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Evaluation of integrin αvβ6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis.
Nat. Commun. 10:4673 (2019)
Verlagsversion
Forschungsdaten
DOI
PMC
Advances in precision molecular imaging promise to transform our ability
to detect, diagnose and treat disease. Here, we describe the
engineering and validation of a new cystine knot peptide (knottin) that
selectively recognizes human integrin αvβ6 with single-digit
nanomolar affinity. We solve its 3D structure by NMR and x-ray
crystallography and validate leads with 3 different radiolabels in
pre-clinical models of cancer. We evaluate the lead tracer’s safety,
biodistribution and pharmacokinetics in healthy human volunteers, and
show its ability to detect multiple cancers (pancreatic, cervical and
lung) in patients at two study locations. Additionally, we demonstrate
that the knottin PET tracers can also detect fibrotic lung disease in
idiopathic pulmonary fibrosis patients. Our results indicate that these
cystine knot PET tracers may have potential utility in multiple disease
states that are associated with upregulation of integrin αvβ6.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
11.878
2.805
31
41
Anmerkungen
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Alpha-v-integrins; Tgf-beta; Prognostic Biomarker; In-vivo; Expression; Pituitary; Peptide; Lung; Recognition; Target
Sprache
Veröffentlichungsjahr
2019
HGF-Berichtsjahr
2019
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Zeitschrift
Nature Communications
Quellenangaben
Band: 10,
Heft: 1,
Artikelnummer: 4673
Verlag
Nature Publishing Group
Verlagsort
London
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Computational Biology (ICB)
POF Topic(s)
30205 - Bioengineering and Digital Health
Forschungsfeld(er)
Enabling and Novel Technologies
PSP-Element(e)
G-503800-001
WOS ID
WOS:000489818900002
Scopus ID
85073182029
PubMed ID
31611594
Erfassungsdatum
2019-10-17