Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546.
Nucl Med Biol. 2011 Oct;38(7):1043-52. doi: 10.1016/j.nucmedbio.2011.03.005. Epub 2011 Aug 9.
Hepatocellular carcinoma is the most common form of primary hepatic carcinoma. A new N(2)S(2) tetradentate ligand, N-[2-(triphenylmethyl)thioethyl]-3-aza-19-ethyloxycarbonyl-3-[2-(triphenylmethyl)thioethyl]octadecanoate (H(3)MN-16ET), was introduced and labeled with (188)Re to create (188)Re-MN-16ET in the Lipiodol phase. The potential of (188)Re-MN-16ET/Lipiodol for hepatoma therapy was evaluated in a hepatocellular carcinoma animal model of Sprague-Dawley rats implanted with the N1S1 cell line.
Synthesis of H(3)MN-16ET was described, and characterization was identified by infrared, nuclear magnetic resonance and mass spectra. We compared the effects of transchelating agents (glucoheptonate or tartaric acid) and a reducing agent (stannous chloride) on the complexing of (188)Re-perrhenate and H(3)MN-16ET. Twenty-four rats implanted with hepatoma were injected with 3.7 MBq/0.1 ml of (188)Re-MN-16ET/Lipiodol or (188)Re-MN-16ET via transcatheter arterial embolization. Biodistribution experiments and single-photon emission computed tomography imaging were performed to investigate tumor accumulation.
H(3)MN-16ET was proved to easily conjugate with the Re isotope and showed good solubility in Lipiodol. The radiochemical purity of (188)Re-MN-16ET/Lipiodol with 10 mg tartaric acid and stannous chloride was shown to be more than 90%. The major distribution sites of (188)Re-MN-16ET in Sprague-Dawley rats were hepatoma and the liver. However, the radioactivity at the tumor site postadministered with (188)Re-MN-16ET was quickly decreased from 9.15±0.23 (at 1 h) to 2.71%±0.18% of injected dose/g (at 48 h). The biodistribution and micro-single-photon emission computed tomography/computed tomography image data showed that (188)Re-MN-16ET/Lipiodol was selectively retained at the tumor site, with 11.55±1.44, 13.16±1.46 and 10.67%±0.95% of injected dose/g at 1, 24 and 48 h postinjection, respectively. The radioactivity in normal liver tissue was high but significantly lower than that of the tumors.
H(3)MN-16ET is a suitable tetradentate ligand for (188)Re labeling. From the animal data, we suggest that (188)Re-MN-16ET/Lipiodol has the potential to be a therapeutic radiopharmaceutical for hepatoma treatment.
肝细胞癌是原发性肝癌最常见的形式。一种新的 N(2)S(2)四齿配体，N-[2-(三苯甲基)硫代乙基]-3-氮杂-19-乙氧基羰基-3-[2-(三苯甲基)硫代乙基]十八烷酸酯（H(3)MN-16ET），被引入并与 (188)Re 标记，以在 Lipiodol 相中创建 (188)Re-MN-16ET。在 Sprague-Dawley 大鼠荷瘤模型中，我们评估了 (188)Re-MN-16ET/Lipiodol 用于肝癌治疗的潜力，该模型植入了 N1S1 细胞系。
描述了 H(3)MN-16ET 的合成，并通过红外、核磁共振和质谱鉴定了其特征。我们比较了转金属试剂（葡庚糖酸盐或酒石酸）和还原剂（氯化亚锡）对 (188)Re-perrhenate 和 H(3)MN-16ET 络合的影响。24 只荷瘤大鼠通过经导管动脉栓塞术注射 3.7 MBq/0.1 ml 的 (188)Re-MN-16ET/Lipiodol 或 (188)Re-MN-16ET。进行生物分布实验和单光子发射计算机断层扫描成像以研究肿瘤积聚。
H(3)MN-16ET 被证明易于与 Re 同位素结合，并在 Lipiodol 中表现出良好的溶解性。用 10 mg 酒石酸和氯化亚锡制备的 (188)Re-MN-16ET/Lipiodol 的放射化学纯度大于 90%。(188)Re-MN-16ET 在 Sprague-Dawley 大鼠中的主要分布部位是肝癌和肝脏。然而，给予 (188)Re-MN-16ET 后，肿瘤部位的放射性活性很快从 1 h 的 9.15±0.23%降至 48 h 的 2.71%±0.18%。生物分布和微单光子发射计算机断层扫描/计算机断层扫描图像数据表明，(188)Re-MN-16ET/Lipiodol 选择性地保留在肿瘤部位，1、24 和 48 h 时的注射剂量/g 分别为 11.55±1.44%、13.16±1.46%和 10.67%±0.95%。正常肝组织中的放射性活性较高，但明显低于肿瘤。
H(3)MN-16ET 是 (188)Re 标记的合适四齿配体。从动物数据来看，我们认为 (188)Re-MN-16ET/Lipiodol 有可能成为治疗肝癌的治疗性放射性药物。
