Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours
Isocitrate dehydrogenases (IDHs) are metabolic enzymes commonly mutated in human cancers (glioma, acute myeloid leukaemia, chondrosarcoma, and intrahepatic cholangiocarcinoma). These mutated variants of IDH (mIDH) acquire a neomorphic activity, namely, conversion of α-ketoglutarate to the oncometabo...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/12/3766 |
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| author | Valérie Weber Lucie Arnaud Sladjana Dukic-Stefanovic Barbara Wenzel Valérie Roux Jean-Michel Chezal Thu-Hang Lai Rodrigo Teodoro Klaus Kopka Elisabeth Miot-Noirault Winnie Deuther-Conrad Aurélie Maisonial-Besset |
| author_facet | Valérie Weber Lucie Arnaud Sladjana Dukic-Stefanovic Barbara Wenzel Valérie Roux Jean-Michel Chezal Thu-Hang Lai Rodrigo Teodoro Klaus Kopka Elisabeth Miot-Noirault Winnie Deuther-Conrad Aurélie Maisonial-Besset |
| author_sort | Valérie Weber |
| collection | DOAJ |
| description | Isocitrate dehydrogenases (IDHs) are metabolic enzymes commonly mutated in human cancers (glioma, acute myeloid leukaemia, chondrosarcoma, and intrahepatic cholangiocarcinoma). These mutated variants of IDH (mIDH) acquire a neomorphic activity, namely, conversion of α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate involved in tumourigenesis. Thus, mIDHs have emerged as highly promising therapeutic targets, and several mIDH specific inhibitors have been developed. However, the evaluation of mIDH status, currently performed by biopsy, is essential for patient stratification and thus treatment and follow-up. We report herein the development of new radioiodinated and radiofluorinated analogues of olutasidenib (FT-2102) as tools for noninvasive single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging of mIDH1 up- and dysregulation in tumours. Nonradiolabelled derivatives <b>2</b> and <b>3</b> halogenated at position 6 of the quinolinone scaffold were synthesised and tested in vitro for their inhibitory potencies and selectivities in comparison with the lead compound FT-2102. Using a common organotin precursor, (<i>S</i>)-[<sup>125</sup>I]<b>2</b> and (<i>S</i>)-[<sup>18</sup>F]<b>3</b> were efficiently synthesised by radio-iododemetallation and copper-mediated radiofluorination, respectively. Both radiotracers were stable at room temperature in saline or DPBS solution and at 37 °C in mouse serum, allowing future planning of their in vitro and in vivo evaluations in glioma and chondrosarcoma models. |
| first_indexed | 2024-03-09T22:56:34Z |
| format | Article |
| id | doaj.art-d2c3674b007a4d6ea932059eb464d1ec |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T22:56:34Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-d2c3674b007a4d6ea932059eb464d1ec2023-11-23T18:10:59ZengMDPI AGMolecules1420-30492022-06-012712376610.3390/molecules27123766Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant TumoursValérie Weber0Lucie Arnaud1Sladjana Dukic-Stefanovic2Barbara Wenzel3Valérie Roux4Jean-Michel Chezal5Thu-Hang Lai6Rodrigo Teodoro7Klaus Kopka8Elisabeth Miot-Noirault9Winnie Deuther-Conrad10Aurélie Maisonial-Besset11Université Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, 04318 Leipzig, GermanyHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, 04318 Leipzig, GermanyUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, 04318 Leipzig, GermanyHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, 04318 Leipzig, GermanyHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, 04318 Leipzig, GermanyUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, 04318 Leipzig, GermanyUniversité Clermont Auvergne, Inserm, Imagerie Moléculaire et Stratégies Théranostiques, UMR 1240, F-63000 Clermont-Ferrand, FranceIsocitrate dehydrogenases (IDHs) are metabolic enzymes commonly mutated in human cancers (glioma, acute myeloid leukaemia, chondrosarcoma, and intrahepatic cholangiocarcinoma). These mutated variants of IDH (mIDH) acquire a neomorphic activity, namely, conversion of α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate involved in tumourigenesis. Thus, mIDHs have emerged as highly promising therapeutic targets, and several mIDH specific inhibitors have been developed. However, the evaluation of mIDH status, currently performed by biopsy, is essential for patient stratification and thus treatment and follow-up. We report herein the development of new radioiodinated and radiofluorinated analogues of olutasidenib (FT-2102) as tools for noninvasive single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging of mIDH1 up- and dysregulation in tumours. Nonradiolabelled derivatives <b>2</b> and <b>3</b> halogenated at position 6 of the quinolinone scaffold were synthesised and tested in vitro for their inhibitory potencies and selectivities in comparison with the lead compound FT-2102. Using a common organotin precursor, (<i>S</i>)-[<sup>125</sup>I]<b>2</b> and (<i>S</i>)-[<sup>18</sup>F]<b>3</b> were efficiently synthesised by radio-iododemetallation and copper-mediated radiofluorination, respectively. Both radiotracers were stable at room temperature in saline or DPBS solution and at 37 °C in mouse serum, allowing future planning of their in vitro and in vivo evaluations in glioma and chondrosarcoma models.https://www.mdpi.com/1420-3049/27/12/3766SPECT/PET imagingmIDH1FT-2102radioiodinationradiofluorination |
| spellingShingle | Valérie Weber Lucie Arnaud Sladjana Dukic-Stefanovic Barbara Wenzel Valérie Roux Jean-Michel Chezal Thu-Hang Lai Rodrigo Teodoro Klaus Kopka Elisabeth Miot-Noirault Winnie Deuther-Conrad Aurélie Maisonial-Besset Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours Molecules SPECT/PET imaging mIDH1 FT-2102 radioiodination radiofluorination |
| title | Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours |
| title_full | Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours |
| title_fullStr | Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours |
| title_full_unstemmed | Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours |
| title_short | Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours |
| title_sort | novel radioiodinated and radiofluorinated analogues of ft 2102 for spect or pet imaging of midh1 mutant tumours |
| topic | SPECT/PET imaging mIDH1 FT-2102 radioiodination radiofluorination |
| url | https://www.mdpi.com/1420-3049/27/12/3766 |
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