Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.
Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
Int J Mol Sci. 2024 Jul 8;25(13):7480. doi: 10.3390/ijms25137480.
Recombinant α-microglobulin (A1M) is proposed as a protector during Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 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 Lu-octreotate and/or A1M administration. Mice were injected with 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 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 Lu-octreotate+A1M group. Altogether, a tissue-dependent proteomic response followed exposure to Lu-octreotate alone or together with A1M. Combining Lu-octreotate with A1M did not inhibit the radiation-induced protein expression early after exposure, and late effects should be further studied.
重组α-微球蛋白（A1M）被提议作为神经内分泌肿瘤的 Lu-奥曲肽治疗的保护剂，目前受到骨髓和肾脏毒性的限制。Lu-奥曲肽和 A1M 的联合给药可能通过保护健康组织而导致更有效的治疗，但 A1M 的放射保护作用尚未完全了解。本研究旨在检查 Lu-奥曲肽和/或 A1M 给药后早期肾脏和骨髓的蛋白质组反应。小鼠注射 Lu-奥曲肽和/或 A1M，而对照小鼠接受生理盐水或 A1M 载体溶液。在 24 小时或 7 天后采集骨髓、肾脏髓质和肾脏皮质。使用串联质谱法分析差异蛋白表达。剂量估计基于肾脏中的 Lu 活性。PHLDA3 是肾脏组织中最突出的辐射反应蛋白。一般来说，在照射组之间未观察到与辐射相关的蛋白质表达的统计学显著差异。大多数经典途径是在 Lu-奥曲肽+A1M 组的骨髓中鉴定出来的。总之，单独或联合使用 Lu-奥曲肽后，暴露于 Lu-奥曲肽后会出现组织依赖性蛋白质组反应。Lu-奥曲肽与 A1M 联合使用并不能抑制暴露后早期的辐射诱导蛋白表达，应进一步研究晚期效应。
