重组α1-微球蛋白（A1M）被提议作为177Lu-奥曲酸治疗神经内分泌肿瘤期间的保护剂，目前该治疗受到骨髓和肾毒性的限制。 177Lu-奥曲酸和 A1M 联合给药可以通过保护健康组织获得更有效的治疗，但 A1M 的辐射防护作用尚不完全清楚。本研究的目的是检查 177Lu-奥曲酸和/或 A1M 给药后早期肾脏和骨髓的蛋白质组学反应。给小鼠注射 177Lu-奥曲酸和/或 A1M，而对照小鼠注射盐水或 A1M 载体溶液。 24小时或7天后对骨髓、肾髓质和肾皮质进行取样。采用串联质谱法分析差异蛋白表达。剂量测定基于肾脏中的 177Lu 活性。 PHLDA3 是肾组织中最重要的辐射响应蛋白。一般来说，辐射相关蛋白的表达在辐射组之间没有观察到统计学上的显着差异。大多数经典途径是在 177Lu-奥曲酸 A1M 组的骨髓中发现的。总而言之，单独暴露于 177Lu-奥曲酯或与 A1M 一起暴露后，出现了组织依赖性蛋白质组学反应。 177Lu-奥曲酸与A1M联合使用并不能抑制暴露后早期辐射诱导的蛋白表达，应进一步研究后期影响。

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.