Plotzke K P, Rampy M A, Meyer K, Ruyan M, Fisher S J, Wahl R L, Skinner R W, Gross M D, Counsell R E
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0626.
J Nucl Biol Med (1991). 1993 Dec;37(4):264-72.
The phospholipid ether analog, [125I]-1-O-[12-(m-iodophenyl)dodecyl]propanediol-3-phosphocholine (NM-295) was synthesized and evaluated for its ability to visualize tumors. Preliminary studies were performed in rats bearing the Walker 256 carcinosarcoma. Most of the radioactivity was cleared from the animals during the first 24 hours. However, the tumor showed a decreased rate of clearance of radioactivity when compared with non-target tissue. This difference in the clearance rate allowed for excellent images of the tumor at 24 hours. Scintigraphic images compared favorably with other radioiodinated phospholipid ether analogs such as [125I-rac-1-O-[12-(m-iodophenyl)dodecyl]-2-O-methylglycero-3- phosphocholine (NM-294) and [125I]-12-(m-iodophenyl)dodecyl phosphocholine (NM-324). In contrast with the latter two compounds, however, tissue distribution studies revealed that NM-295 cleared at a much faster rate from all tissues, including tumor. In addition, within 24 hours following administration of NM-295, over 70% of the radioactivity was excreted as compared to 50% and 20% for NM-294 and NM-324, respectively. The majority of excreted radioactivity appeared in the urine for all three compounds. Thin-layer chromatography of urine and fecal extracts showed the presence of metabolites only. In contrast, lipid extracts of either liver or tumor demonstrated only the presence of the parent compound. Therefore, these data suggest that in each case it was the parent phospholipid analog that was taken up and retained by the tissues, while the metabolic product(s) was cleared and excreted from the animal.
合成了磷脂醚类似物[125I]-1-O-[12-(间碘苯基)十二烷基]丙二醇-3-磷酸胆碱（NM-295），并对其使肿瘤显影的能力进行了评估。在携带Walker 256癌肉瘤的大鼠身上进行了初步研究。在最初的24小时内，大部分放射性物质从动物体内清除。然而，与非靶组织相比，肿瘤显示出放射性物质清除率降低。这种清除率的差异使得在24小时时能获得肿瘤的清晰图像。闪烁扫描图像与其他放射性碘化磷脂醚类似物如[125I-消旋-1-O-[12-(间碘苯基)十二烷基]-2-O-甲基甘油-3-磷酸胆碱（NM-294）和[125I]-12-(间碘苯基)十二烷基磷酸胆碱（NM-324）相比具有优势。然而，与后两种化合物不同的是，组织分布研究表明NM-295从所有组织（包括肿瘤）中清除的速度要快得多。此外，在给予NM-295后的24小时内，超过70%的放射性物质被排泄，而NM-294和NM-324分别为50%和20%。所有三种化合物排泄出的放射性物质大部分出现在尿液中。尿液和粪便提取物的薄层色谱显示仅存在代谢产物。相比之下，肝脏或肿瘤的脂质提取物仅显示存在母体化合物。因此，这些数据表明，在每种情况下，被组织摄取并保留的是母体磷脂类似物，而代谢产物则从动物体内清除并排泄。
