Rampy M A, Brown R S, Pinchuk A N, Weichert J P, Skinner R W, Fisher S J, Wahl R L, Gross M D, Ethier S P, Counsell R E
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA.
J Nucl Med. 1996 Sep;37(9):1540-5.
Iodine-125-12-[m-iodophenyl]-dodecylphosphocholine (NM-324) has been shown to accumulate in a variety of animal tumor models. Moreover, preliminary pharmacokinetic studies with NM-324 are being conducted in cancer patients. The present study was undertaken to examine the potential application of NM-324 as a breast tumor-imaging agent.
Two animal models of breast cancer were utilized: namely, syngenic inbred Lewis female rats bearing the rat mammary tumor (RMT) and athymic mice with HT-39 human tumor xenografts. After i.v. administration of NM-324, the tissue distribution of radioactivity was determined at various time points. Gamma camera scintigrams were also acquired to confirm the biodistribution results. Macro- and microautoradiography were used to analyze cellular distribution of radioactivity in tumors.
In the rat mammary tumor model, levels of radioactivity in the tumor reached a maximum at 24 hr after i.v. administration (1.65% ID/g, tumor-to-blood 6.4). These tumors could be visualized by gamma camera scintigraphy as early as 1 hour after administration. In the nude mouse model, levels of radioactivity in tumor reached a maximum at 48 hr after i.v. administration (4.96 %ID/g, tumor-to-blood 5.5). Tissues expected to interfere with the resolution of breast lesions such as fat, heart, lung and muscle displayed much lower concentrations of the radioactivity. Gamma camera scintigraphy confirmed the results observed from biodistribution experiments. Lipid extraction of the tumors and major organs in both animal models showed the sole presence of unchanged NM-324. Microautoradiographic analysis of slices of rat mammary and HT-39 tumors provided additional information regarding the intratumoral distribution of radioactivity.
The ability of radioiodinated phospholipid analogs to accumulate in breast tumors reinforces the need for further investigation of this type of radiopharmaceutical as tumor imaging agents.
碘-125-12-[间碘苯基]-十二烷基磷酰胆碱（NM-324）已被证明可在多种动物肿瘤模型中蓄积。此外，正在癌症患者中进行NM-324的初步药代动力学研究。本研究旨在考察NM-324作为乳腺肿瘤显像剂的潜在应用。
使用两种乳腺癌动物模型：即携带大鼠乳腺肿瘤（RMT）的同基因近交系Lewis雌性大鼠和带有HT-39人肿瘤异种移植物的无胸腺小鼠。静脉注射NM-324后，在不同时间点测定放射性的组织分布。还采集了γ相机闪烁扫描图以确认生物分布结果。宏观和微观放射自显影用于分析肿瘤中放射性的细胞分布。
在大鼠乳腺肿瘤模型中，静脉注射后24小时肿瘤中的放射性水平达到最高（1.65%注射剂量/克，肿瘤与血液比值为6.4）。给药后1小时即可通过γ相机闪烁扫描观察到这些肿瘤。在裸鼠模型中，静脉注射后48小时肿瘤中的放射性水平达到最高（4.96%注射剂量/克，肿瘤与血液比值为5.5）。预期会干扰乳腺病变分辨的组织如脂肪、心脏、肺和肌肉中放射性浓度低得多。γ相机闪烁扫描证实了生物分布实验的结果。两种动物模型中肿瘤和主要器官的脂质提取显示仅存在未变化的NM-324。大鼠乳腺和HT-39肿瘤切片的微观放射自显影分析提供了有关肿瘤内放射性分布的更多信息。
放射性碘化磷脂类似物在乳腺肿瘤中蓄积的能力进一步表明需要对这类放射性药物作为肿瘤显像剂进行进一步研究。
