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Development of Novel CNS PET Radiotracers for Shedding Light on Neuroinflammation
Development of Novel CNS PET Radiotracers for Shedding Light on Neuroinflammation
Development of Novel CNS PET Radiotracers for Shedding Light on Neuroinflammation

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202104847
ISBN  
9798288816512
DDC  
571.6
저자명  
Jackson, Isaac Mackenzie.
서명/저자  
Development of Novel CNS PET Radiotracers for Shedding Light on Neuroinflammation
발행사항  
[Sl] : Stanford University, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
130 p
주기사항  
Source: Dissertations Abstracts International, Volume: 87-02, Section: B.
주기사항  
Advisor: James, Michelle.
학위논문주기  
Thesis (Ph.D.)--Stanford University, 2025.
초록/해제  
요약Neuroinflammation plays a key role in the pathogenesis and progression of many neurological conditions including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Innate immune responses involving microglia -- resident cells of the central nervous system (CNS) that act in concert with peripheral myeloid cells such as macrophages and neutrophils -- have been implicated as major drivers of neuroinflammation and are among the first cellular events to occur in the context of CNS injury or infection. Accordingly, many ongoing efforts are focused on targeting the innate immune system to better understand and treat neurological diseases. Positron emission tomography (PET) is a powerful molecular imaging technique with the ability to non-invasively monitor biochemical and cellular processes including innate immune function in vivo. Unfortunately, currently available PET approaches and radiotracers for imaging innate immune function possess significant limitations. Furthermore, development of new CNS radiotracers is arduous and resource intensive, with limited computational tools available to facilitate efficient molecule design/prioritization. To address these challenges, I have developed and evaluated two carbon-11 labeled small molecule PET tracer candidates for two highly promising biomarkers of innate immune function and translated a fluorine-18 labeled dendrimer-based PET tracer for clinical imaging of reactive microglia and macrophages. In parallel, I have developed a new computational approach to improve CNS tracer design and shown that it has a high positive predictive value for differentiating successful and non-CNS penetrant small molecule PET radiotracers prior to in vivo imaging studies. Cumulatively, these new radiotracers and computational methods have the potential to shed light on neuroinflammation in a range of neurological diseases and facilitate efficient future development of next-generation CNS-penetrant radiotracers.
일반주제명  
Cells
일반주제명  
Alzheimer's disease
일반주제명  
Liver
일반주제명  
Disease
일반주제명  
Chronic illnesses
일반주제명  
Nonsteroidal anti-inflammatory drugs
일반주제명  
Amyotrophic lateral sclerosis
일반주제명  
Biomarkers
일반주제명  
Blood platelets
일반주제명  
Nervous system
일반주제명  
Metabolism
일반주제명  
Inflammation
일반주제명  
Tissues
일반주제명  
Pathogenesis
일반주제명  
Ischemia
일반주제명  
Benzodiazepines
일반주제명  
Polymorphism
일반주제명  
Parkinson's disease
일반주제명  
Traumatic brain injury
일반주제명  
Chemistry
일반주제명  
Neurosciences
일반주제명  
Medical imaging
키워드  
Central nervous system
키워드  
Positron emission tomography
키워드  
Neuroinflammation
기타저자  
Stanford University.
기본자료저록  
Dissertations Abstracts International. 87-02B.
전자적 위치 및 접속  
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MARC

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■0820  ▼a571.6
■1001  ▼aJackson,  Isaac  Mackenzie.
■24510▼aDevelopment  of  Novel  CNS  PET  Radiotracers  for  Shedding  Light  on  Neuroinflammation
■260    ▼a[Sl]▼bStanford  University▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a130  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  87-02,  Section:  B.
■500    ▼aAdvisor:  James,  Michelle.
■5021  ▼aThesis  (Ph.D.)--Stanford  University,  2025.
■520    ▼aNeuroinflammation  plays  a  key  role  in  the  pathogenesis  and  progression  of  many  neurological  conditions  including  stroke,  Alzheimer's  disease,  amyotrophic  lateral  sclerosis,  and  multiple  sclerosis.  Innate  immune  responses  involving  microglia  --  resident  cells  of  the  central  nervous  system  (CNS)  that  act  in  concert  with  peripheral  myeloid  cells  such  as  macrophages  and  neutrophils  --  have  been  implicated  as  major  drivers  of  neuroinflammation  and  are  among  the  first  cellular  events  to  occur  in  the  context  of  CNS  injury  or  infection.  Accordingly,  many  ongoing  efforts  are  focused  on  targeting  the  innate  immune  system  to  better  understand  and  treat  neurological  diseases.  Positron  emission  tomography  (PET)  is  a  powerful  molecular  imaging  technique  with  the  ability  to  non-invasively  monitor  biochemical  and  cellular  processes  including  innate  immune  function  in  vivo.  Unfortunately,  currently  available  PET  approaches  and  radiotracers  for  imaging  innate  immune  function  possess  significant  limitations.  Furthermore,  development  of  new  CNS  radiotracers  is  arduous  and  resource  intensive,  with  limited  computational  tools  available  to  facilitate  efficient  molecule  design/prioritization.  To  address  these  challenges,  I  have  developed  and  evaluated  two  carbon-11  labeled  small  molecule  PET  tracer  candidates  for  two  highly  promising  biomarkers  of  innate  immune  function  and  translated  a  fluorine-18  labeled  dendrimer-based  PET  tracer  for  clinical  imaging  of  reactive  microglia  and  macrophages.  In  parallel,  I  have  developed  a  new  computational  approach  to  improve  CNS  tracer  design  and  shown  that  it  has  a  high  positive  predictive  value  for  differentiating  successful  and  non-CNS  penetrant  small  molecule  PET  radiotracers  prior  to  in  vivo  imaging  studies.  Cumulatively,  these  new  radiotracers  and  computational  methods  have  the  potential  to  shed  light  on  neuroinflammation  in  a  range  of  neurological  diseases  and  facilitate  efficient  future  development  of  next-generation  CNS-penetrant  radiotracers.
■590    ▼aSchool  code:  0212.
■650  4▼aCells
■650  4▼aAlzheimer's  disease
■650  4▼aLiver
■650  4▼aDisease
■650  4▼aChronic  illnesses
■650  4▼aNonsteroidal  anti-inflammatory  drugs
■650  4▼aAmyotrophic  lateral  sclerosis
■650  4▼aBiomarkers
■650  4▼aBlood  platelets
■650  4▼aNervous  system
■650  4▼aMetabolism
■650  4▼aInflammation
■650  4▼aTissues
■650  4▼aPathogenesis
■650  4▼aIschemia
■650  4▼aBenzodiazepines
■650  4▼aPolymorphism
■650  4▼aParkinson's  disease
■650  4▼aTraumatic  brain  injury
■650  4▼aChemistry
■650  4▼aNeurosciences
■650  4▼aMedical  imaging
■653    ▼aCentral  nervous  system
■653    ▼aPositron  emission  tomography
■653    ▼aNeuroinflammation
■690    ▼a0485
■690    ▼a0574
■690    ▼a0317
■71020▼aStanford  University.
■7730  ▼tDissertations  Abstracts  International▼g87-02B.
■790    ▼a0212
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359194▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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