Decristoforo Clemens, Maina Theodosia, Nock Berthold, Gabriel Michael, Cordopatis Paul, Moncayo Roy
Univ.-Klinik fuer Nuklearmedizin, Anichstrasse 35, 6020 Innsbruck, Austria,
Eur J Nucl Med Mol Imaging. 2003 Sep;30(9):1211-9. doi: 10.1007/s00259-003-1225-y. Epub 2003 Jul 4.
Somatostatin receptor (SSTR) scintigraphy with indium-111 DTPA-octreotide has become a routine diagnostic procedure in oncology. However, it suffers some drawbacks concerning the limited availability, suboptimal imaging properties and elevated radiation burden of (111)In. We have recently been involved in the development of a new tetraamine-functionalised [Tyr(3)]octreotate derivative (Demotate 1) that can be easily labelled with technetium-99m at high specific activities. (99m)Tc-Demotate 1 showed promising properties in preclinical studies. In this study we report on the first experience with (99m)Tc-Demotate 1 in patients. Six patients (mean age 56 years) with carcinoid tumours ( n=2) or endocrine pancreatic tumours ( n=4) with previously positive SSTR scintigraphy were enrolled in the study. Patients were injected with 500-600 MBq (99m)Tc-Demotate 1. Clinical and laboratory parameters were controlled up to 3 months p.i. Blood samples were taken at various time points up to 24 h p.i., and urine was collected up to 24 h. Whole-body images were acquired at 15-30 min, 1-2 h, 4 h and 24 h p.i. with additional single-photon emission tomography imaging at 1-4 h. Blood excretion was very rapid, with <2%ID in plasma after 1 h, and urinary excretion <20% ID after 6 h. Two patients complained of mild gastrointestinal problems and paraesthesia, but no other adverse reactions were observed. SSTR-positive tumours were rapidly visualised as early as 15 min p.i., with maximum tumour uptake (up to 19% ID) and tumour/organ ratios as early as 1 h p.i. Organs of predominant physiological uptake were the spleen and the kidneys, with no intestinal excretion detectable up to 24 h. (99m)Tc-Demotate 1 detected 11 lesions while In-Oct detected ten; differences in uptake behaviour were observed in three patients. This study shows for the first time that peptides derivatised with a tetraamine ligand for labelling with (99m)Tc show suitable properties for receptor imaging in patients. (99m)Tc-Demotate 1 is a promising agent for the visualisation of SSTR-positive lesions in patients, allowing rapid imaging as early as 1 h p.i.; some differences are observed in pharmacokinetic behaviour compared with (111)In-DTPA-octreotide.
使用铟 - 111 DTPA - 奥曲肽进行的生长抑素受体（SSTR）闪烁扫描已成为肿瘤学中的常规诊断程序。然而，它存在一些缺点，包括可用性有限、成像特性欠佳以及铟 - 111的辐射负担较高。我们最近参与了一种新型四胺功能化的[酪氨酸（3）]奥曲肽衍生物（去甲奥曲肽1）的研发，该衍生物可以很容易地用高比活度的锝 - 99m进行标记。锝 - 99m - 去甲奥曲肽1在临床前研究中显示出有前景的特性。在本研究中，我们报告了锝 - 99m - 去甲奥曲肽1在患者中的首次应用经验。6例患者（平均年龄56岁），其中类癌肿瘤患者2例，内分泌胰腺肿瘤患者4例，这些患者之前的SSTR闪烁扫描结果为阳性，被纳入本研究。患者注射了500 - 600 MBq的锝 - 99m - 去甲奥曲肽1。在注射后长达3个月的时间内对临床和实验室参数进行监测。在注射后长达24小时的不同时间点采集血样，并收集尿液直至24小时。在注射后15 - 30分钟、1 - 2小时、4小时和24小时采集全身图像，并在1 - 4小时进行额外的单光子发射断层扫描成像。血液排泄非常迅速，1小时后血浆中放射性小于注入剂量的2%，6小时后尿液排泄小于注入剂量的20%。两名患者抱怨有轻微的胃肠道问题和感觉异常，但未观察到其他不良反应。SSTR阳性肿瘤早在注射后15分钟即可快速显影，注射后1小时即可达到最大肿瘤摄取（高达注入剂量的19%）以及肿瘤/器官比值。主要生理性摄取的器官是脾脏和肾脏，直至24小时均未检测到肠道排泄。锝 - 99m - 去甲奥曲肽1检测到11个病灶，而铟 - 奥曲肽检测到10个；在3例患者中观察到摄取行为的差异。本研究首次表明，用四胺配体衍生化以用于锝 - 99m标记的肽在患者受体成像中显示出合适的特性。锝 - 99m - 去甲奥曲肽1是一种有前景的用于患者SSTR阳性病灶可视化的药物，早在注射后1小时即可进行快速成像；与铟 - 111 DTPA - 奥曲肽相比，在药代动力学行为上观察到一些差异。
