Medical Isotopes Research Center, Peking University, Beijing 100191, China.
Mol Pharm. 2012 May 7;9(5):1409-17. doi: 10.1021/mp200661t. Epub 2012 Apr 11.
We recently designed and synthesized a Glu-c(RGDyK)-bombesin (RGD-BBN) heterodimeric peptide exhibiting a dual integrin α(v)β(3) and gastrin-releasing peptide receptor (GRPR) targeting property. In this study, we investigated whether (99m)Tc-labeled RGD-BBN peptide could be used for the noninvasive detection of lung carcinoma by using small-animal single-photon emission computed tomography (SPECT)/CT. RGD-BBN peptide was conjugated with 6-hydrazinonicotinyl (HYNIC) and then radiolabeled with (99m)Tc using tricine and TPPTS as the coligands (TPPTS = trisodium triphenylphosphine-3,3',3"-trisulfonate). The biodistribution, planar gamma imaging, and small-animal SPECT/CT studies of (99m)Tc-HYNIC(tricine)(TPPTS)-RGD-BBN ((99m)Tc-RGD-BBN) were performed in C57/BL6 mice bearing Lewis lung carcinoma (LLC) or bearing both inflammation and LLC. HYNIC-RGD-BBN possessed a dual integrin α(v)β(3) and GRPR binding capacity. (99m)Tc-RGD-BBN was prepared with a high radiochemical purity (>98%), and it exhibited specific tumor imaging with high contrast to the contralateral background. (99m)Tc-RGD-BBN was superior to (18)F-FDG for distinguishing lung carcinoma from inflammation. The uptake of (99m)Tc-RGD-BBN in LLC xenografts was 2.69 ± 0.66% ID/g at 1 h postinjection (p.i.) and was decreased to 1.99 ± 0.61% ID/g at 2 h p.i. The inflammation uptake of (99m)Tc-RGD-BBN was 1.20 ± 0.32% ID/g at 1 h and 0.56 ± 0.17% ID/g at 2 h p.i., respectively. High pancreas uptake (25.76 ± 5.49%ID/g and 19.56 ± 6.78% ID/g at 1 and 2 h p.i., respectively) was also found due to the high GRPR expression of this organ. Small-animal SPECT/CT using (99m)Tc-RGD-BBN can specifically detect the LLC pulmonary metastases. Our results suggested that SPECT/CT with (99m)Tc-RGD-BBN would provide an effective approach for the noninvasive detection of lung cancer.
我们最近设计并合成了一种 Glu-c(RGDyK)-蛙皮素（RGD-BBN）杂二聚体肽，具有双重整合素 α(v)β(3)和胃泌素释放肽受体（GRPR）靶向特性。在这项研究中，我们使用小动物单光子发射计算机断层扫描（SPECT）/CT 研究了（99m）Tc 标记的 RGD-BBN 肽是否可用于非侵入性检测肺癌。RGD-BBN 肽与 6-肼基烟酸（HYNIC）缀合，然后使用 tricine 和 TPPTS 作为共配体（TPPTS = 三[3,3',3''-三膦基]-三钠盐）用（99m）Tc 放射性标记。在携带 Lewis 肺癌（LLC）或同时携带炎症和 LLC 的 C57/BL6 小鼠中进行了（99m）Tc-HYNIC（tricine）（TPPTS）-RGD-BBN（（99m）Tc-RGD-BBN）的生物分布、平面伽马成像和小动物 SPECT/CT 研究。HYNIC-RGD-BBN 具有双重整合素 α(v)β(3)和 GRPR 结合能力。（99m）Tc-RGD-BBN 的制备具有高放射化学纯度（>98%），并表现出与对侧背景相比具有高对比度的特异性肿瘤成像。与（18）F-FDG 相比，（99m）Tc-RGD-BBN 更能区分肺癌与炎症。（99m）Tc-RGD-BBN 在 LLC 异种移植物中的摄取在注射后 1 小时（p.i.）时为 2.69 ± 0.66% ID/g，在 2 小时 p.i.时降至 1.99 ± 0.61% ID/g。（99m）Tc-RGD-BBN 的炎症摄取在 1 小时和 2 小时 p.i.时分别为 1.20 ± 0.32% ID/g 和 0.56 ± 0.17% ID/g。由于该器官中 GRPR 的高表达，还发现了高胰腺摄取（分别为 25.76 ± 5.49%ID/g 和 19.56 ± 6.78% ID/g，在 1 和 2 小时 p.i.时）。使用（99m）Tc-RGD-BBN 的小动物 SPECT/CT 可以特异性检测到 LLC 肺转移。我们的结果表明，使用（99m）Tc-RGD-BBN 的 SPECT/CT 将为非侵入性检测肺癌提供一种有效方法。
