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

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. Ou

SUBMITTER: Kimura RH 

PROVIDER: S-EPMC6791878 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature