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Kidney protection with the radical scavenger α1-microglobulin (A1m) during peptide receptor radionuclide and radioligand therapy

Kristiansson, Amanda LU ; Örbom, Anders LU ; Timmermand, Oskar Vilhelmsson LU ; Ahlstedt, Jonas LU ; Strand, Sven Erik LU and Åkerström, Bo LU (2021) In Antioxidants 10(8). p.1-18
Abstract

α1-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... (More)

α1-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 peptide177Lu-DOTA-TATE 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
A1M, Dosimetry, Kidney protection, PSMA, Radical scavenger, Radionuclide therapy
in
Antioxidants
volume
10
issue
8
article number
1271
pages
1 - 18
publisher
MDPI AG
external identifiers
  • scopus:85112073751
  • pmid:34439519
ISSN
2076-3921
DOI
10.3390/antiox10081271
language
English
LU publication?
yes
additional info
Funding Information: This work was funded by the Swedish Cancer Society (grant no. 190470Pj), the Swedish Research Council (VR; grant no. 2017-00696), the Swedish Prostate Cancer Federation, Swedish Foundation for Strategic Research (SSF), the Royal Physiographic Society in Lund, and the Clinic of Oncology in Lund?s research foundation. Research grants from Guard Therapeutics International (formerly A1M Pharma AB) and Berta Kamprad?s Foundation (grant no. FBKS-2021-33-(348). Funding Information: Funding: This work was funded by the Swedish Cancer Society (grant no. 190470Pj), the Swedish Research Council (VR; grant no. 2017-00696), the Swedish Prostate Cancer Federation, Swedish Foundation for Strategic Research (SSF), the Royal Physiographic Society in Lund, and the Clinic of Oncology in Lund’s research foundation. Research grants from Guard Therapeutics International (formerly A1M Pharma AB) and Berta Kamprad’s Foundation (grant no. FBKS-2021-33-(348). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
id
05a61049-1946-4edd-8749-cd4032a5d48d
date added to LUP
2021-08-18 11:10:03
date last changed
2024-06-15 14:37:42
@article{05a61049-1946-4edd-8749-cd4032a5d48d,
  abstract     = {{<p>α1-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-DOTA-TATE 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.</p>}},
  author       = {{Kristiansson, Amanda and Örbom, Anders and Timmermand, Oskar Vilhelmsson and Ahlstedt, Jonas and Strand, Sven Erik and Åkerström, Bo}},
  issn         = {{2076-3921}},
  keywords     = {{A1M; Dosimetry; Kidney protection; PSMA; Radical scavenger; Radionuclide therapy}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1--18}},
  publisher    = {{MDPI AG}},
  series       = {{Antioxidants}},
  title        = {{Kidney protection with the radical scavenger α1-microglobulin (A1m) during peptide receptor radionuclide and radioligand therapy}},
  url          = {{http://dx.doi.org/10.3390/antiox10081271}},
  doi          = {{10.3390/antiox10081271}},
  volume       = {{10}},
  year         = {{2021}},
}