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標題: 抑制腎臟對放射核種標幟體抑素衍生物的吸收
Inhibition of Renal Uptake of Radiolabelled Somatostatin Analogues
作者: 張偉政
Chang, Wei-Cheng
關鍵字: Somatostatin;體抑素
出版社: 獸醫學系暨研究所
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神經內分泌腫瘤會表現具有高親合性的體抑素接受器,因此能夠利用放射核種標幟體抑素衍生物來進行閃爍造影技術而應用於這類腫瘤的診斷及治療。然而,腎臟會高度吸收放射核種所標幟的物質導致腎臟產生放射性毒性;這是因為經放射核種標幟的胜肽會經由絲球體濾過且有效的被近腎小管上皮細胞藉由飽飲作用攝入細胞內所引起的傷害。本研究我們嘗試利用各種正電胺基酸溶液和其他的物質來評估其抑制腎臟重吸收放射活性的能力及其安全性。方法:公的SD大鼠(200-250克),事先給予阻斷重吸收的處置,再由大鼠尾靜脈給予注射111In-DOTATOC。於注射後24小時,將大鼠犧牲,採取大鼠的數個器官並測量其放射活性。結果:改變尿液的pH值不能降低腎臟對111In-DOTATOC的吸收。而給予lysine (400 mg/kg)能夠產生超過40%抑制腎臟吸收放射活性的效果,但是它可能會造成高血鉀和代謝作用的改變。在合併給予arginine和histidine也能夠產生超過40%的抑制效果而且其造成的副作用較單獨給予lysine小。Maleate (400 mg/kg)是非常有效地能夠抑制超過50%的重吸收作用。另外,我們嘗試於注射111In-DOTATOC的前5小時分別給予colchicines (1 mg/kg)、vincristine (0.1 mg/kg)、noscapine (100 mg/kg)及nocodazole (1 mg/kg),發現能夠有意義的降低腎臟的重吸收(分別能降低31%、26%、41%及46%)。此外,合併給予正電胺基酸、ATP阻斷劑及Microtubule抑制劑的灌流有顯著抑制腎臟吸收放射活性的效果。結論:這些物質的給予能有效地降低腎臟的放射活性,以致於能夠給予較高劑量的放射核種標幟體抑素的衍生物,來進行閃爍造影的檢查及胜肽接受器放射核種的治療。

Neuroendocine tumors express high affinity somatostatin receptors that enable scintigraphic imaging using radiolabelled somatostatin analogues for application of tumors diagnosis and therapy. However, the high renal uptake of the radiolabelled compounds may lead to renal radiation toxicity, because of the radiolabelled peptides are filtered by the glomerulus and effectively taken up in proximal tubule cells by endocytosis. The aim of this study was to investigate of various basic amino acid solutions and other compounds in order to assess their safety and their capacity to inhibit the renal uptake of 111In-DOTATOC. Male Spraque-Dawley rats (200-250 g), in the presence of reuptake blocker, were injected with 111In-DOTATOC. At 24 hours after injection, rats were sacrificed and organs were isolated and counted for radioactivity. Our data show that changing the pH value of the urine did not reduced kidney uptake of 111In-DOTATOC. Lysine (400 mg/kg) were resulted in more than 40% inhibition of kidney uptake, but it may induce hyperkalacmia and metabolic changes. Combination of arginine and histidine were also resulted more than 40% inhibition, nevertheless it have less side effect than lysine. Maleate (400 mg/kg) were more effective to reduce renal uptake about over 50%. Further, coinjection of colchicines (1 mg/kg), vincristine (0.1 mg/kg), noscapine (100 mg/kg), nocodazole (1 mg/kg) 5 hours before injection of 111In-DOTATOC were significantly reduced kidney uptake (respective inhibitions of 31%, 26%, 41% and 46%). Besides, there is a notable inhibition of renal uptake by combining basic amino acids, ATP blockers, and microtubule inhibitors. Administration of these compounds effectively reduce kidney radioactivity in order to allow the administration of higher doses of radiolabelled somatostatin analogues for scintigraphy and peptide receptor radionuclide therapy.
其他識別: U0005-2901200705031500
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