Muetterties K A, Hoener B A, Engelstad B L, Tongol J M, Wikstrom M G, Wang S C, Eason R G, Moseley M E, White D L
Department of Radiology, School of Medicine, University of California, San Francisco 94143.
Magn Reson Med. 1991 Nov;22(1):88-100. doi: 10.1002/mrm.1910220110.
Succinyl (SDF), phenylsuccinyl (PSDF), glutaryl (GDF), and phenylglutaryl (PGDF) derivatives of desferrioxamine B (DF) have been synthesized. In rats given the 59Fe(III) chelates of each these ligands at tracer levels, 82-94% of the 59Fe was eliminated within 1-2 days. 59Fe given as DF, SDF, and GDF chelates was excreted primarily in the urine, while nearly 50% of that given as PSDF and PGDF was excreted in the feces. Correspondingly, Fe-DF, Fe-SDF, and Fe-GDF (0.2 mmol/kg) produced early, marked renal, but no gastrointestinal magnetic resonance imaging (MRI) enhancement. Fe-PSDF and Fe-PGDF (0.2 mmol/kg) produced marked and rapid MRI enhancement of the upper small intestine. In animals with cannulated bile ducts, 59Fe from 59Fe-PGDF (carrier added, 0.1 mmol/kg) appeared rapidly in the collected bile, but not in the intestinal contents, proving that the contrast agent reaches the bowel via the bile. These changes in the excretion and MRI enhancement patterns brought about by the presence of a phenyl substituent apparently were not related to changes in lipophilicity or protein binding.
已合成去铁胺B（DF）的琥珀酰（SDF）、苯琥珀酰（PSDF）、戊二酰（GDF）和苯戊二酰（PGDF）衍生物。给大鼠注射每种这些配体的示踪水平的59Fe（III）螯合物后，1 - 2天内59Fe的82 - 94%被清除。以DF、SDF和GDF螯合物形式给予的59Fe主要经尿液排泄，而以PSDF和PGDF形式给予的59Fe近50%经粪便排泄。相应地，Fe - DF、Fe - SDF和Fe - GDF（0.2 mmol/kg）早期可使肾脏产生明显的磁共振成像（MRI）增强，但对胃肠道无增强作用。Fe - PSDF和Fe - PGDF（0.2 mmol/kg）可使上小肠产生明显且快速的MRI增强。在胆管插管的动物中，59Fe - PGDF（添加载体，0.1 mmol/kg）中的59Fe迅速出现在收集的胆汁中，但未出现在肠内容物中，证明造影剂经胆汁到达肠道。由苯基取代基的存在所导致的排泄和MRI增强模式的这些变化显然与亲脂性或蛋白质结合的变化无关。
