About

Shuangping Li is an assistant professor of Statistics and Data Science at Yale University. He completed his Ph.D. in Applied and Computational Mathematics at Princeton University in May 2022 under the supervision of Professor Allan Sly and Professor Emmanuel Abbe. Prior to his doctoral studies, he earned a B.Sc. in Mathematics from the University of Hong Kong. Before joining Yale, he was a Stein Fellow in the Department of Statistics at Stanford University from 2022 to 2025. His research interests encompass probability theory, high-dimensional statistics, theoretical machine learning, and the theory of algorithms. Throughout his career, he has been actively involved in delivering talks at numerous prestigious institutions and conferences, reflecting his engagement with the academic community in his fields of expertise.

Research topics

• Biochemistry
• Medicine
• Immunology
• Pathology
• Biology
• Internal medicine
• Chemistry
• Nuclear magnetic resonance
• Physics
• Cell biology
• Nuclear medicine
• Neuroscience

Selected publications

• Effects of Long-Term Cocaine Self-Administration on Kappa Opioid Receptors in Socially Housed Cynomolgus Monkeys as Assessed With Positron Emission Tomography Imaging and Neuronally Derived Exosomes

  Biological Psychiatry · 2025-03-05 · 4 citations

  articleOpen access
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• PET Imaging of Kappa Opioid Receptors in Socially Housed Female and Male Monkeys: Effects of Chronic Cocaine Self-Administration

  Drug and Alcohol Dependence · 2024-07-01

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• Noninvasive quantification of [18F]SynVesT-1 binding using simplified reference tissue model 2

  European Journal of Nuclear Medicine and Molecular Imaging · 2024-08-19 · 9 citations

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• Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at ¹⁸F-SynVesT-1 Brain PET Imaging

  Radiology · 2024-11-01 · 16 citations

  articleOpen access

  Plasma phosphorylated tau 181 (p-tau-181) and glial fibrillary acidic protein (GFAP) have potential predictive value for identifying synaptic density as measured using 18 F-SynVesT-1 brain PET; the relationship of plasma p-tau-181 and GFAP with synapse loss might be influenced by tau aggregation rather than amyloid-β deposition or cortical thickness.

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• First-in-Human Study of¹⁸F-SynVesT-2: An SV2A PET Imaging Probe with Fast Brain Kinetics and High Specific Binding

  Journal of Nuclear Medicine · 2024-02-15 · 14 citations

  articleOpen access

  PET imaging of synaptic vesicle glycoprotein 2A allows for noninvasive quantification of synapses. This first-in-human study aimed to evaluate the kinetics, test–retest reproducibility, and extent of specific binding of a recently developed synaptic vesicle glycoprotein 2A PET ligand, (<i>R</i>)-4-(3-(¹⁸F-fluoro)phenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidine-2-one (¹⁸F-SynVesT-2), with fast brain kinetics. <b>Methods:</b> Nine healthy volunteers participated in this study and were scanned on a High Resolution Research Tomograph scanner with ¹⁸F-SynVesT-2. Five volunteers were scanned twice on 2 different days. Five volunteers were rescanned with preinjected levetiracetam (20 mg/kg, intravenously). Arterial blood was collected to calculate the plasma free fraction and generate the arterial input function. Individual MR images were coregistered to a brain atlas to define regions of interest for generating time–activity curves, which were fitted with 1- and 2-tissue-compartment (1TC and 2TC) models to derive the regional distribution volume (<i>V</i>_T). The regional nondisplaceable binding potential (<i>BP</i>_ND) was calculated from 1TC <i>V</i>_T, using the centrum semiovale (CS) as the reference region. <b>Results:</b>¹⁸F-SynVesT-2 was synthesized with high molar activity (187 ± 69 MBq/nmol, <i>n</i> = 19). The parent fraction of ¹⁸F-SynVesT-2 in plasma was 28% ± 8% at 30 min after injection, and the plasma free fraction was high (0.29 ± 0.04). ¹⁸F-SynVesT-2 entered the brain quickly, with an SUV_peak of 8 within 10 min after injection. Regional time–activity curves fitted well with both the 1TC and the 2TC models; however, <i>V</i>_T was estimated more reliably using the 1TC model. The 1TC <i>V</i>_T ranged from 1.9 ± 0.2 mL/cm³ in CS to 7.6 ± 0.8 mL/cm³ in the putamen, with low absolute test–retest variability (6.0% ± 3.6%). Regional <i>BP</i>_ND ranged from 1.76 ± 0.21 in the hippocampus to 3.06 ± 0.29 in the putamen. A 20-min scan was sufficient to provide reliable <i>V</i>_T and <i>BP</i>_ND. <b>Conclusion:</b>¹⁸F-SynVesT-2 has fast kinetics, high specific uptake, and low nonspecific uptake in the brain. Consistent with the nonhuman primate results, the kinetics of ¹⁸F-SynVesT-2 is faster than the kinetics of ¹¹C-UCB-J and ¹⁸F-SynVesT-1 in the human brain and enables a shorter dynamic scan to derive physiologic information on cerebral blood flow and synapse density.

