Departments of Chemistry, Molecular Biosciences, Neurobiology and Radiology, Northwestern University, 2145 N. Sheridan Road, Evanston, Illinois 60208, United States.
Inorg Chem. 2024 May 27;63(21):9877-9887. doi: 10.1021/acs.inorgchem.4c00652. Epub 2024 May 15.
F parashift probes with paramagnetically shifted reporter nuclei provide attractive platforms to develop molecular imaging probes. These probes enable ratiometric detection of molecular disease markers using a direct detection technique. Here, we describe a series of trivalent lanthanide (Ln(III)) complexes that are structural analogues of the clinically approved MR contrast agent (CA) ProHance to obtain F parashift probes. We evaluated trans-gadolinium paramagnetic lanthanides compared to diamagnetic for F chemical shift and relaxation rate enhancement. The paramagnetic contribution to chemical shift (δ) for paramagnetic exhibited either shifts to lower frequency (δ < 0 for , , and ) or shifts to higher frequency (δ > 0 for , , and ) compared to F spectroscopic signal. Zero-echo time pulse sequences achieved 56-fold sensitivity enhancement for over , while developing probe-specific pulse sequences with fast delay times and acquisition times achieved 0.6-fold enhancement in limit of detection for . provides an attractive platform to develop F parashift probes for ratiometric detection of enzymatic activity.
具有顺磁位移报告核的 F -parashift 探针为开发分子成像探针提供了有吸引力的平台。这些探针能够使用直接检测技术对分子疾病标志物进行比率检测。在这里，我们描述了一系列三价镧系元素 (Ln(III)) 配合物，它们是临床批准的磁共振对比剂 (CA) ProHance 的结构类似物，以获得 F-parashift 探针。我们评估了顺磁的过渡镓顺磁镧系元素与抗磁的相比，在 F 化学位移和弛豫率增强方面。与 F 光谱信号相比，顺磁 的化学位移 (δ) 表现出较低的频率位移 (δ < 0，对于 、 和 ）或较高的频率位移 (δ > 0，对于 、 和 ）。对于 ，零回波时间脉冲序列实现了 56 倍的灵敏度增强，而开发具有快速延迟时间和采集时间的探针特异性脉冲序列，可将检测限提高 0.6 倍。 为比率检测酶活性提供了开发 F-parashift 探针的有吸引力的平台。
