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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)
Publ. Version/Full Text Research data 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Alpha-v-integrins; Tgf-beta; Prognostic Biomarker; In-vivo; Expression; Pituitary; Peptide; Lung; Recognition; Target
Language
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 4673 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503800-001
DOI 10.1038/s41467-019-11863-w
WOS ID WOS:000489818900002
Scopus ID 85073182029
PubMed ID 31611594
Erfassungsdatum 2019-10-17
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