Radiosynthesis Standardization and Preclinical Assessment of the [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub>: A Translational Study Targeting Differential Diagnosis of Infectious Processes
Human bacterial infections significantly contribute to the increase in healthcare-related burdens. This scenario drives the study of novel techniques for the early and precise diagnosis of infectious processes. Some alternatives include Nuclear Medicine- and Molecular Imaging-based strategies. Howev...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/17/1/48 |
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| author | Ana Cláudia Camargo Miranda Leonardo Lima Fuscaldi Jorge Mejia Fábio Fernando Alves da Silva Walter Miguel Turato Fernanda Ferreira Mendonça Solange Amorim Nogueira Akemi Osawa Lilian Yuri Itaya Yamaga Luciana Malavolta Marycel Figols de Barboza |
| author_facet | Ana Cláudia Camargo Miranda Leonardo Lima Fuscaldi Jorge Mejia Fábio Fernando Alves da Silva Walter Miguel Turato Fernanda Ferreira Mendonça Solange Amorim Nogueira Akemi Osawa Lilian Yuri Itaya Yamaga Luciana Malavolta Marycel Figols de Barboza |
| author_sort | Ana Cláudia Camargo Miranda |
| collection | DOAJ |
| description | Human bacterial infections significantly contribute to the increase in healthcare-related burdens. This scenario drives the study of novel techniques for the early and precise diagnosis of infectious processes. Some alternatives include Nuclear Medicine- and Molecular Imaging-based strategies. However, radiopharmaceuticals that are available for routine assessments are not specific to differentiating infectious from aseptic inflammatory processes. In this context, [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub> was synthesized using an automated module and radiochemical; in vivo and in vitro studies were performed. The radiopharmaceutical remained stable in saline (up to 180 min) and in rodent serum (up to 120 min) with radiochemical purities > 99 and 95%, respectively. Partition coefficient and serum protein binding at 60 min were determined (−3.63 ± 0.17 and 44.06 ± 1.88%, respectively). Ex vivo biodistribution, as well as in vivo microPET/CT images in mice, showed rapid blood clearance with renal excretion and reduced uptake in other organs in <i>Staphylococcus aureus</i>-infected animals. Higher uptake was observed in the target as compared to the non-target tissue (<i>p</i> < 0.0001) at 60 min post administration. The presented in-human clinical case demonstrates uptake of the radiopharmaceutical by <i>Staphyloccocus aureus</i> bacteria. These results indicate the potential of [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub> as a radiopharmaceutical that can be obtained in a hospital radiopharmacy for the diagnosis of infectious processes using PET/CT. |
| first_indexed | 2024-03-08T10:38:17Z |
| format | Article |
| id | doaj.art-4a803869fe9d4bd4998568d88239499b |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-08T10:38:17Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-4a803869fe9d4bd4998568d88239499b2024-01-26T18:05:17ZengMDPI AGPharmaceuticals1424-82472023-12-011714810.3390/ph17010048Radiosynthesis Standardization and Preclinical Assessment of the [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub>: A Translational Study Targeting Differential Diagnosis of Infectious ProcessesAna Cláudia Camargo Miranda0Leonardo Lima Fuscaldi1Jorge Mejia2Fábio Fernando Alves da Silva3Walter Miguel Turato4Fernanda Ferreira Mendonça5Solange Amorim Nogueira6Akemi Osawa7Lilian Yuri Itaya Yamaga8Luciana Malavolta9Marycel Figols de Barboza10Hospital Israelita Albert Einstein, Sao Paulo 05652-900, BrazilDepartment of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo 01224-001, BrazilHospital Israelita Albert Einstein, Sao Paulo 05652-900, BrazilInstituto de Pesquisas Energéticas e Nucleares, Comissão Nacional de Energia Nuclear, Sao Paulo 05508-000, BrazilSchool of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, BrazilDepartment of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo 01224-001, BrazilHospital Israelita Albert Einstein, Sao Paulo 05652-900, BrazilHospital Israelita Albert Einstein, Sao Paulo 05652-900, BrazilHospital Israelita Albert Einstein, Sao Paulo 05652-900, BrazilDepartment of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo 01224-001, BrazilHospital Israelita Albert Einstein, Sao Paulo 05652-900, BrazilHuman bacterial infections significantly contribute to the increase in healthcare-related burdens. This scenario drives the study of novel techniques for the early and precise diagnosis of infectious processes. Some alternatives include Nuclear Medicine- and Molecular Imaging-based strategies. However, radiopharmaceuticals that are available for routine assessments are not specific to differentiating infectious from aseptic inflammatory processes. In this context, [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub> was synthesized using an automated module and radiochemical; in vivo and in vitro studies were performed. The radiopharmaceutical remained stable in saline (up to 180 min) and in rodent serum (up to 120 min) with radiochemical purities > 99 and 95%, respectively. Partition coefficient and serum protein binding at 60 min were determined (−3.63 ± 0.17 and 44.06 ± 1.88%, respectively). Ex vivo biodistribution, as well as in vivo microPET/CT images in mice, showed rapid blood clearance with renal excretion and reduced uptake in other organs in <i>Staphylococcus aureus</i>-infected animals. Higher uptake was observed in the target as compared to the non-target tissue (<i>p</i> < 0.0001) at 60 min post administration. The presented in-human clinical case demonstrates uptake of the radiopharmaceutical by <i>Staphyloccocus aureus</i> bacteria. These results indicate the potential of [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub> as a radiopharmaceutical that can be obtained in a hospital radiopharmacy for the diagnosis of infectious processes using PET/CT.https://www.mdpi.com/1424-8247/17/1/48[<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub>gallium-68automated module synthesisinfectious processesPET/CT imaging |
| spellingShingle | Ana Cláudia Camargo Miranda Leonardo Lima Fuscaldi Jorge Mejia Fábio Fernando Alves da Silva Walter Miguel Turato Fernanda Ferreira Mendonça Solange Amorim Nogueira Akemi Osawa Lilian Yuri Itaya Yamaga Luciana Malavolta Marycel Figols de Barboza Radiosynthesis Standardization and Preclinical Assessment of the [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub>: A Translational Study Targeting Differential Diagnosis of Infectious Processes Pharmaceuticals [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub> gallium-68 automated module synthesis infectious processes PET/CT imaging |
| title | Radiosynthesis Standardization and Preclinical Assessment of the [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub>: A Translational Study Targeting Differential Diagnosis of Infectious Processes |
| title_full | Radiosynthesis Standardization and Preclinical Assessment of the [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub>: A Translational Study Targeting Differential Diagnosis of Infectious Processes |
| title_fullStr | Radiosynthesis Standardization and Preclinical Assessment of the [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub>: A Translational Study Targeting Differential Diagnosis of Infectious Processes |
| title_full_unstemmed | Radiosynthesis Standardization and Preclinical Assessment of the [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub>: A Translational Study Targeting Differential Diagnosis of Infectious Processes |
| title_short | Radiosynthesis Standardization and Preclinical Assessment of the [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub>: A Translational Study Targeting Differential Diagnosis of Infectious Processes |
| title_sort | radiosynthesis standardization and preclinical assessment of the sup 68 sup ga ga dota ubiquicidin sub 29 41 sub a translational study targeting differential diagnosis of infectious processes |
| topic | [<sup>68</sup>Ga]Ga-DOTA-Ubiquicidin<sub>29-41</sub> gallium-68 automated module synthesis infectious processes PET/CT imaging |
| url | https://www.mdpi.com/1424-8247/17/1/48 |
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