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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...

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Autores principales: Yao, Shaobo, Luo, Yaping, Zhang, Zhenzhong, Hu, Guilan, Zhu, Zhaohui, Li, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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.
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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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