Evidence map›Paper›PMID 35680502›Full record

ArticleNuclear medicine and biology

Radiosynthesis and initial preclinical evaluation of [

Isaac M Jackson, Pablo J Buccino, E Carmen Azevedo, Mackenzie L Carlson, Audrey S Z Luo, Emily M Deal, Mausam Kalita, Samantha T Reyes, Xia Shao, Corinne Beinat and 7 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nuclear medicine and biology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Recent advances in [Nuclear medicine and biology · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 1 country.

Isaac M JacksonDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
Pablo J BuccinoDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
E Carmen AzevedoDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
Mackenzie L CarlsonDepartment of Bioengineering, Stanford University, Stanford, CA, United States of America.
Audrey S Z LuoDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
Emily M DealDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
Mausam KalitaDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
Samantha T ReyesDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
Xia ShaoMedicinal Chemistry Knowledge Center, Stanford ChEM-H, Stanford University, CA.
Corinne BeinatDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
Sydney C NagyDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
Aisling M ChaneyDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
David A AndersDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
Peter J H ScottDepartment of Radiology, University of Michigan, Ann Arbor, MI, United States of America.
Mark SmithMedicinal Chemistry Knowledge Center, Stanford ChEM-H, Stanford University, CA.
Bin ShenDepartment of Radiology, Stanford University, Stanford, CA, United States of America.
Michelle L JamesDepartment of Radiology, Stanford University, Stanford, CA, United States of America; Department of Neurology & Neurological Science, Stanford University, Stanford, CA, United States of America. Electronic address: mljames@stanford.edu.
Stanford University · USUniversity of Michigan–Ann Arbor · US

Funding

Development of a Novel PET Tracer for Imaging Microglial Function in Alzheimer's DiseaseF30AG074633 · NIA · STANFORD UNIVERSITY · PI JACKSON, ISAAC MACKENZIE · 2022 to 2023
$80k
NIA NIH HHS F30 AG074633
6 · The paper itself

Abstract

introChronic neuroinflammation and microglial dysfunction are key features of many neurological diseases, including Alzheimer's Disease and multiple sclerosis. While there is unfortunately a dearth of highly selective molecular imaging biomarkers/probes for studying microglia in vivo, P2Y12R has emerged as an attractive candidate PET biomarker being explored for this purpose. Importantly, P2Y12R is selectively expressed on microglia in the CNS and undergoes dynamic changes in expression according to inflammatory context (e.g., toxic versus beneficial/healing states), thus having the potential to reveal functional information about microglia in living subjects. Herein, we identified a high affinity, small molecule P2Y12R antagonist (AZD1283) to radiolabel and assess as a candidate radiotracer through in vitro assays and in vivo positron emission tomography (PET) imaging of both wild-type and total knockout mice and a non-human primate.

methodsFirst, we evaluated the metabolic stability and passive permeability of non-radioactive AZD1283 in vitro. Next, we radiolabeled [

resultsWe determined the half-life of AZD1283 in mouse and human liver microsomes to be 37 and > 160 min, respectively, and predicted passive CNS uptake with a small amount of active efflux, using a Caco-2 assay. Our radiolabeling efforts afforded [

conclusionDespite our initial encouraging liver microsome and Caco-2 monolayer data, in addition to the observed high stability of [

Indexed as

Positron-Emission TomographyAnimalsBiomarkersCaco-2 CellsHumansMacaca mulattaMiceMice, KnockoutNiacinSulfonamidesBiomarkersethyl 6-(4-((benzylsulfonyl)carbamoyl)piperidin-1-yl)-5-cyano-2-isopropylnicotinateNiacinSulfonamidesCarbon-11CyanationMicrogliaNeuroinflammationP2Y12RPET

Identifiers

PMID35680502
PMCPMC10413622
OpenAlexW4280496857

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.