Evidence map›Paper›PMID 22461363›Full record

ArticleCirculation research2012

Nanobodies targeting mouse/human VCAM1 for the nuclear imaging of atherosclerotic lesions.

Alexis Broisat, Sophie Hernot, Jakub Toczek, Jens De Vos, Laurent M Riou, Sandrine Martin, Mitra Ahmadi, Nicole Thielens, Ulrich Wernery, Vicky Caveliers and 5 more

Open access · bronzeAbstract readEvaluation Study
In one paragraph

Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
13.0field-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

99 citing papers in PubMed, 195 citations in OpenAlex.

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  8. Optimizing the Therapeutic Index of sdAb-Based Radiopharmaceuticals Using Pretargeting.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024
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  17. PET/MR imaging of inflammation in atherosclerosis.Nature biomedical engineering · 2023
    Review
  18. Article
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  20. Single-Domain Antibody Theranostics on the Horizon.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 3 countries.

Alexis BroisatLaboratoire des Radiopharmaceutiques Bioclinique, INSERM 1039, Grenoble, France. alexis.broisat@inserm.fr
Sophie Hernot
Jakub Toczek
Jens De Vos
Laurent M Riou
Sandrine Martin
Mitra Ahmadi
Nicole Thielens
Ulrich Wernery
Vicky Caveliers
Serge Muyldermans
Tony Lahoutte
Daniel Fagret
Catherine Ghezzi
Nick Devoogdt
Vlaams Instituut voor Biotechnologie · BEInserm · FRCentral Veterinary Research Laboratory · AEVrije Universiteit Brussel · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleA noninvasive tool allowing the detection of vulnerable atherosclerotic plaques is highly needed. By combining nanomolar affinities and fast blood clearance, nanobodies represent potential radiotracers for cardiovascular molecular imaging. Vascular cell adhesion molecule-1 (VCAM1) constitutes a relevant target for molecular imaging of atherosclerotic lesions.

objectiveWe aimed to generate, radiolabel, and evaluate anti-VCAM1 nanobodies for noninvasive detection of atherosclerotic lesions. METHODS AND

resultsTen anti-VCAM1 nanobodies were generated, radiolabeled with technetium-99m, and screened in vitro on mouse and human recombinant VCAM1 proteins and endothelial cells and in vivo in apolipoprotein E-deficient (ApoE(-/-)) mice. A nontargeting control nanobody was used in all experiments to demonstrate specificity. All nanobodies displayed nanomolar affinities for murine VCAM1. Flow cytometry analyses using human human umbilical vein endothelial cells indicated murine and human VCAM1 cross-reactivity for 6 of 10 nanobodies. The lead compound cAbVCAM1-5 was cross-reactive for human VCAM1 and exhibited high lesion-to-control (4.95±0.85), lesion-to-heart (8.30±1.11), and lesion-to-blood ratios (4.32±0.48) (P<0.05 versus control C57Bl/6J mice). Aortic arch atherosclerotic lesions of ApoE(-/-) mice were successfully identified by single-photon emission computed tomography imaging. (99m)Tc-cAbVCAM1-5 binding specificity was demonstrated by in vivo competition experiments. Autoradiography and immunohistochemistry further confirmed cAbVCAM1-5 uptake in VCAM1-positive lesions.

conclusionsThe (99m)Tc-labeled, anti-VCAM1 nanobody cAbVCAM1-5 allowed noninvasive detection of VCAM1 expression and displayed mouse and human cross-reactivity. Therefore, this study demonstrates the potential of nanobodies as a new class of radiotracers for cardiovascular applications. The nanobody technology might evolve into an important research tool for targeted imaging of atherosclerotic lesions and has the potential for fast clinical translation.

Indexed as

Radioactive TracersAnimalsApolipoproteins EAtherosclerosisBiomarkersCell LineDisease Models, AnimalEndothelium, VascularFemaleHumansIn Vitro TechniquesMiceMice, KnockoutMolecular ImagingRadioimmunodetectionRadiopharmaceuticalsApolipoproteins EBiomarkersRadioactive TracersRadiopharmaceuticalsTechnetiumVascular Cell Adhesion Molecule-1

Identifiers

PMID22461363
PMCPMC3918224
OpenAlexW2158621028

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.