TSPO-expressing cells, demonstrating efficient internalization in cultured microglia-like cell lines when decorated on zwitterionic biodegradable polymer nanoparticles.
Review
Radiology, Nuclear Medicine & Medical Imaging
Catriona Wimberley, Sonia Lavisse, Ansel Hillmer, Rainer Hinz, Federico Turkheimer, Paolo Zanotti-Fregonara
Summary: This review focuses on the challenges associated with the quantification of TSPO PET images in the human brain, with a discussion of different methods and their advantages and drawbacks. Researchers are advised to understand the various quantification methods available and to choose the most appropriate one based on their research needs.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Review
Medicine, General & Internal
Ferdinando Corica, Maria Silvia De Feo, Joana Gorica, Marko Magdi Abdou Sidrak, Miriam Conte, Luca Filippi, Orazio Schillaci, Giuseppe De Vincentis, Viviana Frantellizzi
Summary: Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 2-3% of individuals over the age of 65. Neuroimaging techniques such as MRI, DAT-SPECT, and PET are used in the diagnosis of neurodegenerative disorders and focus on identifying morphological changes, nigrostriatal degeneration, and alterations in glucose metabolism in patients with parkinsonian syndromes. This study reviews the use of PET radiotracers targeting TSPO to assess neuroinflammation in PD and other neurodegenerative disorders.
Review
Radiology, Nuclear Medicine & Medical Imaging
Bastian Zinnhardt, Federico Roncaroli, Claudia Foray, Erjon Agushi, Bahiya Osrah, Gaelle Hugon, Andreas H. Jacobs, Alexandra Winkeler
Summary: Gliomas are common tumors of the central nervous system, with advances in genetic profiling and imaging technologies improving prognostic stratification and treatment decisions for patients. Amino acid PET and TSPO PET imaging have been widely used to study the heterogeneity and immune cell modulation of gliomas.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Cell Biology
Aisling M. Chaney, Haley C. Cropper, Poorva Jain, Edward Wilson, Federico Simonetta, Emily M. Johnson, Israt S. Alam, Ian T. J. Patterson, Michelle Swarovski, Marc Y. Stevens, Qian Wang, Carmen Azevedo, Sydney C. Nagy, Javier Ramos Benitez, Emily M. Deal, Hannes Vogel, Katrin I. Andreasson, Michelle L. James
Summary: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system, and imaging strategies using TREM1-PET have the potential to aid in the diagnosis and monitoring of therapeutic responses. In this study, the effectiveness of TREM1 PET imaging in the EAE mouse model of MS was validated, and it was found to be more sensitive than the established TSPO-PET imaging method. TREM1-PET imaging has the potential to play a role in the diagnosis of MS and monitoring of therapeutic responses to drug treatment.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Norbert Galldiks, Karl-Josef Langen, Nathalie L. Albert, Ian Law, Michelle M. Kim, Javier E. Villanueva-Meyer, Riccardo Soffietti, Patrick Y. Wen, Michael Weller, Joerg C. Tonn
Summary: Many studies on innovative PET tracers in brain tumor patients have been published recently, showing promising initial results. The Response Assessment in Neuro-Oncology (RANO) PET working group provides an overview of the literature on these novel investigational PET tracers and discusses new indications of established PET tracers. Based on preliminary findings, further evaluation of these novel investigational PET tracers is recommended due to their potential in tumor delineation and therapy monitoring.
Review
Radiology, Nuclear Medicine & Medical Imaging
Julia Schubert, Matteo Tonietto, Federico Turkheimer, Paolo Zanotti-Fregonara, Mattia Veronese
Summary: This technical note serves as a practical guide for implementing a supervised clustering algorithm (SVCA) reference region approach in the context of TSPO PET studies, highlighting its strengths and limitations in studying neuroinflammation. The SVCA method offers a non-invasive quantification of TSPO expression by identifying voxels with minimal specific binding in PET images, overcoming limitations of arterial sampling and TSPO contamination in anatomically-defined reference regions. The standardized implementation of SVCA methodology in TSPO PET analysis aims to improve replicability and comparability across study sites.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Review
Pharmacology & Pharmacy
Truong Giang Luu, Hee-Kwon Kim
Summary: TSPO plays important roles in cellular functions and its abnormal expression is associated with pathological disorders, making it a biomarker for related diseases. PET, as a non-invasive imaging technique, can detect diseases related to TSPO expression. Recent studies have focused on the development of F-18-labeled TSPO as PET tracers.
