King's College London

Research portal

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

Research output: Contribution to journalArticle

Richard H Kimura, Ling Wang, Bin Shen, Li Huo, Willemieke Tummers, Fabian V Filipp, Haiwei Henry Guo, Thomas Haywood, Lotfi Abou-Elkacem, Lucia Baratto, Frezghi Habte, Rammohan Devulapally, Timothy H Witney, Yan Cheng, Suhas Tikole, Subhendu Chakraborti, Jay Nix, Christopher A Bonagura, Negin Hatami, Joshua J Mooney & 22 more Tushar Desai, Scott Turner, Richard S Gaster, Andrea Otte, Brendan C Visser, George A Poultsides, Jeffrey Norton, Walter Park, Mark Stolowitz, Kenneth Lau, Eric Yang, Arutselvan Natarajan, Ohad Ilovich, Shyam Srinivas, Ananth Srinivasan, Ramasamy Paulmurugan, Juergen Willmann, Frederick T Chin, Zhen Cheng, Andrei Iagaru, Fang Li, Sanjiv S Gambhir

Original languageEnglish
Article number4673
Pages (from-to)4673
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Documents

  • s41467-019-11863-w

    s41467_019_11863_w.pdf, 9.06 MB, application/pdf

    22/10/2019

    Final published version

    CC BY

King's Authors

Abstract

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.

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454