Place D A, Faustino P J, Berghmans K K, van Zijl P C, Chesnick A S, Cohen J S
Department of Pharmacology, Georgetown University Medical Center, Rockville, MD 20850.
Magn Reson Imaging. 1992;10(6):919-28. doi: 10.1016/0730-725x(92)90446-7.
Previously we reported that Mn(III)tetra(4-sulfonatophenyl) porphyrin, MnTPPS4, is a contrast agent which can effectively enhance tumor detection by MRI. By imaging 30 additional athymic nude mice bearing subcutaneous MCF-7 WT human breast carcinoma xenografts, we have extended dose-contrast relationships over a wide range of intraperitoneal (IP) doses ranging from 0.025 to 0.50 mmol/kg. The benefits of IP injection are higher possible doses on a volume basis and a reduction in toxicity versus IV administration. Full coronal cross-section images have been obtained on a 2-T spectrometer. Although individual tumor masses displayed different distribution patterns, reflective of their internal morphology, single doses of 0.10 mmol/kg or greater were necessary to produce a detectable effect. At a dose of 0.50 mmol/kg, marked enhancement was produced. Multiple small dosages administered over the course of several days before imaging did not produce increased enhancement. Preliminary results on the new porphyrin derivative, MnTPPS3, indicate that the ratio of the toxic dose to the effective dose may be adjustable to render this class of agents clinically useful.
此前我们报道过，锰（III）四（4-磺酸苯基）卟啉（MnTPPS4）是一种造影剂，可有效增强MRI对肿瘤的检测效果。通过对另外30只荷人MCF-7 WT皮下乳腺癌异种移植瘤的无胸腺裸鼠进行成像，我们扩展了剂量-对比关系，腹腔内（IP）剂量范围从0.025至0.50 mmol/kg。与静脉注射相比，IP注射的好处在于以体积计可能有更高的剂量，且毒性降低。已在一台2-T光谱仪上获得了完整的冠状截面图像。尽管单个肿瘤块呈现出不同的分布模式，反映了它们的内部形态，但要产生可检测到的效果，单次剂量需达到0.10 mmol/kg或更高。在0.50 mmol/kg的剂量下，产生了明显的增强效果。在成像前数天内多次给予小剂量并未产生增强效果的增加。新卟啉衍生物MnTPPS3的初步结果表明，毒性剂量与有效剂量之比可能是可调节的，以使这类药物具有临床实用性。
