Cargando…

A Preliminary Study of PSMA Fluorescent Probe for Targeted Fluorescence Imaging of Prostate Cancer

Purpose: With the increasing detection rate of early prostate cancer (PCa), the proportion of surgical treatment is increasing. Surgery is the most effective treatment for PCa. Precise targeting of tumors during surgery can reduce the incidence of positive surgical margins (PSMs) and preserve the ne...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Haoxi, Liu, Yachao, Zhang, Xiaojun, Chen, Kuang, Li, Yuan, Xu, Xiaodan, Xu, Baixuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099975/
https://www.ncbi.nlm.nih.gov/pubmed/35566085
http://dx.doi.org/10.3390/molecules27092736
_version_ 1784706739400081408
author Zhou, Haoxi
Liu, Yachao
Zhang, Xiaojun
Chen, Kuang
Li, Yuan
Xu, Xiaodan
Xu, Baixuan
author_facet Zhou, Haoxi
Liu, Yachao
Zhang, Xiaojun
Chen, Kuang
Li, Yuan
Xu, Xiaodan
Xu, Baixuan
author_sort Zhou, Haoxi
collection PubMed
description Purpose: With the increasing detection rate of early prostate cancer (PCa), the proportion of surgical treatment is increasing. Surgery is the most effective treatment for PCa. Precise targeting of tumors during surgery can reduce the incidence of positive surgical margins (PSMs) and preserve the neurovascular bundles (NVBs) as much as possible. The objective of this study was to synthesize a PSMA fluorescent probe (PSMA-Cy5) and verify the targeting specificity of the probe for prostate cancer, thereby providing a theoretical basis for the development of PSMA fluorescent probes for clinical application in the future. Methods: In this study, a novel water-soluble 3H-indocyanine-type bioluminescent dye-Cy5-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-Cy5) was synthesized by liquid phase synthesis. The PSMA ligand was developed based on the glutamine-urea-lysine (Glu-urea-Lys) structure. The new fluorescent probe was evaluated in vitro and in vivo, and its safety was evaluated. Confocal microscopy was used to observe the binding uptake of PSMA-Cy5 with PSMA (+) LNCaP cells, PSMA (-) PC3 cells and blocked LNCaP cells. In in vivo optical imaging studies, the targeting specificity of PSMA (+) 22Rv1 tumors to probe binding was validated by tail vein injection of PSMA-Cy5. The safety of the PSMA-Cy5 probe was evaluated by histopathological analysis of mouse organs by a single high-dose tail vein injection of PSMA-Cy5. Results: In vitro fluorescence cell uptake experiments showed that the binding of PSMA-Cy5 to LNCaP cells has targeting specificity. PC3 cells and blocked LNCaP cells showed almost no uptake. The results of in vivo optical imaging studies showed that the tumor-to-background ratio in the 22Rv1 group was 3.39 ± 0.47; in the 22Rv1 blocking group it was 0.78 ± 0.15, and in the PC3 group it was 0.94 ± 0.09, consistent with the in vitro results. After a high-dose injection of PSMA-Cy5, there were no abnormalities in the tissues or organs of the mice. The probe showed good safety. Conclusions: PSMA-Cy5 is a probe with good targeting specificity and low toxicity that can accurately visualize tumors in vivo. This study has an important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to precise tumor imaging during radical prostatectomy to reduce the incidence of postoperative PSM.
