The YSNSG peptide is a synthetic cyclopeptide targeting αvβ3 integrin with antitumor activity. Previous study has determined main pharmacokinetic parameters in plasma and in tissue in healthy animals using microdialysis. First we aim to assess the impact of a 20 mg/kg dosage instead of 10 mg/kg in tumor growth inhibition. Secondly we aim to investigate the YSNSG peptide distribution in two different tumor regions in animals with melanoma. C57BL/6 mice were exposed at Days 8, 10 and 12 after melanoma cells implantation (B16F1) to different dosage of YSNSG peptide or control, respectively (n = 10 per group). Data analysis was performed at D16, 20 and 24 with a Nonlinear Mixed-Effects (NLME) approach. For pharmacokinetic study n = 8 mice (same disease condition) received YSNSG peptide by intravenous after insertion of two microdialysis probes in central peripheral region of tumor, respectively. Plasma and tissue samples were collected during 2 h. A non-compartmental analysis was performed to determine main pharmacokinetic parameters. There was a significant tumor growth inhibition in mice receiving 20 mg/kg vs Control (p < 0.02). Main plasma parameters were half-life elimination 25.8 ± 8.2 min, volume of distribution 11.9 ± 0.4 mL, clearance 19.8 ± 9.4 mL/h and area under the curve 1,173.6 µg.min/mL. Penetration rate of the YSNSG peptide from plasma to tumor tissue were 3.3 ± 2.1% and 3.4 ± 2.7% in central and peripheral, respectively. Contrary to subcutaneous distribution in healthy animals the distribution of the YSNSG peptide into tumoral tissue is low but seems non-heterogeneous between central and peripheral tumor region.

中文翻译：

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使用微透析在小鼠黑色素瘤模型中YSNSG环肽的肿瘤内分布。

YSNSG肽是具有抗肿瘤活性的靶向αvβ3整联蛋白的合成环肽。先前的研究已经通过微透析确定了健康动物血浆和组织中的主要药代动力学参数。首先，我们旨在评估20 mg / kg剂量而不是10 mg / kg剂量对肿瘤生长的抑制作用。其次，我们旨在研究YSNSG肽在黑色素瘤动物体内两个不同肿瘤区域的分布。将C57BL / 6小鼠在黑素瘤细胞植入后第8、10和12天（B16F1）分别暴露于不同剂量的YSNSG肽或对照（每组n = 10）。使用非线性混合效应（NLME）方法在D16、20和24进行数据分析。为了进行药代动力学研究，分别在肿瘤的中心周围区域插入两个微透析探针后，通过静脉内注射n ＝ 8只小鼠（相同疾病状况）接受了YSNSG肽。在2小时内收集血浆和组织样品。进行非房室分析以确定主要药代动力学参数。与对照组相比，接受20 mg / kg的小鼠有明显的肿瘤生长抑制作用（p <0.02）。主要血浆参数为消除半衰期25.8±8.2分钟，分布体积11.9±0.4 mL，清除率19.8±9.4 mL / h和曲线下面积1,173.6 µg.min / mL。YSNSG肽从血浆到肿瘤组织的穿透率在中央和周围分别为3.3±2.1％和3.4±2.7％。