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• Imaging a putative marker of brain cortisol regulation in alcohol use disorder

  Neurobiology of Stress · 2024-01-21 · 5 citations

  articleOpen access

  Stress is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis, initiating the release of glucocorticoid hormones, such as cortisol. Alcohol consumption can lead to HPA axis dysfunction, including altered cortisol levels. Until recently, research has only been able to examine peripheral cortisol associated with alcohol use disorder (AUD) in humans. We used positron emission tomography (PET) brain imaging with the radiotracer [18F]AS2471907 to measure 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a cortisol-regenerating enzyme, in people with AUD compared to healthy controls. We imaged 9 individuals with moderate to severe AUD (5 men, 4 women; mean age = 38 years) and 12 healthy controls (8 men, 4 women; mean age = 29 years). Participants received 93.5 ± 15.6 MBq of the 11β-HSD1 inhibitor radiotracer [18F]AS2471907 as a bolus injection and were imaged for 150–180 min on the High-Resolution Research Tomograph. 11β-HSD1 availability was quantified by [18F]AS2471907 volume of distribution (VT; mL/cm3). A priori regions of interest included amygdala, anterior cingulate cortex (ACC), hippocampus, ventromedial PFC (vmPFC) and caudate. Individuals with AUD consumed 52.4 drinks/week with 5.8 drinking days/week. Healthy controls consumed 2.8 drinks/week with 1.3 drinking days/week. Preliminary findings suggest that [18F]AS2471907 VT was higher in amygdala, ACC, hippocampus, vmPFC, and caudate of those with AUD compared to healthy controls (p < 0.05). In AUD, vmPFC [18F]AS2471907 VT was associated with drinks per week (r = 0.81, p = 0.01) and quantity per drinking episode (r = 0.75, p = 0.02). This is the first in vivo examination of 11β-HSD1 availability in individuals with AUD. Our data suggest higher brain availability of the cortisol-regenerating enzyme 11β-HSD1 in people with AUD (vs. controls), and that higher vmPFC 11β-HSD1 availability is related to greater alcohol consumption. Thus, in addition to the literature suggesting that people with AUD have elevated peripheral cortisol, our findings suggest there may also be heightened central HPA activity. These findings set the foundation for future hypotheses on mechanisms related to HPA axis function in this population.

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• Discovery of 4‐(isopentyloxy)‐3‐nitrobenzamide derivatives as xanthine oxidase inhibitors through a non‐anthraquinone exploration

  Archiv der Pharmazie · 2024-07-04 · 2 citations

  articleOpen access

  Abstract In our previous study, we reported a series of N ‐(9,10‐anthraquinone‐2‐carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug‐like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure–activity relationship (SAR) studies, we identified a series of 4‐(isopentyloxy)‐3‐nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4‐isopentyloxy‐ N ‐(1 H ‐pyrazol‐3‐yl)‐3‐nitrobenzamide ( 6k ), demonstrated exceptional in vitro potency with an IC 50 value of 0.13 μM. Compound 6k showed favorable drug‐like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d , 6k exhibited a substantial 24‐fold improvement in IC 50 , along with a 1.6‐fold enhancement in LE and a 3.7‐fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug‐like characteristics, thereby warranting further exploration.

