Cysteine Derivatized <sup>99m</sup>Tc-Labelled Fatty Acids as β-Oxidation Markers
With the aim of developing <sup>99m</sup>Tc-labeled fatty acids intended for myocardial metabolism imaging we report herein the synthesis and characterization of two novel derivatives of undecanonoic and hexadecanonoic acid that have been functionalized at the ω-site by cysteine...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-11-01
|
| Series: | Inorganics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2304-6740/7/11/133 |
| _version_ | 1818180625262182400 |
|---|---|
| author | Theodoros Tsotakos Charalambos Triantis Christos Kiritsis Aggeliki Panagiotopoulou Dimitrios Psimadas Patricia Kyprianidou Maria Pelecanou Minas Papadopoulos Ioannis Pirmettis |
| author_facet | Theodoros Tsotakos Charalambos Triantis Christos Kiritsis Aggeliki Panagiotopoulou Dimitrios Psimadas Patricia Kyprianidou Maria Pelecanou Minas Papadopoulos Ioannis Pirmettis |
| author_sort | Theodoros Tsotakos |
| collection | DOAJ |
| description | With the aim of developing <sup>99m</sup>Tc-labeled fatty acids intended for myocardial metabolism imaging we report herein the synthesis and characterization of two novel derivatives of undecanonoic and hexadecanonoic acid that have been functionalized at the ω-site by cysteine through the formation of a thioether bond (<b>Cys−FA11</b> and <b>Cys−FA16</b>). Equimolar amounts of each ligand and the [NEt<sub>4</sub>]<sub>2</sub>[Re(CO)<sub>3</sub>Br<sub>3</sub>] precursor generated the respective hexacoordinated neutral complexes in which the ligand coordinated to the metal through the SNO donor system of cysteine. The rhenium complexes were characterized by elemental analysis, IR and NMR spectroscopies. The analogous technetium-99m complexes, <b><sup>99m</sup>Tc−Cys−FA11</b> and <b><sup>99m</sup>Tc−Cys−FA16</b> were prepared by incubation of the ligand with the precursor [<sup>99m</sup>Tc(CO)<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>]<sup>+</sup> (radiochemical yield ≥98%). Their structure was established by comparative HPLC techniques. In vivo studies in mice showed high initial heart uptake for both <sup>99m</sup>Tc complexes (7.4 ± 0.53 and 7.07 ± 0.73 percentage of injected dose (%ID)/g at 1 min post injection. Rapid clearance (0.60 ± 0.02 %ID/g) was observed for <b><sup>99m</sup>Tc−Cys−FA11</b> while the clearance of the longer fatty acid <b><sup>99m</sup>Tc−Cys−FA16</b> was slower (2.31 ± 0.09 %ID/g at 15 min p.i.). Metabolite analysis study indicated that complexes were catabolized through the β-oxidation process. |
| first_indexed | 2024-12-11T21:22:44Z |
| format | Article |
| id | doaj.art-7f7b3723d8844bf3bfe10364141c3608 |
| institution | Directory Open Access Journal |
| issn | 2304-6740 |
| language | English |
| last_indexed | 2024-12-11T21:22:44Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Inorganics |
| spelling | doaj.art-7f7b3723d8844bf3bfe10364141c36082022-12-22T00:50:26ZengMDPI AGInorganics2304-67402019-11-0171113310.3390/inorganics7110133inorganics7110133Cysteine Derivatized <sup>99m</sup>Tc-Labelled Fatty Acids as β-Oxidation MarkersTheodoros Tsotakos0Charalambos Triantis1Christos Kiritsis2Aggeliki Panagiotopoulou3Dimitrios Psimadas4Patricia Kyprianidou5Maria Pelecanou6Minas Papadopoulos7Ioannis Pirmettis8Institute of Nuclear and Radiological Sciences and Technology, Energy & Safety, NCSR “Demokritos”, 15310 Athens, GreeceDepartment of Pharmacy, Frederick University, Nicosia 1036, CyprusInstitute of Nuclear and Radiological Sciences and Technology, Energy & Safety, NCSR “Demokritos”, 15310 Athens, GreeceInstitute of Biosciences & Applications, NCSR “Demokritos”, 15310 Athens, GreeceDepartment of Nuclear Medicine, University Hospital of Larissa, 41110 Larissa, GreeceInstitute of Nuclear and Radiological Sciences and Technology, Energy & Safety, NCSR “Demokritos”, 15310 Athens, GreeceInstitute of