Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Radiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Chem Biol Drug Des. 2018 Jan;91(1):304-313. doi: 10.1111/cbdd.13082. Epub 2017 Sep 12.
It has been shown that more than 75% of ductal pancreatic adenocarcinomas overexpressed neurotensin (NT) receptors. Overexpression of NT receptors has been reported in various human tumor types. Hence, a non-invasive diagnosis and staging method could be very beneficial. In this work, we describe radiolabeling and evaluation of new neurotensin analogues to target neurotensin receptor-positive tumors such as pancreatic carcinoma. Radiolabeling was performed at 95°C for 10 min using Tc in the presence of tricine/EDDA exchange labeling. Radiochemical yield analysis involved ITLC and HPLC methods. A binding assay test was carried out in nine different concentrations of labeled neurotensin analogues in HT-29 cells. Radiopeptide-specific binding and internalization were studied in NT receptors expressing HT-29 cells. Biodistribution studies were performed in tumor-free BALB/c mice and HT-29 xenografted tumor-bearing nude mice. The peptide was efficiently labeled by Tc with high radiochemical yields (>98%). The radioconjugate was thoroughly stable in the solution and human serum even for 24 hr. The radiolabeled peptide showed high affinity (32.66 ± 4.01 nm) and specificity internalization (>%18 after 4 hr) to HT-29 cells. The radiopeptide efficiently showed tumor size and location in tumor-bearing nude mice. In biodistribution, a receptor-specific uptake of radiopeptide was observed in neurotensin receptor-positive organs such as intestine. Uptake in the tumor was 4.59 ± 0.23% ID/g after 2 hr. Owing to excellent stability, high affinity, rapid blood clearance, low accumulation in non-target organs, and high uptake in tumor, the Tc-HYNIC-peptide is a potential agent for targeting of NTR-overexpressing tumor cells in clinical surroundings. When successfully executed in the clinical surrounding, non-invasive imaging of NTR-positive tumors with Tc-labeled new neurotensin analogues could facilitate therapy procedure and monitoring.
已经表明，超过 75%的导管胰腺腺癌过度表达神经降压素（NT）受体。NT 受体的过度表达已在各种人类肿瘤类型中报道。因此，一种非侵入性的诊断和分期方法可能非常有益。在这项工作中，我们描述了新的神经降压素类似物的放射性标记和评估，以针对神经降压素受体阳性肿瘤，如胰腺癌。放射性标记是在 95°C 下进行的，使用 Tc 在 tricine/EDDA 交换标记存在下进行了 10 分钟。放射化学产率分析涉及 ITLC 和 HPLC 方法。在 HT-29 细胞中进行了 9 种不同浓度标记神经降压素类似物的结合测定试验。在表达 NT 受体的 HT-29 细胞中研究了放射性肽的特异性结合和内化。在无肿瘤 BALB/c 小鼠和 HT-29 异种移植肿瘤裸鼠中进行了生物分布研究。该肽通过 Tc 高效标记，放射化学产率高（>98%）。放射性标记物在溶液中和人血清中即使在 24 小时内也非常稳定。放射性标记的肽对 HT-29 细胞表现出高亲和力（32.66±4.01nm）和特异性内化（>%18 在 4 小时后）。放射性肽在荷瘤裸鼠中能够有效地显示肿瘤的大小和位置。在生物分布中，在神经降压素受体阳性器官如肠道中观察到放射性肽的受体特异性摄取。在 2 小时后，肿瘤的摄取为 4.59±0.23% ID/g。由于其优异的稳定性、高亲和力、快速的血液清除率、低的非靶器官积累和高的肿瘤摄取率， Tc-HYNIC-肽是一种用于靶向 NTR 过表达肿瘤细胞的潜在试剂，在临床环境中。当在临床环境中成功执行时，使用 Tc 标记的新型神经降压素类似物对 NTR 阳性肿瘤进行非侵入性成像，可以促进治疗过程和监测。
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