Vegt Erik, Wetzels Jack F M, Russel Frans G M, Masereeuw Rosalinde, Boerman Otto C, van Eerd Juliette E, Corstens Frans H M, Oyen Wim J G
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Nucl Med. 2006 Mar;47(3):432-6.
Peptide receptor-mediated radiotherapy of neuroendocrine and other somatostatin receptor-positive tumors with radiolabeled somatostatin analogs has been applied in several experimental settings. The kidneys are the organs responsible for dose-limiting toxicity attributable to the retention of radiolabeled octreotide in the renal cortex, leading to a relatively high radiation dose that may result in irreversible loss of kidney function. The administration of basic amino acids reduces renal uptake but does have significant side effects. We observed that gelatin-based plasma expanders induced tubular low-molecular-weight proteinuria in healthy volunteers, suggesting that components in these solutions can interfere with the tubular reabsorption of proteins and peptides. Here, we studied the effects of infusion of low doses of the plasma expander succinylated gelatin (GELO) on the renal uptake of 111In-labeled octreotide (111In-OCT).
Five healthy volunteers were given 111In-OCT, first in combination with normal saline and 2 wk later in combination with GELO. Scintigraphic images of the kidneys as well as blood and urine samples were analyzed. To exclude a nonspecific hemodynamic effect of the plasma expander, the procedure was repeated with 5 other volunteers who received the carbohydrate-based plasma expander hydroxyethyl starch (HES).
Low doses of GELO were able to effectively reduce the kidney retention of 111In-OCT. The renal radiation dose was significantly reduced by 45% +/- 10% (mean +/- SD) (P = 0.006), whereas HES showed no significant effect (0% +/- 12%). The infusion of GELO did not cause any side effects.
GELO effectively reduces the renal uptake of 111In-OCT. In contrast to currently used mixtures of amino acids, GELO does not cause any side effects.
用放射性标记的生长抑素类似物进行肽受体介导的神经内分泌及其他生长抑素受体阳性肿瘤的放射治疗已应用于多种实验环境。肾脏是因放射性标记的奥曲肽在肾皮质潴留而导致剂量限制毒性的器官，这会导致相对较高的辐射剂量，可能导致肾功能不可逆转的丧失。碱性氨基酸的给药可减少肾脏摄取，但确实有明显的副作用。我们观察到基于明胶的血浆扩容剂在健康志愿者中诱导肾小管低分子量蛋白尿，提示这些溶液中的成分可干扰蛋白质和肽的肾小管重吸收。在此，我们研究了低剂量血浆扩容剂琥珀酰明胶（GELO）输注对111In标记的奥曲肽（111In - OCT）肾脏摄取的影响。
5名健康志愿者先接受111In - OCT与生理盐水联合给药，2周后接受111In - OCT与GELO联合给药。对肾脏的闪烁图像以及血液和尿液样本进行分析。为排除血浆扩容剂的非特异性血流动力学效应，对另外5名接受基于碳水化合物的血浆扩容剂羟乙基淀粉（HES）的志愿者重复该过程。
低剂量的GELO能够有效降低111In - OCT在肾脏的潴留。肾脏辐射剂量显著降低45%±10%（均值±标准差）（P = 0.006），而HES无显著影响（0%±12%）。GELO输注未引起任何副作用。
GELO有效降低111In - OCT的肾脏摄取。与目前使用的氨基酸混合物不同，GELO不会引起任何副作用。
