Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Recombinant α 1-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a 177Lu-DOTATATE Mouse Radiation Model.

Alattar, Abdul Ghani LU orcid ; Kristiansson, Amanda LU ; Karlsson, Helena LU ; Vallius, Suvi LU ; Ahlstedt, Jonas LU ; Forssell-Aronsson, Eva ; Åkerström, Bo LU ; Strand, Sven-Erik LU ; Flygare, Johan LU and Gram, Magnus LU orcid (2023) In Biomolecules 13(6). p.1-13
Abstract

177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although 177Lu-DOTATATE is mostly well tolerated in patients, bone marrow suppression and long-term renal toxicity are still side effects that should be considered. Amino acids are often used to minimize renal radiotoxicity, however, they are associated with nausea and vomiting in patients. α 1-microglobulin (A1M) is an antioxidant with heme- and radical-scavenging abilities. A recombinant form (rA1M) has previously been shown to be renoprotective in preclinical models, including in PRRT-induced kidney damage. Here, we further investigated rA1M's renal protective effect in a mouse ... (More)

177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although 177Lu-DOTATATE is mostly well tolerated in patients, bone marrow suppression and long-term renal toxicity are still side effects that should be considered. Amino acids are often used to minimize renal radiotoxicity, however, they are associated with nausea and vomiting in patients. α 1-microglobulin (A1M) is an antioxidant with heme- and radical-scavenging abilities. A recombinant form (rA1M) has previously been shown to be renoprotective in preclinical models, including in PRRT-induced kidney damage. Here, we further investigated rA1M's renal protective effect in a mouse 177Lu-DOTATATE model in terms of administration route and dosing regimen and as a combined therapy with amino acids (Vamin). Moreover, we investigated the protective effect of rA1M on peripheral blood and bone marrow cells, as well as circulatory biomarkers. Intravenous (i.v.) administration of rA1M reduced albuminuria levels and circulatory levels of the oxidative stress-related protein fibroblast growth factor-21 (FGF-21). Dual injections of rA1M (i.e., at 0 and 24 h post- 177Lu-DOTATATE administration) preserved bone marrow cellularity and peripheral blood reticulocytes. Administration of Vamin, alone or in combination with rA1M, did not show any protection of bone marrow cellularity or peripheral reticulocytes. In conclusion, this study suggests that rA1M, administered i.v. for two consecutive days in conjunction with 177Lu-DOTATATE, may reduce hematopoietic and kidney toxicity during PRRT with 177Lu-DOTATATE.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Mice, Animals, Octreotide/pharmacology, Kidney/metabolism, Disease Models, Animal, Amino Acids/pharmacology, Organometallic Compounds/pharmacology
in
Biomolecules
volume
13
issue
6
article number
923
pages
1 - 13
publisher
MDPI AG
external identifiers
  • scopus:85163618104
  • pmid:37371508
ISSN
2218-273X
DOI
10.3390/biom13060928
language
English
LU publication?
yes
id
6f80ffad-fdfe-44fb-90b2-ea53b30c17af
date added to LUP
2023-09-01 08:35:19
date last changed
2024-04-20 02:22:15
@article{6f80ffad-fdfe-44fb-90b2-ea53b30c17af,
  abstract     = {{<p> 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although  177Lu-DOTATATE is mostly well tolerated in patients, bone marrow suppression and long-term renal toxicity are still side effects that should be considered. Amino acids are often used to minimize renal radiotoxicity, however, they are associated with nausea and vomiting in patients. α  1-microglobulin (A1M) is an antioxidant with heme- and radical-scavenging abilities. A recombinant form (rA1M) has previously been shown to be renoprotective in preclinical models, including in PRRT-induced kidney damage. Here, we further investigated rA1M's renal protective effect in a mouse  177Lu-DOTATATE model in terms of administration route and dosing regimen and as a combined therapy with amino acids (Vamin). Moreover, we investigated the protective effect of rA1M on peripheral blood and bone marrow cells, as well as circulatory biomarkers. Intravenous (i.v.) administration of rA1M reduced albuminuria levels and circulatory levels of the oxidative stress-related protein fibroblast growth factor-21 (FGF-21). Dual injections of rA1M (i.e., at 0 and 24 h post- 177Lu-DOTATATE administration) preserved bone marrow cellularity and peripheral blood reticulocytes. Administration of Vamin, alone or in combination with rA1M, did not show any protection of bone marrow cellularity or peripheral reticulocytes. In conclusion, this study suggests that rA1M, administered i.v. for two consecutive days in conjunction with  177Lu-DOTATATE, may reduce hematopoietic and kidney toxicity during PRRT with  177Lu-DOTATATE. </p>}},
  author       = {{Alattar, Abdul Ghani and Kristiansson, Amanda and Karlsson, Helena and Vallius, Suvi and Ahlstedt, Jonas and Forssell-Aronsson, Eva and Åkerström, Bo and Strand, Sven-Erik and Flygare, Johan and Gram, Magnus}},
  issn         = {{2218-273X}},
  keywords     = {{Mice; Animals; Octreotide/pharmacology; Kidney/metabolism; Disease Models, Animal; Amino Acids/pharmacology; Organometallic Compounds/pharmacology}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{1--13}},
  publisher    = {{MDPI AG}},
  series       = {{Biomolecules}},
  title        = {{Recombinant α 
        1-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a 
        177Lu-DOTATATE Mouse Radiation Model.}},
  url          = {{http://dx.doi.org/10.3390/biom13060928}},
  doi          = {{10.3390/biom13060928}},
  volume       = {{13}},
  year         = {{2023}},
}