Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Charlotte Ytterbrink
,
Emman Shubbar
,
Toshima Z Parris
ORCID logo ,
Britta Langen
,
Malin Druid
,
Emil Schüler
,
Sven Erik Strand
ORCID logo ,
Bo Åkerström
,
Magnus Gram
ORCID logo ,
Khalil Helou
ORCID logo ,
Eva Forssell-Aronsson
* ORCID logo
Version 1 : Received: 10 March 2024 / Approved: 11 March 2024 / Online: 11 March 2024 (21:46:26 CET)

How to cite: Ytterbrink, C.; Shubbar, E.; Parris, T.Z.; Langen, B.; Druid, M.; Schüler, E.; Strand, S.E.; Åkerström, B.; Gram, M.; Helou, K.; Forssell-Aronsson, E. Effects of Recombinant α1-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to 177Lu-Octreotate. Preprints 2024, 2024030610. https://doi.org/10.20944/preprints202403.0610.v1 Ytterbrink, C.; Shubbar, E.; Parris, T.Z.; Langen, B.; Druid, M.; Schüler, E.; Strand, S.E.; Åkerström, B.; Gram, M.; Helou, K.; Forssell-Aronsson, E. Effects of Recombinant α1-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to 177Lu-Octreotate. Preprints 2024, 2024030610. https://doi.org/10.20944/preprints202403.0610.v1

Abstract

Recombinant α1-microglobulin (A1M) is proposed as 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 radioprotecting 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 hours or 7 days. Differential protein expression was analyzed with tandem mass spectrometry. Dosimetric estimation was based on 177Lu activity in kidney. PHLDA3 was the most prominent radiation responsive protein in kidney tissue. In general, no statistically significant difference in 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, 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.

Keywords

A1M; antioxidant; proteomics; radio-protector; kidney; bone marrow; PRRT

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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