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Synthesis and Evaluation of (18)F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging

The gonadotropin-releasing hormone (GnRH) receptor is overexpressed in the majority of tumors of the human reproductive system. The purpose of this study was to develop an (18)F-labeled peptide for tumor GnRH receptor imaging. In this study, the GnRH (pGlu(1)-His(2)-Trp(3)-Ser(4)-Tyr(5)-Gly(6)-Leu(7...

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Autores principales: Huang, Shun, Li, Hongsheng, Han, Yanjiang, Fu, Lilan, Ren, Yunyan, Zhang, Yin, Li, Youcai, Sun, Penghui, Wang, Meng, Wu, Hubing, Wang, Quanshi, Hu, Kongzhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431521/
https://www.ncbi.nlm.nih.gov/pubmed/30983920
http://dx.doi.org/10.1155/2019/5635269
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author Huang, Shun
Li, Hongsheng
Han, Yanjiang
Fu, Lilan
Ren, Yunyan
Zhang, Yin
Li, Youcai
Sun, Penghui
Wang, Meng
Wu, Hubing
Wang, Quanshi
Hu, Kongzhen
author_facet Huang, Shun
Li, Hongsheng
Han, Yanjiang
Fu, Lilan
Ren, Yunyan
Zhang, Yin
Li, Youcai
Sun, Penghui
Wang, Meng
Wu, Hubing
Wang, Quanshi
Hu, Kongzhen
author_sort Huang, Shun
collection PubMed
description The gonadotropin-releasing hormone (GnRH) receptor is overexpressed in the majority of tumors of the human reproductive system. The purpose of this study was to develop an (18)F-labeled peptide for tumor GnRH receptor imaging. In this study, the GnRH (pGlu(1)-His(2)-Trp(3)-Ser(4)-Tyr(5)-Gly(6)-Leu(7)-Arg(8)-Pro(9)-Gly(10)-NH(2)) peptide analogues FP-d-Lys(6)-GnRH (FP = 2-fluoropropanoyl) and NOTA-P-d-Lys(6)-GnRH (P = ethylene glycol) were designed and synthesized. The IC(50) values of FP-d-Lys(6)-GnRH and NOTA-P-d-Lys(6)-GnRH were 2.0 nM and 56.2 nM, respectively. 4-Nitrophenyl-2-[(18)F]fluoropropionate was conjugated to the ε-amino group of the d-lysine side chain of d-Lys(6)-GnRH to yield the new tracer [(18)F]FP-d-Lys(6)-GnRH with a decay-corrected yield of 8 ± 3% and a specific activity of 20−100 GBq/µmol (n=6). Cell uptake studies of [(18)F]FP-d-Lys(6)-GnRH in GnRH receptor-positive PC-3 cells and GnRH receptor-negative CHO-K1 cells indicated receptor-specific accumulation. Biodistribution and PET studies in nude mice bearing PC-3 xenografted tumors showed that [(18)F]FP-d-Lys(6)-GnRH was localized in tumors with a higher uptake than in surrounding muscle and heart tissues. Furthermore, the metabolic stability of [(18)F]FP-d-Lys(6)-GnRH was determined in mouse blood and PC-3 tumor homogenates at 1 h after tracer injection. The presented results indicated a potential of the novel tracer [(18)F]FP-d-Lys(6)-GnRH for tumor GnRH receptor imaging.
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spelling pubmed-64315212019-04-14 Synthesis and Evaluation of (18)F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging Huang, Shun Li, Hongsheng Han, Yanjiang Fu, Lilan Ren, Yunyan Zhang, Yin Li, Youcai Sun, Penghui Wang, Meng Wu, Hubing Wang, Quanshi Hu, Kongzhen Contrast Media Mol Imaging Research Article The gonadotropin-releasing hormone (GnRH) receptor is overexpressed in the majority of tumors of the human reproductive system. The purpose of this study was to develop an (18)F-labeled peptide for tumor GnRH receptor imaging. In this study, the GnRH (pGlu(1)-His(2)-Trp(3)-Ser(4)-Tyr(5)-Gly(6)-Leu(7)-Arg(8)-Pro(9)-Gly(10)-NH(2)) peptide analogues FP-d-Lys(6)-GnRH (FP = 2-fluoropropanoyl) and NOTA-P-d-Lys(6)-GnRH (P = ethylene glycol) were designed and synthesized. The IC(50) values of FP-d-Lys(6)-GnRH and NOTA-P-d-Lys(6)-GnRH were 2.0 nM and 56.2 nM, respectively. 4-Nitrophenyl-2-[(18)F]fluoropropionate was conjugated to the ε-amino group of the d-lysine side chain of d-Lys(6)-GnRH to yield the new tracer [(18)F]FP-d-Lys(6)-GnRH with a decay-corrected yield of 8 ± 3% and a specific activity of 20−100 GBq/µmol (n=6). Cell uptake studies of [(18)F]FP-d-Lys(6)-GnRH in GnRH receptor-positive PC-3 cells and GnRH receptor-negative CHO-K1 cells indicated receptor-specific accumulation. Biodistribution and PET studies in nude mice bearing PC-3 xenografted tumors showed that [(18)F]FP-d-Lys(6)-GnRH was localized in tumors with a higher uptake than in surrounding muscle and heart tissues. Furthermore, the metabolic stability of [(18)F]FP-d-Lys(6)-GnRH was determined in mouse blood and PC-3 tumor homogenates at 1 h after tracer injection. The presented results indicated a potential of the novel tracer [(18)F]FP-d-Lys(6)-GnRH for tumor GnRH receptor imaging. Hindawi 2019-03-07 /pmc/articles/PMC6431521/ /pubmed/30983920 http://dx.doi.org/10.1155/2019/5635269 Text en Copyright © 2019 Shun Huang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Huang, Shun
Li, Hongsheng
Han, Yanjiang
Fu, Lilan
Ren, Yunyan
Zhang, Yin
Li, Youcai
Sun, Penghui
Wang, Meng
Wu, Hubing
Wang, Quanshi
Hu, Kongzhen
Synthesis and Evaluation of (18)F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging
title Synthesis and Evaluation of (18)F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging
title_full Synthesis and Evaluation of (18)F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging
title_fullStr Synthesis and Evaluation of (18)F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging
title_full_unstemmed Synthesis and Evaluation of (18)F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging
title_short Synthesis and Evaluation of (18)F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging
title_sort synthesis and evaluation of (18)f-labeled peptide for gonadotropin-releasing hormone receptor imaging
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431521/
https://www.ncbi.nlm.nih.gov/pubmed/30983920
http://dx.doi.org/10.1155/2019/5635269
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