van Eerd Julliëtte E M, Vegt Erik, Wetzels Jack F M, Russel Frans G M, Masereeuw Rosalinde, Corstens Frans H M, Oyen Wim J G, Boerman Otto C
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Nucl Med. 2006 Mar;47(3):528-33.
111In-Diethylenetriaminepentaacetic acid-octreotide generally is used for the scintigraphic imaging of neuroendocrine and other somatostatin receptor-positive tumors. On the basis of the successful targeting of octreotide, radiolabeled somatostatin analogs, such as 90Y-(1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid [DOTA])0-Tyr3-octreotide and 177Lu-DOTA0-Tyr3-octreotate, were developed for peptide receptor radionuclide therapy. However, the maximum tolerated doses of these analogs are limited because of the high and persistent renal uptake that leads to relatively high radiation doses in the kidneys. Renal uptake can be reduced by coinfusion of basic amino acids or polypeptides. However, high doses of basic amino acids can induce severe side effects. It was reported that the infusion of gelatin-based plasma expanders resulted in increased low-molecular-weight proteinuria, suggesting that these plasma expanders interfere with the tubular reabsorption of peptides and proteins. In the present study, we analyzed the effects of several plasma expanders on the renal uptake of 111In-octreotide in rats and mice.
Wistar rats and BALB/c mice were injected with 0.5 or 0.1 mL of plasma expander, respectively. Thereafter, the animals received 111In-octreotide intravenously. Animals were killed at 20 h after the injection of the radiopharmaceutical. Organs were dissected, and the amount of radioactivity in the organs and tissues was measured.
The administration of 20 mg of Gelofusine in rats or 4 mg in mice was as effective in reducing the renal uptake of 111In-octreotide as the administration of 80 or 20 mg of lysine in rats or mice, respectively, without reducing 111In-octreotide uptake in receptor-positive organs. Plasma expanders based on starch or dextran had no effect on the renal uptake of 111In-octreotide.
The gelatin-based plasma expander Gelofusine significantly reduced the kidney uptake of 111In-octreotide as effectively as did lysine. Because Gelofusine is a well-known and generally used blood volume substitute that can be applied safely without the induction of toxicity, evaluation of this compound for its potential to reduce the kidney uptake of radiolabeled peptides in patients is warranted.
铟-111 二乙烯三胺五乙酸-奥曲肽一般用于神经内分泌肿瘤及其他生长抑素受体阳性肿瘤的闪烁显像。基于奥曲肽的成功靶向作用，开发了放射性标记的生长抑素类似物，如钇-90（1,4,7,10-四氮杂环十二烷-N,N',N'',N'''-四乙酸[DOTA]）0-酪氨酰3-奥曲肽和镥-177 DOTA0-酪氨酰3-奥曲肽，用于肽受体放射性核素治疗。然而，这些类似物的最大耐受剂量有限，因为肾脏对其摄取高且持续，导致肾脏接受相对较高的辐射剂量。通过同时输注碱性氨基酸或多肽可减少肾脏摄取。然而，高剂量的碱性氨基酸可诱发严重副作用。据报道，输注明胶基血浆扩容剂会导致低分子量蛋白尿增加，提示这些血浆扩容剂会干扰肽和蛋白质的肾小管重吸收。在本研究中，我们分析了几种血浆扩容剂对大鼠和小鼠肾脏摄取铟-111 奥曲肽的影响。
分别给Wistar大鼠和BALB/c小鼠注射0.5或0.1 mL血浆扩容剂。此后，动物静脉注射铟-111 奥曲肽。在注射放射性药物后20小时处死动物。解剖器官，测量器官和组织中的放射性活度。
给大鼠注射20 mg血定安或给小鼠注射4 mg血定安，在减少铟-111 奥曲肽肾脏摄取方面，分别与给大鼠或小鼠注射80或20 mg赖氨酸的效果相同，且不降低受体阳性器官对铟-111 奥曲肽的摄取。基于淀粉或右旋糖酐的血浆扩容剂对铟-111 奥曲肽的肾脏摄取无影响。
明胶基血浆扩容剂血定安显著降低铟-111 奥曲肽的肾脏摄取，效果与赖氨酸相同。由于血定安是一种知名且常用的血容量替代品，可安全应用且不诱发毒性，因此有必要评估该化合物在降低患者体内放射性标记肽肾脏摄取方面的潜力。
