Ac-EAZY! Towards GMP-Compliant Module Syntheses of <sup>225</sup>Ac-Labeled Peptides for Clinical Application
The application of <sup>225</sup>Ac (half-life T<sub>1/2</sub> = 9.92 d) dramatically reduces the activity used for peptide receptor radionuclide therapy by a factor of 1000 in comparison to <sup>90</sup>Y, <sup>177</sup>Lu or <sup>188</sup>...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/7/652 |
| _version_ | 1827687162218283008 |
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| author | Marc Pretze Falk Kunkel Roswitha Runge Robert Freudenberg Anja Braune Holger Hartmann Uwe Schwarz Claudia Brogsitter Jörg Kotzerke |
| author_facet | Marc Pretze Falk Kunkel Roswitha Runge Robert Freudenberg Anja Braune Holger Hartmann Uwe Schwarz Claudia Brogsitter Jörg Kotzerke |
| author_sort | Marc Pretze |
| collection | DOAJ |
| description | The application of <sup>225</sup>Ac (half-life T<sub>1/2</sub> = 9.92 d) dramatically reduces the activity used for peptide receptor radionuclide therapy by a factor of 1000 in comparison to <sup>90</sup>Y, <sup>177</sup>Lu or <sup>188</sup>Re while maintaining the therapeutic outcome. Additionally, the range of alpha particles of <sup>225</sup>Ac and its daughter nuclides in tissue is much lower (47–85 μm for alpha energies E<sub>α</sub> = 5.8–8.4 MeV), which results in a very precise dose deposition within the tumor. DOTA-conjugated commercially available peptides used for endoradiotherapy, which can readily be labeled with <sup>177</sup>Lu or <sup>90</sup>Y, can also accommodate <sup>225</sup>Ac. The benefits are lower doses in normal tissue for the patient, dose reduction of the employees and environment and less shielding material. The low availability of <sup>225</sup>Ac activity is preventing its application in clinical practice. Overcoming this barrier would open a broad field of <sup>225</sup>Ac therapy. Independent which production pathway of <sup>225</sup>Ac proves the most feasible, the use of automated synthesis and feasible and reproducible patient doses are needed. The Modular-Lab EAZY is one example of a GMP-compliant system, and the cassettes used for synthesis are small. Therefore, also the waste after the synthesis can be minimized. In this work, two different automated setups with different purification systems are presented. In its final configuration, three masterbatches were performed on the ML EAZY for DOTA-TATE and PSMA-I&T, respectively, fulfilling all quality criteria with final radiochemical yields of 80–90% for the <sup>225</sup>Ac-labeled peptides. |
| first_indexed | 2024-03-10T09:28:56Z |
| format | Article |
| id | doaj.art-9cc0c69b7c7547ec823b24ac1bd82ce7 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T09:28:56Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-9cc0c69b7c7547ec823b24ac1bd82ce72023-11-22T04:39:38ZengMDPI AGPharmaceuticals1424-82472021-07-0114765210.3390/ph14070652Ac-EAZY! Towards GMP-Compliant Module Syntheses of <sup>225</sup>Ac-Labeled Peptides for Clinical ApplicationMarc Pretze0Falk Kunkel1Roswitha Runge2Robert Freudenberg3Anja Braune4Holger Hartmann5Uwe Schwarz6Claudia Brogsitter7Jörg Kotzerke8Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, GermanyEckert & Ziegler Eurotope, 13125 Berlin, GermanyDepartment of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, GermanyDepartment of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, GermanyDepartment of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, GermanyDepartment of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, GermanyEckert & Ziegler Radiopharma, 38110 Braunschweig, GermanyDepartment of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, GermanyDepartment of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, GermanyThe application of <sup>225</sup>Ac (half-life T<sub>1/2</sub> = 9.92 d) dramatically reduces the activity used for peptide receptor radionuclide therapy by a factor of 1000 in comparison to <sup>90</sup>Y, <sup>177</sup>Lu or <sup>188</sup>Re while maintaining the therapeutic outcome. Additionally, the range of alpha particles of <sup>225</sup>Ac and its daughter nuclides in tissue is much lower (47–85 μm for alpha energies E<sub>α</sub> = 5.8–8.4 MeV), which results in a very precise dose deposition within the tumor. DOTA-conjugated commercially available peptides used for endoradiotherapy, which can readily be labeled with <sup>177</sup>Lu or <sup>90</sup>Y, can also accommodate <sup>225</sup>Ac. The benefits are lower doses in normal tissue for the patient, dose reduction of the employees and environment and less shielding material. The low availability of <sup>225</sup>Ac activity is preventing its application in clinical practice. Overcoming this barrier would open a broad field of <sup>225</sup>Ac therapy. Independent which production pathway of <sup>225</sup>Ac proves the most feasible, the use of automated synthesis and feasible and reproducible patient doses are needed. The Modular-Lab EAZY is one example of a GMP-compliant system, and the cassettes used for synthesis are small. Therefore, also the waste after the synthesis can be minimized. In this work, two different automated setups with different purification systems are presented. In its final configuration, three masterbatches were performed on the ML EAZY for DOTA-TATE and PSMA-I&T, respectively, fulfilling all quality criteria with final radiochemical yields of 80–90% for the <sup>225</sup>Ac-labeled peptides.https://www.mdpi.com/1424-8247/14/7/652actinium-225TATEPSMAmodule synthesisendoradiotherapyGMP |
| spellingShingle | Marc Pretze Falk Kunkel Roswitha Runge Robert Freudenberg Anja Braune Holger Hartmann Uwe Schwarz Claudia Brogsitter Jörg Kotzerke Ac-EAZY! Towards GMP-Compliant Module Syntheses of <sup>225</sup>Ac-Labeled Peptides for Clinical Application Pharmaceuticals actinium-225 TATE PSMA module synthesis endoradiotherapy GMP |
| title | Ac-EAZY! Towards GMP-Compliant Module Syntheses of <sup>225</sup>Ac-Labeled Peptides for Clinical Application |
| title_full | Ac-EAZY! Towards GMP-Compliant Module Syntheses of <sup>225</sup>Ac-Labeled Peptides for Clinical Application |
| title_fullStr | Ac-EAZY! Towards GMP-Compliant Module Syntheses of <sup>225</sup>Ac-Labeled Peptides for Clinical Application |
| title_full_unstemmed | Ac-EAZY! Towards GMP-Compliant Module Syntheses of <sup>225</sup>Ac-Labeled Peptides for Clinical Application |
| title_short | Ac-EAZY! Towards GMP-Compliant Module Syntheses of <sup>225</sup>Ac-Labeled Peptides for Clinical Application |
| title_sort | ac eazy towards gmp compliant module syntheses of sup 225 sup ac labeled peptides for clinical application |
| topic | actinium-225 TATE PSMA module synthesis endoradiotherapy GMP |
| url | https://www.mdpi.com/1424-8247/14/7/652 |
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