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• Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment

  Alzheimer s & Dementia · 2024-04-18 · 24 citations

  articleOpen access

  INTRODUCTION: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD). METHODS: F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition. RESULTS: CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition. CONCLUSIONS: Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked. HIGHLIGHTS: Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition. With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD.

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• The associations between synaptic density and “A/T/N” biomarkers in Alzheimer’s disease: An ¹⁸ F-SynVesT-1 PET/MR study

  Journal of Cerebral Blood Flow & Metabolism · 2024-01-31 · 18 citations

  articleOpen access

  A newly developed SV2A radiotracer, 18 F-SynVesT-1, was used in this study to investigate synaptic density and its association with Alzheimer’s disease (AD) “A/T/N” biomarkers. The study included a cohort of 97 subjects, consisting of 64 patients with cognitive impairment (CI) and 33 individuals with normal cognition (CU). All subjects underwent 18 F-SynVesT-1 PET/MR and 18 F-florbetapir PET/CT scans. Additionally, a subgroup of individuals also underwent 18 F-MK-6240, 18 F-FDG PET/CT, plasma Aβ42/Aβ40 and p-tau181 tests. The differences in synaptic density between the groups and the correlations between synaptic density and AD “A/T/N” biomarkers were analyzed. The results showed that compared to the CU group, the CI with Aβ+ (CI+) group exhibited the most pronounced synapse loss in the hippocampus, with some loss also observed in the neocortex. Furthermore, synaptic density in the hippocampus and parahippocampal gyrus showed associations with AD biomarkers detected by both imaging and plasma tests in the CI group. The associations between synaptic density and FDG uptake and hippocampal volume were also observed in the CI+ group. In conclusion, the study demonstrated significant synaptic density loss, as measured by the promising tracer 18 F-SynVesT-1, and its close correlation with “A/T/N” biomarkers in patients with both Alzheimer’s clinical syndrome and pathological changes.

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• Quantification of Multi-Organ 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme Levels in a Zucker Fatty Rat Model: A PET Imaging Study

  Molecular Imaging · 2024-01-01 · 1 citations

  articleOpen access

  Background In rodents, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyzes the conversion of inactive 11-dehydrocorticosterone to the active hormone corticosterone. Dysregulation of intracellular glucocorticoid action is implicated in metabolic diseases. Assessing 11β-HSD1 enzyme levels in vivo may be key to understanding obesity pathophysiology. Objective We used a Zucker Fatty (ZF) rat model and [ 18 F]AS2471907 PET imaging to determine appropriate kinetic modeling methods and assess changes in 11β-HSD1 levels due to obesity in the liver, white and brown adipose tissue (WAT/BAT), and brain. Material and Methods To validate [ 18 F]AS2471907 PET in preclinical models, time-activity curves (TACs) were generated and kinetic modeling was performed with image-derived input functions (IDIFs) extracted from multiple locations. Quantitative estimates of radioligand binding were compared with ex vivo 11β-HSD1 protein expression. Validated quantitative PET kinetic modeling methods were then used to assess differences in 11β-HSD1 between lean and obese ZF rats. Metabolic disease status was confirmed with stable isotopes tracer studies of glucose and fatty acid metabolism. Results Obesity is associated with decreased brain 11β-HSD1 levels, measured by [ 18 F]AS2471907 PET, which correlated with measures of glucose and fatty acid metabolism. Conclusion We demonstrate that [ 18 F]AS2471907 PET can provide useful quantification of 11β-HSD1 levels in a rodent model of obesity.

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Frequent coauthors

• Yiyun Huang

  Yale University

  127 shared

• Richard E. Carson

  70 shared

• Jim Ropchan

  Yale University

  57 shared

• Zhengxin Cai

  Anhui University of Technology

  51 shared

• Nabeel Nabulsi

  Yale University

  50 shared

• David Labaree

  Yale Cancer Center

  40 shared

• Fang Xie

  Fudan University

  40 shared

• Qi Huang

  Fudan University

  40 shared

Labs

• Shuangping Li LabPI