format Online
Article
Text
id pubmed-9099975
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90999752022-05-14 A Preliminary Study of PSMA Fluorescent Probe for Targeted Fluorescence Imaging of Prostate Cancer Zhou, Haoxi Liu, Yachao Zhang, Xiaojun Chen, Kuang Li, Yuan Xu, Xiaodan Xu, Baixuan Molecules Article Purpose: With the increasing detection rate of early prostate cancer (PCa), the proportion of surgical treatment is increasing. Surgery is the most effective treatment for PCa. Precise targeting of tumors during surgery can reduce the incidence of positive surgical margins (PSMs) and preserve the neurovascular bundles (NVBs) as much as possible. The objective of this study was to synthesize a PSMA fluorescent probe (PSMA-Cy5) and verify the targeting specificity of the probe for prostate cancer, thereby providing a theoretical basis for the development of PSMA fluorescent probes for clinical application in the future. Methods: In this study, a novel water-soluble 3H-indocyanine-type bioluminescent dye-Cy5-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-Cy5) was synthesized by liquid phase synthesis. The PSMA ligand was developed based on the glutamine-urea-lysine (Glu-urea-Lys) structure. The new fluorescent probe was evaluated in vitro and in vivo, and its safety was evaluated. Confocal microscopy was used to observe the binding uptake of PSMA-Cy5 with PSMA (+) LNCaP cells, PSMA (-) PC3 cells and blocked LNCaP cells. In in vivo optical imaging studies, the targeting specificity of PSMA (+) 22Rv1 tumors to probe binding was validated by tail vein injection of PSMA-Cy5. The safety of the PSMA-Cy5 probe was evaluated by histopathological analysis of mouse organs by a single high-dose tail vein injection of PSMA-Cy5. Results: In vitro fluorescence cell uptake experiments showed that the binding of PSMA-Cy5 to LNCaP cells has targeting specificity. PC3 cells and blocked LNCaP cells showed almost no uptake. The results of in vivo optical imaging studies showed that the tumor-to-background ratio in the 22Rv1 group was 3.39 ± 0.47; in the 22Rv1 blocking group it was 0.78 ± 0.15, and in the PC3 group it was 0.94 ± 0.09, consistent with the in vitro results. After a high-dose injection of PSMA-Cy5, there were no abnormalities in the tissues or organs of the mice. The probe showed good safety. Conclusions: PSMA-Cy5 is a probe with good targeting specificity and low toxicity that can accurately visualize tumors in vivo. This study has an important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to precise tumor imaging during radical prostatectomy to reduce the incidence of postoperative PSM. MDPI 2022-04-24 /pmc/articles/PMC9099975/ /pubmed/35566085 http://dx.doi.org/10.3390/molecules27092736 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhou, Haoxi
Liu, Yachao
Zhang, Xiaojun
Chen, Kuang
Li, Yuan
Xu, Xiaodan
Xu, Baixuan
A Preliminary Study of PSMA Fluorescent Probe for Targeted Fluorescence Imaging of Prostate Cancer
title A Preliminary Study of PSMA Fluorescent Probe for Targeted Fluorescence Imaging of Prostate Cancer
title_full A Preliminary Study of PSMA Fluorescent Probe for Targeted Fluorescence Imaging of Prostate Cancer
title_fullStr A Preliminary Study of PSMA Fluorescent Probe for Targeted Fluorescence Imaging of Prostate Cancer
title_full_unstemmed A Preliminary Study of PSMA Fluorescent Probe for Targeted Fluorescence Imaging of Prostate Cancer
title_short A Preliminary Study of PSMA Fluorescent Probe for Targeted Fluorescence Imaging of Prostate Cancer
title_sort preliminary study of psma fluorescent probe for targeted fluorescence imaging of prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099975/
https://www.ncbi.nlm.nih.gov/pubmed/35566085
http://dx.doi.org/10.3390/molecules27092736
work_keys_str_mv AT zhouhaoxi apreliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT liuyachao apreliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT zhangxiaojun apreliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT chenkuang apreliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT liyuan apreliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT xuxiaodan apreliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT xubaixuan apreliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT zhouhaoxi preliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT liuyachao preliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT zhangxiaojun preliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT chenkuang preliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT liyuan preliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT xuxiaodan preliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer
AT xubaixuan preliminarystudyofpsmafluorescentprobefortargetedfluorescenceimagingofprostatecancer