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体内 [68Ga]-DOTATOC 与神经内分泌肿瘤中生长抑素受体的结合——肽质量的影响。

In vivo binding of [68Ga]-DOTATOC to somatostatin receptors in neuroendocrine tumours--impact of peptide mass.

机构信息

Department of Biochemistry and Organic Chemistry, BMC, Uppsala University, Uppsala, Sweden.

出版信息

Nucl Med Biol. 2010 Apr;37(3):265-75. doi: 10.1016/j.nucmedbio.2009.11.008. Epub 2010 Jan 15.

Abstract

OBJECTIVES

The aim of this pilot study was to explore the impact of peptide mass on binding of [(68)Ga]-DOTATOC to neuroendocrine tumour somatostatin receptors in vivo using a tracer of variable specific radioactivity (SRA) and to show the logistic feasibility of sequential PET scans in the same patient.

MATERIAL AND METHODS

Nine patients with gastroenteropancreatic neuroendocrine tumours were included. Six of them underwent three sequential PET-CT examinations with intravenous injections of [(68)Ga]-DOTATOC proceeded by 0, 50 and 250 or 500 microg of octreotide, administered 10 min before the tracer. Three patients were examined by dynamic and static PET/CT for pharmacokinetic and dosimetric calculations. The [(68)Ga]-DOTATOC synthesis included preconcentration and purification of the generator eluate and microwave heating in a semi-automated in-house procedure.

RESULTS

[(68)Ga]-DOTATOC synthesis and quality control were accomplished within 30 min and radiochemical purity was >95%. The tracer accumulation in the tumours varied and depended on the total amount of the administered peptide. In five of six patients, the highest tumour-to-normal tissue ratio was found when 50 microg of octreotide was preadministered. One patient showed a continuously increasing tumour uptake. Dosimetrically, a large variation in organ doses was found (kidney: 0.086-0.168 mSv/MBq; liver: 0.026-0.096 mSv/MBq; spleen: 0.046-0.226 mSv/MBq). The effective dose (0.015, 0.0067 and 0.0042 mSv/MBq) was correlated to the total amount of decays.

DISCUSSION

Three sequential PET-CT examinations using (68)Ga-based tracer was carried out in 1 day. The use of high SRA [(68)Ga]-DOTATOC and unlabelled octreotide indicates an optimal mass leading to better image contrast. [(68)Ga]-DOTATOC-PET-CT employing variable SRA may be utilised for accurate quantification of tumour uptake with subsequent dosimetry for personalized therapy management.

摘要

目的

本初步研究旨在探讨使用不同比活度(SRA)示踪剂研究肽质量对体内 [(68)Ga]-DOTATOC 与神经内分泌肿瘤生长抑素受体结合的影响,并展示同一患者连续 PET 扫描的逻辑可行性。

材料与方法

纳入 9 例胃肠胰神经内分泌肿瘤患者。其中 6 例患者行 3 次连续的 [(68)Ga]-DOTATOC 静脉注射,分别在示踪剂注射前 10min 给予 0、50 和 250 或 500μg 奥曲肽。另外 3 例患者进行了动态和静态 PET/CT 检查,以进行药代动力学和剂量学计算。[(68)Ga]-DOTATOC 的合成包括发生器洗脱液的预浓缩和纯化,以及在半自动化的内部程序中进行微波加热。

结果

[(68)Ga]-DOTATOC 的合成和质量控制在 30min 内完成,放射化学纯度>95%。肿瘤的示踪剂积聚是变化的,并且取决于所给予的肽的总量。在 6 例患者中的 5 例中,当预先给予 50μg 奥曲肽时,肿瘤与正常组织的比值最高。1 例患者表现出持续增加的肿瘤摄取。在剂量学方面,器官剂量变化很大(肾脏:0.086-0.168mSv/MBq;肝脏:0.026-0.096mSv/MBq;脾脏:0.046-0.226mSv/MBq)。有效剂量(0.015、0.0067 和 0.0042mSv/MBq)与总衰变数相关。

讨论

在 1 天内进行了 3 次基于 [(68)Ga]的示踪剂连续 PET-CT 检查。使用高 SRA [(68)Ga]-DOTATOC 和未标记的奥曲肽表明,最佳质量可以带来更好的图像对比度。采用可变 SRA 的 [(68)Ga]-DOTATOC-PET-CT 可用于准确量化肿瘤摄取,并进行随后的剂量学,以实现个体化治疗管理。

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