86Y-DOTA0-D-Phe1-Tyr3-octreotide (SMT487) -: a phase 1 clinical study:: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion
86Y-DOTA0-D-Phe1-Tyr3-octreotide (SMT487) -: a phase 1 clinical study:: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion
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DOI：
10.1007/s00259-003-1117-1
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发表时间：
2003-04-01
影响因子：
9.1
通讯作者：
Pauwels, S
中科院分区：
文献类型：
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作者：
Jamar, F;Barone, R;Pauwels, S
在24例生长抑素受体阳性神经内分泌肿瘤患者的I期正电子发射断层扫描（PET）研究中，评价了Y-86- DOTA（0）-D-Phe（1）-Tyr（3）-奥曲肽（Y-86-SMT 487）的药代动力学和剂量学。在交叉随机化环境中评估了氨基酸（AA）联合输注对肾脏和肿瘤摄取的影响。测试了五种方案：无输注，输注120 g混合AA（26.4 g L-赖氨酸+L-精氨酸）4 h，L-赖氨酸（50 g）4 h，240 g混合AA（52.8 g L-赖氨酸+L-精氨酸）10 h和Lys-Arg（各25 g）4 h。在患者内进行比较。在注射Y-86-SMT 487前0.5小时开始AA输注，并在注射后4、24和48小时获得PET扫描。使用MIRD 3方法计算组织吸收剂量。Y-86-SMT 487显示出快速血浆清除和排他肾脏排泄;在肾脏、肿瘤、脾脏中观察到摄取，在较小程度上在肝脏中观察到摄取。AA混合液输注4 h后，与对照组比较，差异有显著性（P
The pharmacokinetics and dosimetry of Y-86- DOTA(0)-D-Phe(1)-Tyr(3)-octreotide (Y-86-SMT487) were evaluated in a phase I positron emission tomography (PET) study of 24 patients with somatostatin receptor-positive neuroendocrine tumours. The effect of amino acid (AA) co-infusion on renal and tumour uptake was assessed in a cross-over randomised setting. Five regimens were tested: no infusion, 4-h infusion of 120 g mixed AA (26.4 g L-lysine + L-arginine), 4 h L-lysine (50 g), 10 h 240 g mixed AA (52.8 g L-lysine + L-arginine) and 4 h Lys-Arg (25 g each). Comparisons were performed on an intra-patient basis. Infusions of AA started 0.5 h prior to injection of Y-86-SMT487 and PET scans were obtained at 4, 24 and 48 h p.i. Absorbed doses to tissues were computed using the MIRD3 method. Y-86-SMT487 displayed rapid plasma clearance and exclusive renal excretion; uptake was noted in kidneys, tumours, spleen and, to a lesser extent, liver. The 4-h mixed AA co-infusion significantly (P