Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases
Hyperlipidemia causes systemic lipid disorder, which leads to hepatic steatosis and atherosclerosis. Thus, it is necessary to detect these syndromes early and precisely to improve prognosis. In the affected regions, abnormal formation and growth of lipid droplets is observed; therefore, lipid drople...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-06-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/24/12/2283 |
| _version_ | 1818874066624315392 |
|---|---|
| author | Yoichi Shimizu Keiichi Tanimura Shimpei Iikuni Hiroyuki Watanabe Hideo Saji Masahiro Ono |
| author_facet | Yoichi Shimizu Keiichi Tanimura Shimpei Iikuni Hiroyuki Watanabe Hideo Saji Masahiro Ono |
| author_sort | Yoichi Shimizu |
| collection | DOAJ |
| description | Hyperlipidemia causes systemic lipid disorder, which leads to hepatic steatosis and atherosclerosis. Thus, it is necessary to detect these syndromes early and precisely to improve prognosis. In the affected regions, abnormal formation and growth of lipid droplets is observed; therefore, lipid droplets may be a suitable target for the diagnosis of hyperlipidemia-related syndromes. In this study, we designed and synthesized [<sup>99m</sup>Tc]Tc-BOD and [<sup>99m</sup>Tc]Tc-MBOD composed of one technetium-99m and two BODIPY scaffolds with hydroxamamide (Ham) or <i>N</i>-methylated hydroxamamide (MHam) in radiochemical yields of 54 and 35%, respectively, with a radiochemical purity of over 95%. [<sup>99m</sup>Tc]Tc-BOD showed significantly higher accumulation levels in foam cells than in non-foam cells (foam cells: 213.8 ± 64.8, non-foam cell: 126.2 ± 26.9 %dose/mg protein, <i>p</i> < 0.05) 2 h after incubation. In contrast, [<sup>99m</sup>Tc]Tc-MBOD showed similar accumulation levels in foam cells and non-foam cells (foam cells: 92.2 ± 23.3, non-foam cell: 83.8 ± 19.8 %dose/mg protein). In normal mice, [<sup>99m</sup>Tc]Tc-BOD exhibited gradual blood clearance (0.5 h: 4.98 ± 0.35, 6 h: 1.94 ± 0.12 %ID/g) and relatively high accumulation in the liver 6 h after administration (15.22 ± 1.72 %ID/g). Therefore, [<sup>99m</sup>Tc]Tc-BOD may have potential as an imaging probe for detecting lipid droplets in disease lesions of hyperlipidemia. |
| first_indexed | 2024-12-19T13:04:42Z |
| format | Article |
| id | doaj.art-4b71b2c17bc6494fa5e351362709e569 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-19T13:04:42Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4b71b2c17bc6494fa5e351362709e5692022-12-21T20:20:05ZengMDPI AGMolecules1420-30492019-06-012412228310.3390/molecules24122283molecules24122283Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related DiseasesYoichi Shimizu0Keiichi Tanimura1Shimpei Iikuni2Hiroyuki Watanabe3Hideo Saji4Masahiro Ono5Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46–29, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, JapanDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46–29, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, JapanDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46–29, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, JapanDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46–29, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, JapanDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46–29, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, JapanDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46–29, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, JapanHyperlipidemia causes systemic lipid disorder, which leads to hepatic steatosis and atherosclerosis. Thus, it is necessary to detect these syndromes early and precisely to improve prognosis. In the affected regions, abnormal formation and growth of lipid droplets is observed; therefore, lipid droplets may be a suitable target for the diagnosis of hyperlipidemia-related syndromes. In this study, we designed and synthesized [<sup>99m</sup>Tc]Tc-BOD and [<sup>99m</sup>Tc]Tc-MBOD composed of one technetium-99m and two BODIPY scaffolds with hydroxamamide (Ham) or <i>N</i>-methylated hydroxamamide (MHam) in radiochemical yields of 54 and 35%, respectively, with a radiochemical purity of over 95%. [<sup>99m</sup>Tc]Tc-BOD showed significantly higher accumulation levels in foam cells than in non-foam cells (foam cells: 213.8 ± 64.8, non-foam cell: 126.2 ± 26.9 %dose/mg protein, <i>p</i> < 0.05) 2 h after incubation. In contrast, [<sup>99m</sup>Tc]Tc-MBOD showed similar accumulation levels in foam cells and non-foam cells (foam cells: 92.2 ± 23.3, non-foam cell: 83.8 ± 19.8 %dose/mg protein). In normal mice, [<sup>99m</sup>Tc]Tc-BOD exhibited gradual blood clearance (0.5 h: 4.98 ± 0.35, 6 h: 1.94 ± 0.12 %ID/g) and relatively high accumulation in the liver 6 h after administration (15.22 ± 1.72 %ID/g). Therefore, [<sup>99m</sup>Tc]Tc-BOD may have potential as an imaging probe for detecting lipid droplets in disease lesions of hyperlipidemia.https://www.mdpi.com/1420-3049/24/12/2283technetium-99mhyperlipidemiahydroxamamideBODIPY |
| spellingShingle | Yoichi Shimizu Keiichi Tanimura Shimpei Iikuni Hiroyuki Watanabe Hideo Saji Masahiro Ono Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases Molecules technetium-99m hyperlipidemia hydroxamamide BODIPY |
| title | Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases |
| title_full | Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases |
| title_fullStr | Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases |
| title_full_unstemmed | Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases |
| title_short | Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases |
| title_sort | development of technetium 99m labeled bodipy based probes targeting lipid droplets toward the diagnosis of hyperlipidemia related diseases |
| topic | technetium-99m hyperlipidemia hydroxamamide BODIPY |
| url | https://www.mdpi.com/1420-3049/24/12/2283 |
| work_keys_str_mv | AT yoichishimizu developmentoftechnetium99mlabeledbodipybasedprobestargetinglipiddropletstowardthediagnosisofhyperlipidemiarelateddiseases AT keiichitanimura developmentoftechnetium99mlabeledbodipybasedprobestargetinglipiddropletstowardthediagnosisofhyperlipidemiarelateddiseases AT shimpeiiikuni developmentoftechnetium99mlabeledbodipybasedprobestargetinglipiddropletstowardthediagnosisofhyperlipidemiarelateddiseases AT hiroyukiwatanabe developmentoftechnetium99mlabeledbodipybasedprobestargetinglipiddropletstowardthediagnosisofhyperlipidemiarelateddiseases AT hideosaji developmentoftechnetium99mlabeledbodipybasedprobestargetinglipiddropletstowardthediagnosisofhyperlipidemiarelateddiseases AT masahiroono developmentoftechnetium99mlabeledbodipybasedprobestargetinglipiddropletstowardthediagnosisofhyperlipidemiarelateddiseases |