Buchegger Franz, Bonvin Florent, Kosinski Marek, Schaffland Andreas O, Prior John, Reubi Jean C, Bläuenstein Peter, Tourwé Dirk, García Garayoa Elisa, Bischof Delaloye Angelika
Division of Nuclear Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
J Nucl Med. 2003 Oct;44(10):1649-54.
The study aim was to assess the safety, biodistribution, tissue kinetics, and tumor uptake of the (99m)Tc-labeled neurotensin (NT) analog NT-XI.
Four patients presenting ductal pancreatic adenocarcinoma were studied with (99m)Tc-NT-XI. Patients were followed by scintigraphy up to 4 h and by continued blood and urinary sampling until surgery 18-22 h after injection. Surgical tissue samples were analyzed for radioactivity uptake and NT receptor expression.
No side effects were observed on injection of (99m)Tc-NT-XI. Blood biologic half-lives alpha and beta were 35 min (range, 17-62 min) and 230 min (range, 107-383 min), respectively. Repeated whole-body scintigraphy performed in 2 patients showed a single exponential decrease of whole-body activity with half-lives of 101 and 232 min. Tracer elimination was mainly renal, with 92% and 98% of activity counted in urine in the first 20 h. Kidney, liver, spleen, and bone marrow activity uptake was observed in all patients. Tumor was not visualized in the first 3 patients but could be localized by tomoscintigraphy in the pancreas head region of patient 4. In vitro tissue analysis showed high expression of NT receptor in the tumor of patient 4, correlated with the highest tumor radioactivity uptake and the highest tumor-to-fat radioactivity ratio. In vitro receptor expression was also positive in a second patient having a tumor characterized by very low cellularity; however, the remaining 2 tumors lacked NT receptor expression.
Injection of (99m)Tc-NT-XI was well tolerated. The in vivo tumor uptake appeared specific as it was observed in the 1 patient with a pancreatic tumor that expressed high amounts of NT receptor. The results are compatible with preclinical animal results and in favor of further development of radiolabeled NT analogs for diagnosis or therapy of cancer.
本研究旨在评估（99m）Tc标记的神经降压素（NT）类似物NT-XI的安全性、生物分布、组织动力学和肿瘤摄取情况。
对4例胰腺导管腺癌患者进行了（99m）Tc-NT-XI研究。对患者进行长达4小时的闪烁扫描，并持续采集血液和尿液样本直至注射后18 - 22小时手术。对手术组织样本进行放射性摄取和NT受体表达分析。
注射（99m）Tc-NT-XI未观察到副作用。血液生物学半衰期α和β分别为35分钟（范围17 - 62分钟）和230分钟（范围107 - 383分钟）。对2例患者进行的重复全身闪烁扫描显示全身活性呈单指数下降，半衰期分别为101分钟和232分钟。示踪剂主要通过肾脏消除，前20小时尿液中活性计数分别为92%和98%。所有患者均观察到肾脏、肝脏、脾脏和骨髓有活性摄取。前3例患者的肿瘤未显影，但在患者4的胰头区域通过断层闪烁扫描可定位肿瘤。体外组织分析显示患者4的肿瘤中NT受体高表达，与最高的肿瘤放射性摄取和最高的肿瘤与脂肪放射性比值相关。在另一例肿瘤细胞含量极低的患者中，体外受体表达也呈阳性；然而，其余2例肿瘤缺乏NT受体表达。
注射（99m）Tc-NT-XI耐受性良好。体内肿瘤摄取似乎具有特异性，因为在1例表达大量NT受体的胰腺肿瘤患者中观察到了这种摄取。这些结果与临床前动物实验结果相符，有利于进一步开发用于癌症诊断或治疗的放射性标记NT类似物。
