PDF(Pubmed)
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 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.
摘要：
建议将重组α1-微球蛋白（A1M）作为神经内分泌肿瘤177Lu-奥曲酯治疗期间的保护剂，目前受到骨髓和肾毒性的限制。177Lu-奥曲酯和A1M的共同给药可以通过保护健康组织而导致更有效的治疗，但A1M的辐射防护作用尚不完全清楚。这项研究的目的是检查177Lu-奥曲酯和/或A1M给药后早期肾脏和骨髓的蛋白质组学反应。小鼠注射177Lu-奥曲酯和/或A1M，而对照小鼠接受盐水或A1M载体溶液。骨髓,肾髓质,24h或7d后采样肾皮质。用串联质谱法分析差异蛋白表达。剂量学估计基于肾脏中的177Lu活性。PHLDA3是肾组织中最突出的辐射响应蛋白。总的来说,照射组之间辐射相关蛋白表达无统计学差异.在177Lu-奥曲酯A1M组的骨髓中鉴定出大多数经典途径。总之,单独或与A1M一起暴露于177Lu-奥曲酯后，出现组织依赖性蛋白质组学反应。177Lu-奥曲酯与A1M联合使用不会抑制暴露后早期辐射诱导的蛋白表达，后期效应有待进一步研究。
