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Recombinant alpha(1...
Recombinant alpha(1)-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a Lu-177-DOTATATE Mouse Radiation Model
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- Alattar, Abdul Ghani (author)
- Lund University,Lunds universitet,Stamceller till röda blodkroppar,Forskargrupper vid Lunds universitet,Transfusionsmedicin,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Stem Cells to Red Blood Cells,Lund University Research Groups,Transfusion Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Kristiansson, Amanda (author)
- Lund University,Lunds universitet,Antioxidationsmedicin,Forskargrupper vid Lunds universitet,Neonatologi,Antioxidation medicine,Lund University Research Groups,Neonatology,Skåne University Hospital
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- Karlsson, Helena (author)
- Lund University,Lunds universitet,Neonatologi,Forskargrupper vid Lunds universitet,Neonatology,Lund University Research Groups,Skåne University Hospital
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- Vallius, Suvi (author)
- Lund University,Lunds universitet,Neonatologi,Forskargrupper vid Lunds universitet,Neonatology,Lund University Research Groups,Skåne University Hospital
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- Ahlstedt, Jonas (author)
- Lund University,Lunds universitet,Lund University Bioimaging Center,Medicinska fakulteten,Faculty of Medicine
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- Forssell-Aronsson, Eva, 1961 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för medicinsk strålningsvetenskap,Institute of Clinical Sciences, Department of Medical Radiation Sciences
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- Åkerström, Bo (author)
- Lund University,Lunds universitet,Antioxidationsmedicin,Forskargrupper vid Lunds universitet,Antioxidation medicine,Lund University Research Groups
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- Strand, Sven-Erik (author)
- Lund University,Lunds universitet,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,LU profilområde: Ljus och material,Lunds universitets profilområden,Systemic Radiation Therapy Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,LU Profile Area: Light and Materials,Lund University Profile areas
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- Flygare, Johan (author)
- Lund University,Lunds universitet,Stamceller till röda blodkroppar,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Stem Cells to Red Blood Cells,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Gram, Magnus (author)
- Lund University,Lunds universitet,Neonatologi,Forskargrupper vid Lunds universitet,Sjukdomsorsakande oxidation,Neonatology,Lund University Research Groups,Redox Medicine,Skåne University Hospital
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Biomolecules. - 2218-273X. ; 13:6
- Related links:
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http://dx.doi.org/10... (free)
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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https://lup.lub.lu.s...
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Abstract
Subject headings
Close
- Lu-177-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although Lu-177-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. alpha (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 Lu-177-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-Lu-177-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 Lu-177-DOTATATE, may reduce hematopoietic and kidney toxicity during PRRT with Lu-177-DOTATATE.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- peptide receptor radionuclide therapy
- alpha(1)-microglobulin
- radiation
- oxidative stress
- bone marrow toxicity
- renal damage
- amino acids
- Mice
- Animals
- Octreotide/pharmacology
- Kidney/metabolism
- Disease Models, Animal
- Amino Acids/pharmacology
- Organometallic Compounds/pharmacology
Publication and Content Type
- ref (subject category)
- art (subject category)
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