Effects of Recombinant α 1 -Microglobulin on Early Proteomic Response in Risk Organs after Exposure to 177 Lu-Octreotate.

Recombinant α ₁ -microglobulin (A1M) is proposed as a protector during ¹⁷⁷ Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of ¹⁷⁷ 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 ¹⁷⁷ Lu-octreotate and/or A1M administration. Mice were injected with ¹⁷⁷ 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 ¹⁷⁷ 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 ¹⁷⁷ Lu-octreotate+A1M group. Altogether, a tissue-dependent proteomic response followed exposure to ¹⁷⁷ Lu-octreotate alone or together with A1M. Combining ¹⁷⁷ Lu-octreotate with A1M did not inhibit the radiation-induced protein expression early after exposure, and late effects should be further studied.