177Lu Radiolabeling of RM26 Modified with Oligo-Phenylene-Ethynylene and its Cellular Internalization
Gastrin releasing peptide receptor (GRPR) is overexpressed in various tumors, and these GRPR-positive tumors have successfully and widely been targeted with GRPR antagonists. To achieve a good therapeutic effectiveness and less radioactive dosage administration, high cellular internalization is requ...
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| Format: | Article |
| Language: | zho |
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Editorial Board of Journal of Isotopes
2022-06-01
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| Series: | Journal of Isotopes |
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| Online Access: | http://www.tws.org.cn/CN/10.7538/tws.2022.35.03.0200 |
| _version_ | 1811220056705597440 |
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| author | LIAO Wei;FU Huaxia;LI Xiangyu;KAN Wentao;YANG Xia;WANG Jing;ZHAO Peng;ZHUO Liangang;YANG Yuchuan;WEI Hongyuan |
| author_facet | LIAO Wei;FU Huaxia;LI Xiangyu;KAN Wentao;YANG Xia;WANG Jing;ZHAO Peng;ZHUO Liangang;YANG Yuchuan;WEI Hongyuan |
| author_sort | LIAO Wei;FU Huaxia;LI Xiangyu;KAN Wentao;YANG Xia;WANG Jing;ZHAO Peng;ZHUO Liangang;YANG Yuchuan;WEI Hongyuan |
| collection | DOAJ |
| description | Gastrin releasing peptide receptor (GRPR) is overexpressed in various tumors, and these GRPR-positive tumors have successfully and widely been targeted with GRPR antagonists. To achieve a good therapeutic effectiveness and less radioactive dosage administration, high cellular internalization is required. The cellular internalization of agonists is better than that of antagonists, but the severe side effects of agonists restrict their applications. In this study, we hypothesized that introducing membrane penetrating oligo-phenylene-ethynylene (OPE) to GRPR antagonist RM26 could increase the cellular internalization of antagonists. Therefore, two multi-functional compounds NOTA-OPE-1-RM26 and NOTA-OPE-2-RM26 were synthesized and labelled with 177Lu with high efficiency. The 177Lu labelled compounds 177Lu-NOTA-OPEs-RM26 were stable in saline, dulbecco’s modified eagle medium (DMEM) and newborn bovine serum. The in vitro experimental results indicated that the introduction of OPE-1 slightly increased the cellular internalization of the radiolabelled compounds while OPE-2 significantly increased the cellular internalization. In addition, the introduction of OPEs did not change the specific binding ability of RM26. The investigations indicated that introducing the OPE to increase the internalization was feasible. |
| first_indexed | 2024-04-12T07:35:26Z |
| format | Article |
| id | doaj.art-27b6dea3d5944f0081d556553e911bb2 |
| institution | Directory Open Access Journal |
| issn | 1000-7512 |
| language | zho |
| last_indexed | 2024-04-12T07:35:26Z |
| publishDate | 2022-06-01 |
| publisher | Editorial Board of Journal of Isotopes |
| record_format | Article |
| series | Journal of Isotopes |
| spelling | doaj.art-27b6dea3d5944f0081d556553e911bb22022-12-22T03:41:56ZzhoEditorial Board of Journal of IsotopesJournal of Isotopes1000-75122022-06-01353200208177Lu Radiolabeling of RM26 Modified with Oligo-Phenylene-Ethynylene and its Cellular InternalizationLIAO Wei;FU Huaxia;LI Xiangyu;KAN Wentao;YANG Xia;WANG Jing;ZHAO Peng;ZHUO Liangang;YANG Yuchuan;WEI Hongyuan0Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics；Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical UniversityGastrin releasing peptide receptor (GRPR) is overexpressed in various tumors, and these GRPR-positive tumors have successfully and widely been targeted with GRPR antagonists. To achieve a good therapeutic effectiveness and less radioactive dosage administration, high cellular internalization is required. The cellular internalization of agonists is better than that of antagonists, but the severe side effects of agonists restrict their applications. In this study, we hypothesized that introducing membrane penetrating oligo-phenylene-ethynylene (OPE) to GRPR antagonist RM26 could increase the cellular internalization of antagonists. Therefore, two multi-functional compounds NOTA-OPE-1-RM26 and NOTA-OPE-2-RM26 were synthesized and labelled with 177Lu with high efficiency. The 177Lu labelled compounds 177Lu-NOTA-OPEs-RM26 were stable in saline, dulbecco’s modified eagle medium (DMEM) and newborn bovine serum. The in vitro experimental results indicated that the introduction of OPE-1 slightly increased the cellular internalization of the radiolabelled compounds while OPE-2 significantly increased the cellular internalization. In addition, the introduction of OPEs did not change the specific binding ability of RM26. The investigations indicated that introducing the OPE to increase the internalization was feasible.http://www.tws.org.cn/CN/10.7538/tws.2022.35.03.0200177lurm26 peptideoligo-phenylene-ethynyleneinternalization |
| spellingShingle | LIAO Wei;FU Huaxia;LI Xiangyu;KAN Wentao;YANG Xia;WANG Jing;ZHAO Peng;ZHUO Liangang;YANG Yuchuan;WEI Hongyuan 177Lu Radiolabeling of RM26 Modified with Oligo-Phenylene-Ethynylene and its Cellular Internalization Journal of Isotopes 177lu rm26 peptide oligo-phenylene-ethynylene internalization |
| title | 177Lu Radiolabeling of RM26 Modified with Oligo-Phenylene-Ethynylene and its Cellular Internalization |
| title_full | 177Lu Radiolabeling of RM26 Modified with Oligo-Phenylene-Ethynylene and its Cellular Internalization |
| title_fullStr | 177Lu Radiolabeling of RM26 Modified with Oligo-Phenylene-Ethynylene and its Cellular Internalization |
| title_full_unstemmed | 177Lu Radiolabeling of RM26 Modified with Oligo-Phenylene-Ethynylene and its Cellular Internalization |
| title_short | 177Lu Radiolabeling of RM26 Modified with Oligo-Phenylene-Ethynylene and its Cellular Internalization |
| title_sort | 177lu radiolabeling of rm26 modified with oligo phenylene ethynylene and its cellular internalization |
| topic | 177lu rm26 peptide oligo-phenylene-ethynylene internalization |
| url | http://www.tws.org.cn/CN/10.7538/tws.2022.35.03.0200 |
| work_keys_str_mv | AT liaoweifuhuaxialixiangyukanwentaoyangxiawangjingzhaopengzhuoliangangyangyuchuanweihongyuan 177luradiolabelingofrm26modifiedwitholigophenyleneethynyleneanditscellularinternalization |