PuSH - Publikationsserver des Helmholtz Zentrums München

Kimura, R.H.* ; Wang, L.* ; Shen, B.* ; Huo, L.* ; Tummers, W.* ; Filipp, F.V. ; Guo, H.H.* ; Haywood, T.* ; Abou-Elkacem, L.* ; Baratto, L.* ; Habte, F.* ; Devulapally, R.* ; Witney, T.H.* ; Cheng, Y.* ; Tikole, S. ; Chakraborti, S.* ; Nix, J.* ; Bonagura, C.A.* ; Hatami, N.* ; Mooney, J.J.* ; Desai, T.* ; Turner, S.* ; Gaster, R.S.* ; Otte, A.* ; Visser, B.C.* ; Poultsides, G.A.* ; Norton, J.* ; Park, W.* ; Stolowitz, M.* ; Lau, K.* ; Yang, E.* ; Natarajan, A.* ; Ilovich, O.* ; Srinivas, S.* ; Srinivasan, A.* ; Paulmurugan, R.* ; Willmann, J.* ; Chin, F.T.* ; Cheng, Z.* ; Iagaru, A.* ; Li, F.* ; Gambhir, S.S.*

Evaluation of integrin αvβ6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis.

Nat. Commun. 10:4673 (2019)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Alpha-v-integrins; Tgf-beta; Prognostic Biomarker; In-vivo; Expression; Pituitary; Peptide; Lung; Recognition; Target
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 10, Heft: 1, Seiten: , Artikelnummer: 4673 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)