Article
Radiology, Nuclear Medicine & Medical Imaging
Eric E. Abrahamson, Jeffrey S. Stehouwer, Alberto L. Vazquez, Guo-Feng Huang, N. Scott Mason, Brian J. Lopresti, William E. Klunk, Chester A. Mathis, Milos D. Ikonomovic
Summary: A candidate CAA-selective compound was synthesized and showed affinity to A beta fibrils and lipophilicity, with selectivity for CAA versus parenchymal plaque deposits assessed. The compound demonstrated in-vivo preferential labeling of CM in living mice and displayed characteristics of Ali binding dyes in histological sections.
NUCLEAR MEDICINE AND BIOLOGY
(2021)
Article
Neuroimaging
Kevin J. Sullivan, Anran Liu, Chung-Chou H. Chang, Ann D. Cohen, Brian J. Lopresti, Davneet S. Minhas, Charles M. Laymon, William E. Klunk, Howard Aizenstein, Neelesh K. Nadkarni, David Loewenstein, M. Ilyas Kamboh, Mary Ganguli, Beth E. Snitz
Summary: A population-based perspective reveals that brain amyloid is common in community-dwelling older adults without dementia, and is associated with tau deposition. However, these pathologies show limited associations with concurrent cognitive performance.
BRAIN IMAGING AND BEHAVIOR
(2021)
Article
Biochemistry & Molecular Biology
Anton Lindberg, Ashley C. Knight, Daniel Sohn, Laszlo Rakos, Junchao Tong, April Radelet, N. Scott Mason, Jeffrey S. Stehouwer, Brian J. Lopresti, William E. Klunk, Johan Sandell, Alexander Sandberg, Per Hammarstrom, Samuel Svensson, Chester A. Mathis, Neil Vasdev
Summary: CBD-2115, a first-in-class 4R-tau radiotracer, showed high binding affinity and reliable synthesis, holding potential for further research on 4R-tauopathies.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Victor L. Villemagne, Brian J. Lopresti, Vincent Dore, Dana Tudorascu, Milos D. Ikonomovic, Samantha Burnham, Davneet Minhas, Tharick A. Pascoal, N. Scott Mason, Beth Snitz, Howard Aizenstein, Chester A. Mathis, Oscar Lopez, Christopher C. Rowe, William E. Klunk, Ann D. Cohen
Summary: This review examines the evidence and alternatives for establishing tau positivity with multiple tau-imaging tracers in the context of the amyloid, tau, and neurodegeneration framework, aiming to reach a consensus on normal and abnormal tau imaging values that can be universally implemented in clinical research and therapeutic trials.
JOURNAL OF NUCLEAR MEDICINE
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Alexandra Gogola, Davneet S. Minhas, Victor L. Villemagne, Ann D. Cohen, James M. Mountz, Tharick A. Pascoal, Charles M. Laymon, N. Scott Mason, Milos D. Ikonomovic, Chester A. Mathis, Beth E. Snitz, Oscar L. Lopez, William E. Klunk, Brian J. Lopresti
Summary: This study compared the characteristics of two frequently used tau PET tracers, F-18-flortaucipir and F-18-MK-6240, in the same subjects. The results showed that both tracers performed equally well in visual interpretations and were capable of quantifying signal in a common set of brain regions that develop tau pathology in Alzheimer disease. However, they also showed distinct patterns of apparent off-target binding, and F-18-MK-6240 exhibited a greater dynamic range in SUVR estimates.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Victor L. Villemagne, Ryuichi Harada, Vincent Dore, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Samantha Burnham, Natasha Krishnadas, Svetlana Bozinovski, Kun Huang, Brian J. Lopresti, Kazuhiko Yanai, Christopher C. Rowe, Nobuyuki Okamura
Summary: The study found that 18F-SMBT-1 is a highly selective and low nonspecific binding MAO-B tracer, which can potentially be used as a surrogate marker of reactive astrogliosis.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Neurosciences
Savannah Tollefson, Michael L. Himes, Katelyn M. Kozinski, Brian J. Lopresti, N. Scott Mason, Joseph Hibbeln, Matthew F. Muldoon, Rajesh Narendran
Summary: This study aimed to investigate the effects of DHA on TSPO binding, as well as cognitive performance and stress resilience. The results showed that individuals with low DHA had lower TSPO binding, contrary to our hypothesis. These findings also highlight the importance of considering lipid parameters when interpreting TSPO positron emission tomography clinical findings.
BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING
(2022)
Review
Biochemistry & Molecular Biology
Brian J. Lopresti, Sarah K. Royse, Chester A. Mathis, Savannah A. Tollefson, Rajesh Narendran
Summary: With the emergence of PET, psychiatry gained access to a non-invasive tool for assessing human brain function. Early applications focused on measuring blood flow and metabolism, but specific probes for dopamine and serotonin receptors were later developed. However, the development of monoamine-enhancing drugs was not very successful, leading to a shift in drug development towards other targets. In recent years, PET imaging techniques have also been developed for studying non-monoamine targets.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Esther M. Blessing, Ankit Parekh, Rebecca A. Betensky, James Babb, Natalie Saba, Ludovic Debure, Andrew W. Varga, Indu Ayappa, David M. Rapoport, Tracy A. Butler, Mony J. de Leon, Thomas Wisniewski, Brian J. Lopresti, Ricardo S. Osorio
Summary: This study found that lower body temperature is associated with increased tau pathology in cognitively normal older adults, suggesting that temperature may play an important role in the development of Alzheimer's disease.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Sarah K. Royse, Brian J. Lopresti, Chester A. Mathis, Savannah Tollefson, Rajesh Narendran
Summary: Early PET applications in psychiatry aimed to identify cerebral blood flow and metabolism abnormalities, but the need for more specific neurochemical imaging probes became evident. The development of monoaminergic PET radiopharmaceuticals was driven by the belief in the centrality of monoamine dysfunction in psychiatric disorders. However, as drug development shifted away from monoamines, new PET imaging agents for non-monoamine targets were developed. Part two of the review focuses on clinical research studies using these novel targets and radiotracers across different psychiatric disorders.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Geriatrics & Gerontology
Minjie Wu, Noah Schweitzer, Bistra E. Iordanova, Edythe Halligan-Eddy, Dana L. Tudorascu, Chester A. Mathis, Brian J. Lopresti, M. Ilyas Kamboh, Ann D. Cohen, Beth E. Snitz, William E. Klunk, Howard J. Aizenstein
Summary: This study explored the interactive effects of small vessel disease (SVD) and amyloid-beta (Aβ) pathology on hippocampal functional connectivity and volume in cognitively normal older adults. The results showed that in older adults with white matter hyperintensities (WMH+), higher Aβ burden was associated with increased hippocampal local connectivity and lower gray matter density in the medial temporal lobe (MTL). In older adults without WMH, higher Aβ burden was associated with increased hippocampal distal connectivity and no changes in MTL gray matter density. These findings provide support for a hippocampal excitotoxicity model linking SVD to neurodegeneration and the progression to Alzheimer's disease (AD).
AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Bieneke Janssen, Guilong Tian, Zsofia Lengyel-Zhand, Chia-Ju Hsieh, Marshall G. Lougee, Aladdin Riad, Kuiying Xu, Catherine Hou, Chi-Chang Weng, Brian J. Lopresti, Hee Jong Kim, Vinayak V. Pagar, John J. Ferrie, Benjamin A. Garcia, Chester A. Mathis, Kelvin Luk, E. James Petersson, Robert H. Mach
Summary: In this study, a new radioligand with high affinity (<10 nM) for α-synuclein fibrils and PD tissue was identified through a similarity search. This study suggests that a simple in silico approach is a promising strategy to identify novel ligands for target proteins in the CNS and can be radiolabeled for PET neuroimaging studies.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Meeting Abstract
Endocrinology & Metabolism
Kristine Wilckens, Minjie Wu, Howard Aizenstein, Beth Snitz, Dana Tudorascu, Davneet Minhas, Brian Lopresti, Oscar Lopez, Charles Laymon, Victor Villemagne, Chester Mathis, William Klunk, Ann Cohen
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Meeting Abstract
Neurosciences
Linghai Wang, Howard Aizenstein, Brian Lopresti, Dana Tudorascu, Beth Snitz, William Klunk, Minjie Wu
BIOLOGICAL PSYCHIATRY
(2022)
Meeting Abstract
Endocrinology & Metabolism
Davneet Minhas, Anish Ghodadra, Zheming Yu, Sarah K. Royse, Howard Aizenstein, Ann Cohen, Dana Tudorascu, Brian Lopresti, Chester A. Mathis, William E. Klunk, Charles Laymon
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)