Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature communications, 2019-10, Vol.10 (1), p.1-18, Article 4673

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 αvβ 6 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 α v β 6 .