Evidence map›Paper›PMID 22411831›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Reactive polymer enables efficient in vivo bioorthogonal chemistry.

Neal K Devaraj, Greg M Thurber, Edmund J Keliher, Brett Marinelli, Ralph Weissleder

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed
11.2field-weighted citation impact, top 1% 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

97 citing papers in PubMed, 197 citations in OpenAlex.

  1. Article
  2. Development of a First-in-Class Click Chemistry-Based Cancer Therapeutic, from Preclinical Evaluation to a First-in-Human Dose Escalation Clinical Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
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  4. Review
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  13. Bioorthogonal Click of Colloidal Gold Nanoparticles to Antibodies In vivo.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022
    Article
  14. Review
  15. Article
  16. Development ofPharmaceuticals (Basel, Switzerland) · 2022
    Article
  17. Review
  18. Article
  19. Direct Cu-mediated aromaticChemical science · 2021
    Article
  20. Article

37 more citing papers are in PubMed but not listed here.

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

5 authors at 3 institutions in 1 country.

Neal K DevarajCenter for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
Greg M Thurber
Edmund J Keliher
Brett Marinelli
Ralph Weissleder
Center for Systems Biology · USHarvard University · USMassachusetts General Hospital · US

Funding

StatisticsP50CA086355 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2000 to 2015
$27.8M
Training Grant in Molecular Imaging Research (MGH/HMS)T32CA079443 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2000 to 2025
$10.1M
Novel Clickdyes for Biomedical SensingR01EB010011 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2010 to 2017
$3.1M
Fast in vivo CLICK chemistries for PET imagingK01EB010078 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DEVARAJ, NEAL KRISHNA · 2010 to 2014
$852k
Intravital microscopy imaging systemS10RR026360 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2010 to 2010
$500k
NCI NIH HHS P50 CA086355NCI NIH HHS P50CA86355NCI NIH HHS T32 CA079443NCI NIH HHS T32CA079443NCRR NIH HHS S10 RR026360NIBIB NIH HHS K01 EB010078NIBIB NIH HHS K01EB010078NIBIB NIH HHS R01 EB010011NIBIB NIH HHS R01EB010011
6 · The paper itself

Abstract

There has been intense interest in the development of selective bioorthogonal reactions or "click" chemistry that can proceed in live animals. Until now however, most reactions still require vast surpluses of reactants because of steep temporal and spatial concentration gradients. Using computational modeling and design of pharmacokinetically optimized reactants, we have developed a predictable method for efficient in vivo click reactions. Specifically, we show that polymer modified tetrazines (PMT) are a key enabler for in vivo bioorthogonal chemistry based on the very fast and catalyst-free [4 + 2] tetrazine/trans-cyclooctene cycloaddition. Using fluorescent PMT for cellular resolution and (18)F labeled PMT for whole animal imaging, we show that cancer cell epitopes can be easily reacted in vivo. This generic strategy should help guide the design of future chemistries and find widespread use for different in vivo bioorthogonal applications, particularly in the biomedical sciences.

Indexed as

AnimalsBiocompatible MaterialsCell Line, TumorClick ChemistryEpitopesKineticsMiceMicroscopy, FluorescencePolymersPositron-Emission TomographyPyridinesTomography, X-Ray ComputedXenograft Model Antitumor AssaysBiocompatible MaterialsEpitopesPolymersPyridines

Identifiers

PMID22411831
PMCPMC3324005
OpenAlexW1980040652

What OpenQuestion holds

Textmetadata
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.