Biosciences & Applications, NCSR “Demokritos”, 15310 Athens, GreeceInstitute of Nuclear and Radiological Sciences and Technology, Energy & Safety, NCSR “Demokritos”, 15310 Athens, GreeceInstitute of Nuclear and Radiological Sciences and Technology, Energy & Safety, NCSR “Demokritos”, 15310 Athens, GreeceWith the aim of developing <sup>99m</sup>Tc-labeled fatty acids intended for myocardial metabolism imaging we report herein the synthesis and characterization of two novel derivatives of undecanonoic and hexadecanonoic acid that have been functionalized at the ω-site by cysteine through the formation of a thioether bond (<b>Cys−FA11</b> and <b>Cys−FA16</b>). Equimolar amounts of each ligand and the [NEt<sub>4</sub>]<sub>2</sub>[Re(CO)<sub>3</sub>Br<sub>3</sub>] precursor generated the respective hexacoordinated neutral complexes in which the ligand coordinated to the metal through the SNO donor system of cysteine. The rhenium complexes were characterized by elemental analysis, IR and NMR spectroscopies. The analogous technetium-99m complexes, <b><sup>99m</sup>Tc−Cys−FA11</b> and <b><sup>99m</sup>Tc−Cys−FA16</b> were prepared by incubation of the ligand with the precursor [<sup>99m</sup>Tc(CO)<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>]<sup>+</sup> (radiochemical yield ≥98%). Their structure was established by comparative HPLC techniques. In vivo studies in mice showed high initial heart uptake for both <sup>99m</sup>Tc complexes (7.4 ± 0.53 and 7.07 ± 0.73 percentage of injected dose (%ID)/g at 1 min post injection. Rapid clearance (0.60 ± 0.02 %ID/g) was observed for <b><sup>99m</sup>Tc−Cys−FA11</b> while the clearance of the longer fatty acid <b><sup>99m</sup>Tc−Cys−FA16</b> was slower (2.31 ± 0.09 %ID/g at 15 min p.i.). Metabolite analysis study indicated that complexes were catabolized through the β-oxidation process.https://www.mdpi.com/2304-6740/7/11/133technetium-99mrheniumfatty acidβ-oxidationradiopharmaceuticalsradiometals |
| spellingShingle | Theodoros Tsotakos Charalambos Triantis Christos Kiritsis Aggeliki Panagiotopoulou Dimitrios Psimadas Patricia Kyprianidou Maria Pelecanou Minas Papadopoulos Ioannis Pirmettis Cysteine Derivatized <sup>99m</sup>Tc-Labelled Fatty Acids as β-Oxidation Markers Inorganics technetium-99m rhenium fatty acid β-oxidation radiopharmaceuticals radiometals |
| title | Cysteine Derivatized <sup>99m</sup>Tc-Labelled Fatty Acids as β-Oxidation Markers |
| title_full | Cysteine Derivatized <sup>99m</sup>Tc-Labelled Fatty Acids as β-Oxidation Markers |
| title_fullStr | Cysteine Derivatized <sup>99m</sup>Tc-Labelled Fatty Acids as β-Oxidation Markers |
| title_full_unstemmed | Cysteine Derivatized <sup>99m</sup>Tc-Labelled Fatty Acids as β-Oxidation Markers |
| title_short | Cysteine Derivatized <sup>99m</sup>Tc-Labelled Fatty Acids as β-Oxidation Markers |
| title_sort | cysteine derivatized sup 99m sup tc labelled fatty acids as β oxidation markers |
| topic | technetium-99m rhenium fatty acid β-oxidation radiopharmaceuticals radiometals |
| url | https://www.mdpi.com/2304-6740/7/11/133 |
| work_keys_str_mv | AT theodorostsotakos cysteinederivatizedsup99msuptclabelledfattyacidsasboxidationmarkers AT charalambostriantis cysteinederivatizedsup99msuptclabelledfattyacidsasboxidationmarkers AT christoskiritsis cysteinederivatizedsup99msuptclabelledfattyacidsasboxidationmarkers AT aggelikipanagiotopoulou cysteinederivatizedsup99msuptclabelledfattyacidsasboxidationmarkers AT dimitriospsimadas cysteinederivatizedsup99msuptclabelledfattyacidsasboxidationmarkers AT patriciakyprianidou cysteinederivatizedsup99msuptclabelledfattyacidsasboxidationmarkers AT mariapelecanou cysteinederivatizedsup99msuptclabelledfattyacidsasboxidationmarkers AT minaspapadopoulos cysteinederivatizedsup99msuptclabelledfattyacidsasboxidationmarkers AT ioannispirmettis cysteinederivatizedsup99msuptclabelledfattyacidsasboxidationmarkers |