Kidney Protection with the Radical Scavenger α<sub>1</sub>-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy
α<sub>1</sub>-Microglobulin (A1M) is an antioxidant found in all vertebrates, including humans. It has enzymatic reductase activity and can scavenge radicals and bind free heme groups. Infused recombinant A1M accumulates in the kidneys and has therefore been successful in protecting kidn...
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MDPI AG
2021-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/8/1271 |
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| author | Amanda Kristiansson Anders Örbom Oskar Vilhelmsson Timmermand Jonas Ahlstedt Sven-Erik Strand Bo Åkerström |
| author_facet | Amanda Kristiansson Anders Örbom Oskar Vilhelmsson Timmermand Jonas Ahlstedt Sven-Erik Strand Bo Åkerström |
| author_sort | Amanda Kristiansson |
| collection | DOAJ |
| description | α<sub>1</sub>-Microglobulin (A1M) is an antioxidant found in all vertebrates, including humans. It has enzymatic reductase activity and can scavenge radicals and bind free heme groups. Infused recombinant A1M accumulates in the kidneys and has therefore been successful in protecting kidney injuries in different animal models. In this review, we focus on A1M as a radioprotector of the kidneys during peptide receptor radionuclide/radioligand therapy (PRRT/RLT). Patients with, e.g., neuroendocrine tumors or castration resistant prostate cancer can be treated by administration of radiolabeled small molecules which target and therefore enable the irradiation and killing of cancer cells through specific receptor interaction. The treatment is not curative, and kidney toxicity has been reported as a side effect since the small, radiolabeled substances are retained and excreted through the kidneys. In recent studies, A1M was shown to have radioprotective effects on cell cultures as well as having a similar biodistribution as the somatostatin analogue peptide <sup>177</sup>Lu-DOTATATE after intravenous infusion in mice. Therefore, several animal studies were conducted to investigate the in vivo radioprotective potential of A1M towards kidneys. The results of these studies demonstrated that A1M co-infusion yielded protection against kidney toxicity and improved overall survival in mouse models. Moreover, two different mouse studies reported that A1M did not interfere with tumor treatment itself. Here, we give an overview of radionuclide therapy, the A1M physiology and the results from the radioprotector studies of the protein. |
| first_indexed | 2024-03-10T09:03:14Z |
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| id | doaj.art-57825ea6b2dc45538b608ec63215b0f4 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T09:03:14Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-57825ea6b2dc45538b608ec63215b0f42023-11-22T06:36:41ZengMDPI AGAntioxidants2076-39212021-08-01108127110.3390/antiox10081271Kidney Protection with the Radical Scavenger α<sub>1</sub>-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand TherapyAmanda Kristiansson0Anders Örbom1Oskar Vilhelmsson Timmermand2Jonas Ahlstedt3Sven-Erik Strand4Bo Åkerström5Department of Clinical Sciences Lund, Oncology, Lund University, 221 00 Lund, SwedenDepartment of Clinical Sciences Lund, Oncology, Lund University, 221 00 Lund, SwedenDepartment of Clinical Sciences Lund, Oncology, Lund University, 221 00 Lund, SwedenDepartment of Clinical Sciences Lund, CIPA, Lund University, 221 84 Lund, SwedenDepartment of Clinical Sciences Lund, Oncology, Lund University, 221 00 Lund, SwedenDepartment of Clinical Sciences Lund, Section for Infection Medicine, Lund University, 221 84 Lund, Swedenα<sub>1</sub>-Microglobulin (A1M) is an antioxidant found in all vertebrates, including humans. It has enzymatic reductase activity and can scavenge radicals and bind free heme groups. Infused recombinant A1M accumulates in the kidneys and has therefore been successful in protecting kidney injuries in different animal models. In this review, we focus on A1M as a radioprotector of the kidneys during peptide receptor radionuclide/radioligand therapy (PRRT/RLT). Patients with, e.g., neuroendocrine tumors or castration resistant prostate cancer can be treated by administration of radiolabeled small molecules which target and therefore enable the irradiation and killing of cancer cells through specific receptor interaction. The treatment is not curative, and kidney toxicity has been reported as a side effect since the small, radiolabeled substances are retained and excreted through the kidneys. In recent studies, A1M was shown to have radioprotective effects on cell cultures as well as having a similar biodistribution as the somatostatin analogue peptide <sup>177</sup>Lu-DOTATATE after intravenous infusion in mice. Therefore, several animal studies were conducted to investigate the in vivo radioprotective potential of A1M towards kidneys. The results of these studies demonstrated that A1M co-infusion yielded protection against kidney toxicity and improved overall survival in mouse models. Moreover, two different mouse studies reported that A1M did not interfere with tumor treatment itself. Here, we give an overview of radionuclide therapy, the A1M physiology and the results from the radioprotector studies of the protein.https://www.mdpi.com/2076-3921/10/8/1271A1Mradical scavengerradionuclide therapykidney protectionPSMAdosimetry |
| spellingShingle | Amanda Kristiansson Anders Örbom Oskar Vilhelmsson Timmermand Jonas Ahlstedt Sven-Erik Strand Bo Åkerström Kidney Protection with the Radical Scavenger α<sub>1</sub>-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy Antioxidants A1M radical scavenger radionuclide therapy kidney protection PSMA dosimetry |
| title | Kidney Protection with the Radical Scavenger α<sub>1</sub>-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy |
| title_full | Kidney Protection with the Radical Scavenger α<sub>1</sub>-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy |
| title_fullStr | Kidney Protection with the Radical Scavenger α<sub>1</sub>-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy |
| title_full_unstemmed | Kidney Protection with the Radical Scavenger α<sub>1</sub>-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy |
| title_short | Kidney Protection with the Radical Scavenger α<sub>1</sub>-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy |
| title_sort | kidney protection with the radical scavenger α sub 1 sub microglobulin a1m during peptide receptor radionuclide and radioligand therapy |
| topic | A1M radical scavenger radionuclide therapy kidney protection PSMA dosimetry |
| url | https://www.mdpi.com/2076-3921/10/8/1271 |
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