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Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose
PURPOSE: This study aims at preclinical evaluation of a recently reported lactose analogue, 1'-(18)F-fluoroethyl-β-D-lactose ((18)F-FEL), in binding to hepatocarcinoma-intestine-pancreas and pancreatitis-associated protein (HIP/PAP) in vitro and in vivo. METHODS: In this study, a multifunctiona...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650409/ https://www.ncbi.nlm.nih.gov/pubmed/29088854 http://dx.doi.org/10.18632/oncotarget.20654 |
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author | Yao, Shaobo Luo, Yaping Zhang, Zhenzhong Hu, Guilan Zhu, Zhaohui Li, Fang |
author_facet | Yao, Shaobo Luo, Yaping Zhang, Zhenzhong Hu, Guilan Zhu, Zhaohui Li, Fang |
author_sort | Yao, Shaobo |
collection | PubMed |
description | PURPOSE: This study aims at preclinical evaluation of a recently reported lactose analogue, 1'-(18)F-fluoroethyl-β-D-lactose ((18)F-FEL), in binding to hepatocarcinoma-intestine-pancreas and pancreatitis-associated protein (HIP/PAP) in vitro and in vivo. METHODS: In this study, a multifunctional module was employed for the automated synthesis of (18)F-FEL. Additional radiochemical purity, biodistribution, in vitro and in vivo competition, metabolic stability and micro-PET studies were performed using T3M4 and SK-BR-3 xenografts. Expression of HIP/PAP in T3M4 and SK-BR-3 tumor sections and cell lines were tested with immunohistochemistry (IHC) and western blot analysis. RESULTS: The synthesis of (18)F-FEL was completed in 30 min, with a radiochemical yield of 20 ± 5% and specific activity of 14.2 ± 7.1 GBq/μmol. (18)F-FEL exhibited high HIP/PAP-binding affinity with a half maximal inhibitory concentration (IC50) of 22.0 ± 4.0 nM. (18)F-FEL demonstrated high stability and specific tumor accumulation, which was reduced by approximately 80% in a PET competition assay by co-injection of β-D-lactose. High expression of HIP/PAP was detected in T3M4 tumors and cell line, but negative result was found for SK-BR-3 cell line. CONCLUSION: (18)F-FEL has a high binding property to HIP/PAP, high stability and excellent pharmacokinetics in vivo and therefore warrants further evaluation in a proof-of-concept study in humans. |
format | Online Article Text |
id | pubmed-5650409 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56504092017-10-30 Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose Yao, Shaobo Luo, Yaping Zhang, Zhenzhong Hu, Guilan Zhu, Zhaohui Li, Fang Oncotarget Research Paper PURPOSE: This study aims at preclinical evaluation of a recently reported lactose analogue, 1'-(18)F-fluoroethyl-β-D-lactose ((18)F-FEL), in binding to hepatocarcinoma-intestine-pancreas and pancreatitis-associated protein (HIP/PAP) in vitro and in vivo. METHODS: In this study, a multifunctional module was employed for the automated synthesis of (18)F-FEL. Additional radiochemical purity, biodistribution, in vitro and in vivo competition, metabolic stability and micro-PET studies were performed using T3M4 and SK-BR-3 xenografts. Expression of HIP/PAP in T3M4 and SK-BR-3 tumor sections and cell lines were tested with immunohistochemistry (IHC) and western blot analysis. RESULTS: The synthesis of (18)F-FEL was completed in 30 min, with a radiochemical yield of 20 ± 5% and specific activity of 14.2 ± 7.1 GBq/μmol. (18)F-FEL exhibited high HIP/PAP-binding affinity with a half maximal inhibitory concentration (IC50) of 22.0 ± 4.0 nM. (18)F-FEL demonstrated high stability and specific tumor accumulation, which was reduced by approximately 80% in a PET competition assay by co-injection of β-D-lactose. High expression of HIP/PAP was detected in T3M4 tumors and cell line, but negative result was found for SK-BR-3 cell line. CONCLUSION: (18)F-FEL has a high binding property to HIP/PAP, high stability and excellent pharmacokinetics in vivo and therefore warrants further evaluation in a proof-of-concept study in humans. Impact Journals LLC 2017-09-06 /pmc/articles/PMC5650409/ /pubmed/29088854 http://dx.doi.org/10.18632/oncotarget.20654 Text en Copyright: © 2017 Yao et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Yao, Shaobo Luo, Yaping Zhang, Zhenzhong Hu, Guilan Zhu, Zhaohui Li, Fang Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose |
title | Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose |
title_full | Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose |
title_fullStr | Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose |
title_full_unstemmed | Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose |
title_short | Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose |
title_sort | preclinical pet imaging of hip/pap using 1'-(18)f-fluoroethyl-β-d-lactose |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650409/ https://www.ncbi.nlm.nih.gov/pubmed/29088854 http://dx.doi.org/10.18632/oncotarget.20654 |
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