Chong Hyun-Soon, Garmestani Kayhan, Bryant L Henry, Milenic Diane E, Overstreet Terrish, Birch Noah, Le Thien, Brady Erik D, Brechbiel Martin W
Biological, Chemical, and Physical Sciences Department, Chemistry Division, Illinois Institute of Technology, Chicago, Illinois 60616, USA.
J Med Chem. 2006 Mar 23;49(6):2055-62. doi: 10.1021/jm051009k.
Novel chelates PIP-DTPA, AZEP-DTPA, NETA, NPTA, and PIP-DOTA were synthesized and evaluated as potential magnetic resonance imaging (MRI) contrast enhancement agents. The T1 and T2 relaxivities of their corresponding Gd(III) complexes are reported. At clinically relevant field strengths, the relaxivities of the complexes are comparable to that of the clinically used contrast agents Gd(DTPA) and Gd(DOTA). The serum stability of the 153Gd-labeled complexes, Gd(PIP-DTPA), Gd(AZEP-DTPA), Gd(PIP-DOTA), Gd(NETA), and Gd(NPTA), was assessed by measuring the release of 153Gd from the complexes. 153Gd(NETA), 153Gd(PIP-DTPA), and 153Gd(PIP-DOTA) were found to be stable in human serum for up to 14 days without any measurable loss of radioactivity. Significant release of 153Gd was observed with the 153Gd(III) radiolabled NPTA. In vivo biodistribution of the153Gd-labeled complexes was performed to evaluate their in vivo stability. While Gd(AZEP-DTPA) and Gd(NPTA) were found to be unstable in vivo, Gd(NETA), Gd(PIP-DTPA), and Gd(PIP-DOTA) were excreted without dissociation. These results suggest that the Gd(III) complexes of the novel chelates NETA, PIP-DTPA, and PIP-DOTA possess potential as MRI contrast enhancement agents. In particular, the piperidine backboned chelates Gd(PIP-DTPA) and Gd(PIP-DOTA) displayed reduced kidney retention as compared to the nonspecific MRI contrast agent Gd(DOTA) at all time points, although the observed effects were relatively small at 0.5 h postinjection. Incorporation of the lipophilic piperidine ring appears to confer a moderate effect on the liver uptake of these two chelates.
合成了新型螯合物PIP-DTPA、AZEP-DTPA、NETA、NPTA和PIP-DOTA，并将其作为潜在的磁共振成像（MRI）造影增强剂进行评估。报告了它们相应的Gd（III）配合物的T1和T2弛豫率。在临床相关场强下，这些配合物的弛豫率与临床使用的造影剂Gd（DTPA）和Gd（DOTA）相当。通过测量153Gd从配合物中的释放，评估了153Gd标记的配合物Gd（PIP-DTPA）、Gd（AZEP-DTPA）、Gd（PIP-DOTA）、Gd（NETA）和Gd（NPTA）的血清稳定性。发现153Gd（NETA）、153Gd（PIP-DTPA）和153Gd（PIP-DOTA）在人血清中稳定长达14天，且没有任何可测量的放射性损失。观察到153Gd（III）放射性标记的NPTA有明显的153Gd释放。进行了153Gd标记配合物的体内生物分布研究，以评估它们的体内稳定性。虽然发现Gd（AZEP-DTPA）和Gd（NPTA）在体内不稳定，但Gd（NETA）、Gd（PIP-DTPA）和Gd（PIP-DOTA）在不解离的情况下被排泄。这些结果表明，新型螯合物NETA、PIP-DTPA和PIP-DOTA的Gd（III）配合物具有作为MRI造影增强剂的潜力。特别是，与非特异性MRI造影剂Gd（DOTA）相比，含哌啶主链的螯合物Gd（PIP-DTPA）和Gd（PIP-DOTA）在所有时间点的肾脏滞留都有所降低，尽管在注射后0.5小时观察到的效果相对较小。亲脂性哌啶环的引入似乎对这两种螯合物的肝脏摄取有适度影响。
