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2 results on '"Guo, Haiwei Henry"'

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

Author

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, and Gambhir, Sanjiv S

Subjects
Humans, Neoplasms, Integrins, Antigens, Neoplasm, Positron-Emission Tomography, Magnetic Resonance Imaging, Crystallography, X-Ray, Idiopathic Pulmonary Fibrosis, Healthy Volunteers, Antigens, Neoplasm, Crystallography, X-Ray, Clinical Research, Bioengineering, Rare Diseases, Biomedical Imaging, Cancer, Lung, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies
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.

Published
2019

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

Author

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, and Gambhir, Sanjiv S

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Orphan Drug, Biomedical Imaging, Rare Diseases, Bioengineering, Cancer, Lung, 2.1 Biological and endogenous factors, Antigens, Neoplasm, Crystallography, X-Ray, Healthy Volunteers, Humans, Idiopathic Pulmonary Fibrosis, Integrins, Magnetic Resonance Imaging, Neoplasms, Positron-Emission Tomography
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.

Published
2019

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