Phase I trial of technetium [Leu13] bombesin as cancer seeking agent:: Possible scintigraphic guide for surgery?
Phase I trial of technetium [Leu13] bombesin as cancer seeking agent:: Possible scintigraphic guide for surgery?
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DOI：
10.1177/030089160208800332
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发表时间：
2002-05-01
期刊：
影响因子：
1.9
通讯作者：
Delle Fave, G
中科院分区：
文献类型：
--
作者：
De Vincentis, G;Scopinaro, F;Delle Fave, G
目的和背景：蛙皮素样神经肽同时作为神经递质和生长因子发挥作用。几种人类癌症表现出两栖动物铃蟾肽（ABN）的哺乳动物对应物的三种受体的过表达，即胃泌素释放肽（GRP）、神经介肽B（NMB）和可能的另一种肽。ABN又能够在体外与哺乳动物和人类受体结合，因此研究放射性同位素标记的蛙皮素（BN）和BN样肽作为癌症寻找剂是有趣的。方法和研究设计：从[Leu（13）] ABN的氨基酸序列开始，Demokritos研究所合成并用锝标记了一种新的BN样肽，其具有与两栖动物肽相同的生物学特性：仅在该十四肽的N-末端部分进行了改变。在临床前研究中使用Tc-99 m BN获得令人满意的结果后。我们在托木斯克开始了一项包括癌症患者和正常志愿者的第一阶段试验。3例正常志愿者、1例小细胞肺癌患者和1例原发性前列腺癌患者静脉注射185 MBq后进行了研究。对应于0.7微克的Tc-99 m BN。动态图像采集20分钟，然后进行SPET。全身图像采集患者和正常志愿者I和3小时后，Tc-99 mBN采集。对小细胞肺癌患者行~（99）Tc-MIBI放射性核素显像。结果：未观察到相关副作用。两个肿瘤在早期1-2分钟的平面和断层成像图像上都显示良好。全身图像显示肝脏、肾脏和甲状腺中存在放射性。胃和脾从未成像。前列腺癌患者注射后4分钟在膀胱中发现放射性。三小时全身扫描显示十二指肠放射性。在同时进行Tc-99 m mebi放射性造影的患者中，甲状腺对mebi的摄取远高于Tc-99 m BN，而小细胞肺癌对Tc-99 m BN的摄取高于mebi。结论：Tc-99 mBN对BN受体过表达的肿瘤有较好的显像效果。我们的第一个印象是，在未来这种放射性药物可能作为一种癌症寻找剂和。由于其高肿瘤摄取，也可作为放射性同位素引导手术的放射性示踪剂。
Aims and background: Bombesin-like neuropeptides work as neurotransmitters and growth factors at the same time. Several human cancers show overexpression of three receptors for mammalian counterparts of amphibian bombesins (ABNs), ie gastrin-releasing peptide (GRP), neuromedin B (NMB) and possibly another peptide. ABNs in turn are able to bind to mammalian and human receptors in vitro, and it is therefore interesting to study radioisotope-labeled bombesin (BN) and BN-like peptides as cancer seeking agents. Methods and study design: Starting from the amino acid sequence of [Leu(13)] ABN, the Demokritos Institute has synthesized and labeled with technetium a new BN-like peptide that has the same biological characteristics as the amphibian peptide: changes were made only in the N-terminal part of this tetradecapeptide. After having obtained satisfactory results with Tc-99m BN in a preclinical study. we started a phase 1 trial involving cancer patients as well as normal volunteers in Tomsk. Three normal volunteers, one patient with small cell lung cancer and one patient with primary prostate cancer were studied after iv injection of 185 MBq. corresponding to 0.7 micrograms of Tc-99m BN. Dynamic images of the tumors were acquired for 20 mins, followed by SPET. Total body images were acquired in patients and normal volunteers I and 3 h after Tc-99m BN acquisition. In addition, Tc-99m sestamibi scintigraphy was performed in the patient with small cell lung carcinoma. Results: No relevant side effects were observed. Both tumors were well visualized on early 1-2 mins images with planar as well as tomographic imaging. Total body images showed radioactivity in the liver, kidneys and thyroid gland. The stomach and spleen were never imaged. Radioactivity was found in the urinary bladder 4 mins after injection in the patient with prostate cancer. Three-hour total body scans showed radioactivity in the duodenum. In the patient in whom also Tc-99m sestamibi scintigraphy was performed, thyroid uptake was much higher with sestamibi than with Tc-99m BN, whereas the uptake of small cell lung carcinoma was higher with Tc-99m BN than with sestamibi. Conclusions: Tc-99m BN is able to clearly image tumors with BN receptor overexpression. Our first impression is that in the future this radiopharmaceutical may serve as a cancer seeking agent and. due to its high tumoral uptake, also as a radiotracer for radioisotope-guided surgery.