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Effects of Recombinant α1-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to 177Lu-Octreotate

Ytterbrink, Charlotte ; Shubbar, Emman ; Parris, Toshima Z. ; Langen, Britta ; Druid, Malin ; Schüler, Emil ; Strand, Sven Erik LU ; Åkerström, Bo LU ; Gram, Magnus LU orcid and Helou, Khalil , et al. (2024) In International Journal of Molecular Sciences 25(13).
Abstract

Recombinant α1-microglobulin (A1M) is proposed as a protector during 177Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but the radioprotective action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after 177Lu-octreotate and/or A1M administration. Mice were injected with 177Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24... (More)

Recombinant α1-microglobulin (A1M) is proposed as a protector during 177Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but the radioprotective action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after 177Lu-octreotate and/or A1M administration. Mice were injected with 177Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24 h or 7 d. The differential protein expression was analyzed with tandem mass spectrometry. The dosimetric estimation was based on 177Lu activity in the kidney. PHLDA3 was the most prominent radiation-responsive protein in kidney tissue. In general, no statistically significant difference in the expression of radiation-related proteins was observed between the irradiated groups. Most canonical pathways were identified in bone marrow from the 177Lu-octreotate+A1M group. Altogether, a tissue-dependent proteomic response followed exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not inhibit the radiation-induced protein expression early after exposure, and late effects should be further studied.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
A1M, antioxidant, bone marrow, kidney, proteomics, PRRT, radio-protector
in
International Journal of Molecular Sciences
volume
25
issue
13
article number
7480
publisher
MDPI AG
external identifiers
  • scopus:85198395153
  • pmid:39000587
ISSN
1661-6596
DOI
10.3390/ijms25137480
language
English
LU publication?
yes
id
9b8e4827-495f-427c-b94f-aa1239f4cf28
date added to LUP
2024-09-30 13:56:26
date last changed
2024-10-02 08:40:56
@article{9b8e4827-495f-427c-b94f-aa1239f4cf28,
  abstract     = {{<p>Recombinant α<sub>1</sub>-microglobulin (A1M) is proposed as a protector during <sup>177</sup>Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of <sup>177</sup>Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but the radioprotective action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after <sup>177</sup>Lu-octreotate and/or A1M administration. Mice were injected with <sup>177</sup>Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24 h or 7 d. The differential protein expression was analyzed with tandem mass spectrometry. The dosimetric estimation was based on <sup>177</sup>Lu activity in the kidney. PHLDA3 was the most prominent radiation-responsive protein in kidney tissue. In general, no statistically significant difference in the expression of radiation-related proteins was observed between the irradiated groups. Most canonical pathways were identified in bone marrow from the <sup>177</sup>Lu-octreotate+A1M group. Altogether, a tissue-dependent proteomic response followed exposure to <sup>177</sup>Lu-octreotate alone or together with A1M. Combining <sup>177</sup>Lu-octreotate with A1M did not inhibit the radiation-induced protein expression early after exposure, and late effects should be further studied.</p>}},
  author       = {{Ytterbrink, Charlotte and Shubbar, Emman and Parris, Toshima Z. and Langen, Britta and Druid, Malin and Schüler, Emil and Strand, Sven Erik and Åkerström, Bo and Gram, Magnus and Helou, Khalil and Forssell-Aronsson, Eva}},
  issn         = {{1661-6596}},
  keywords     = {{A1M; antioxidant; bone marrow; kidney; proteomics; PRRT; radio-protector}},
  language     = {{eng}},
  number       = {{13}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Effects of Recombinant α<sub>1</sub>-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to <sup>177</sup>Lu-Octreotate}},
  url          = {{http://dx.doi.org/10.3390/ijms25137480}},
  doi          = {{10.3390/ijms25137480}},
  volume       = {{25}},
  year         = {{2024}},
}