Karunanayake E H, Hearse D J, Mellows G
Biochem J. 1974 Sep;142(3):673-83. doi: 10.1042/bj1420673.
[(14)C]Streptozotocin was synthesized specifically labelled at three positions in the molecule. The biological activity of synthetic streptozotocin was characterised by studies in vivo of its diabetogenic activity and its dose-response curves. After this characterization the excretion pattern of all three labelled forms of streptozotocin was studied. With [1-(14)C]streptozotocin and [2'-(14)C]streptozotocin the injected radioactivity was excreted (approx. 70% and 80% respectively) mainly in the urine, the greater part of the excretion occurring in the first 6h period; small amounts (approx. 9% and 8% respectively) were found in the faeces. In contrast, with [3'-methyl-(14)C]streptozotocin a much smaller proportion (approx. 42%) of the injected radioactivity was excreted in the urine, the major proportion appearing in the first 6h, whereas approx. 53% of the injected radioactivity was retained in the carcasses. In whole-body radioautographic studies very rapid renal clearance and hepatic accumulation of the injected radioactivity was observed with all three labelled forms of the drug. There was some evidence for biliary and intestinal excretion. Major differences were apparent in the tissue-distribution studies, with each of the three labelled forms, particularly with [3'-methyl-(14)C]streptozotocin. There was no accumulation of [1-(14)C]streptozotocin in the pancreas for the 6h period after administration. However, with [3'-methyl-(14)C]streptozotocin (and also [2'-(14)C]streptozotocin) there was evidence of some pancreatic accumulation after 2h. The results indicate that streptozotocin is subjected to considerable metabolic transformation and to rapid renal clearance. The implication of these suggestions is evaluated with particular reference to the diabetogenic action of streptozotocin.
[¹⁴C]链脲佐菌素在分子的三个位置进行了特异性标记合成。通过对其致糖尿病活性及其剂量 - 反应曲线的体内研究来表征合成链脲佐菌素的生物学活性。在进行此表征后，研究了链脲佐菌素所有三种标记形式的排泄模式。对于[1-(¹⁴C)]链脲佐菌素和[2'-(¹⁴C)]链脲佐菌素，注入的放射性主要经尿液排泄（分别约为70%和80%），大部分排泄发生在最初的6小时内；在粪便中发现少量（分别约为9%和8%）。相比之下，对于[3'-甲基-(¹⁴C)]链脲佐菌素，注入的放射性中经尿液排泄的比例要小得多（约42%），大部分在最初6小时出现，而约53%的注入放射性保留在尸体中。在全身放射自显影研究中，观察到所有三种标记形式的药物注入放射性都有非常快速的肾脏清除和肝脏蓄积。有一些证据表明存在胆汁和肠道排泄。在组织分布研究中，三种标记形式中的每一种都有明显差异，特别是[3'-甲基-(¹⁴C)]链脲佐菌素。给药后6小时内，[1-(¹⁴C)]链脲佐菌素在胰腺中没有蓄积。然而，对于[3'-甲基-(¹⁴C)]链脲佐菌素（以及[2'-(¹⁴C)]链脲佐菌素），2小时后有胰腺蓄积的证据。结果表明链脲佐菌素会经历相当程度的代谢转化和快速的肾脏清除。特别参考链脲佐菌素的致糖尿病作用对这些发现的意义进行了评估。
