Synthesis and Evaluation of Gd(III) -Based Magnetic Resonance Contrast Agents for Molecular Imaging of Prostate-Specific Membrane Antigen.
Synthesis and Evaluation of Gd(III) -Based Magnetic Resonance Contrast Agents for Molecular Imaging of Prostate-Specific Membrane Antigen.
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DOI：
10.1002/anie.201503417
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发表时间：
2015-09-07
期刊：
影响因子：
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通讯作者：
Pomper MG
中科院分区：
文献类型：
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作者：
Banerjee SR;Ngen EJ;Rotz MW;Kakkad S;Lisok A;Pracitto R;Pullambhatla M;Chen Z;Shah T;Artemov D;Meade TJ;Bhujwalla ZM;Pomper MG
磁共振（MR）成像是有利的，因为它同时提供解剖，功能和分子信息。MR分子成像可以将这种已建立的临床模式的高空间分辨率与体内分子谱分析结合联合收割机。然而，由于MR成像固有的低灵敏度，需要生物靶的高局部浓度来产生可辨别的MR对比度。我们假设前列腺特异性膜抗原（PSMA），一个有吸引力的前列腺癌的成像和治疗的目标，可以作为一个合适的生物标志物的MR为基础的分子成像。我们已经合成了三种新的高亲和力，低分子量的钆III为基础的PSMA靶向造影剂，每个分子含有一到三个钆III螯合物。我们评估了这些药物在溶液中、前列腺癌细胞中和体内实验模型中的弛豫特性，以证明基于PSMA的MR分子成像的可行性。
Magnetic resonance (MR) imaging is advantageous because it concurrently provides anatomic, functional, and molecular information. MR molecular imaging can combine the high spatial resolution of this established clinical modality with molecular profiling in vivo. However, as a result of the intrinsically low sensitivity of MR imaging, high local concentrations of biological targets are required to generate discernable MR contrast. We hypothesize that the prostate-specific membrane antigen (PSMA), an attractive target for imaging and therapy of prostate cancer, could serve as a suitable biomarker for MR-based molecular imaging. We have synthesized three new high-affinity, low-molecular-weight GdIII-based PSMA-targeted contrast agents containing one to three GdIII chelates per molecule. We evaluated the relaxometric properties of these agents in solution, in prostate cancer cells, and in an in vivo experimental model to demonstrate the feasibility of PSMA-based MR molecular imaging.