Evidence map›Paper›PMID 25418333›Full record

ArticleBioconjugate chemistry2014

Chemoenzymatic strategy for the synthesis of site-specifically labeled immunoconjugates for multimodal PET and optical imaging.

Brian M Zeglis, Charles B Davis, Dalya Abdel-Atti, Sean D Carlin, Aimei Chen, Robert Aggeler, Brian J Agnew, Jason S Lewis

Open access · greenAbstract read
In one paragraph

Article in Bioconjugate chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

45 citing papers in PubMed, 80 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. The Evaluation of (1Molecules (Basel, Switzerland) · 2025
    Article
  5. Review
  6. First-in-Human Evaluation of Site-Specifically LabeledJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024
    Article
  7. Site-SpecificBioconjugate chemistry · 2023
    Article
  8. Article
  9. Article
  10. Synthesis andBioconjugate chemistry · 2022
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Contemporary Approaches for Site-Selective Dual Functionalization of Proteins.Angewandte Chemie (International ed. in English) · 2021
    Review
  16. Review
  17. Review
  18. Polyazamacrocycle Ligands FacilitateInorganic chemistry · 2020
    Article
  19. Article
  20. Article
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

8 authors at 2 institutions in 1 country.

Brian M ZeglisDepartment of Radiology, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.
Charles B Davis
Dalya Abdel-Atti
Sean D Carlin
Aimei Chen
Robert Aggeler
Brian J Agnew
Jason S Lewis
Memorial Sloan Kettering Cancer Center · USThermo Fisher Scientific (United States) · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Memorial Sloan Kettering Small Animal Imaging ResearchR24CA083084 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI KOUTCHER, JASON ARTHUR · 1999 to 2006
$4.4M
Pretargeted Radioimmunotherapy Based on Bioorthogonal Click ChemistryK99CA178205 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ZEGLIS, BRIAN MATTHEW · 2014 to 2014
$108k
NCI NIH HHS 1K99CA178205-01A1NCI NIH HHS K99 CA178205NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA08748NCI NIH HHS R24 CA083084NCI NIH HHS R24 CA83084
6 · The paper itself

Abstract

The complementary nature of positron emission tomography (PET) and optical imaging (OI) has fueled increasing interest in the development of multimodal PET/OI probes that can be employed during the diagnosis, staging, and surgical treatment of cancer. Due to their high selectivity and affinity, antibodies have emerged as promising platforms for the development of hybrid PET/OI agents. However, the lack of specificity of many bioconjugation reactions can threaten immunoreactivity and lead to poorly defined constructs. To circumvent this issue, we have developed a chemoenzymatic strategy for the construction of multimodal PET/OI immunoconjugates that have been site-specifically labeled on the heavy chain glycans. The methodology consists of four steps: (1) the enzymatic removal of the terminal galactose residues on the heavy chain glycans; (2) the enzymatic incorporation of azide-bearing galactose (GalNAz) residues into the heavy chain glycans; (3) the strain-promoted click conjugation of chelator- and fluorophore-modified dibenzocyclooctynes to the azide-modified sugars; and (4) the radiolabeling of the immunoconjugate. For proof-of-concept, a model system was created using the colorectal cancer-targeting antibody huA33, the chelator desferrioxamine (DFO), the positron-emitting radiometal (89)Zr, and the near-infrared fluorescent dye Alexa Fluor 680. The bioconjugation strategy is robust and reproducible, reliably producing well-defined and immunoreactive conjugates labeled with (89)Zr, Alexa Fluor 680, or an easily and precisely tuned mixture of the two reporters. In in vivo PET and fluorescence imaging experiments, a hybrid (89)Zr- and Alexa Fluor 680-labeled huA33 conjugate displayed high levels of specific uptake (>45% ID/g) in athymic nude mice bearing A33 antigen-expressing SW1222 colorectal cancer xenografts.

Indexed as

AnimalsColorectal NeoplasmsElectrophoresis, Polyacrylamide GelFluorescent DyesGalactoseHumansImmunoconjugatesMiceMultimodal ImagingNeoplasms, ExperimentalOptical ImagingPolysaccharidesPositron-Emission TomographyRadioisotopesTissue DistributionXenograft Model Antitumor AssaysFluorescent DyesGalactoseImmunoconjugatesPolysaccharidesRadioisotopesZirconium

Identifiers

PMID25418333
PMCPMC4334285
OpenAlexW2086114352

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.