Liu Guanshu, Banerjee Sangeeta Ray, Yang Xing, Yadav Nirbhay, Lisok Ala, Jablonska Anna, Xu Jiadi, Li Yuguo, Pomper Martin G, van Zijl Peter
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, USA.
F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
Nat Biomed Eng. 2017;1:977-982. doi: 10.1038/s41551-017-0168-8. Epub 2017 Dec 12.
Safe imaging agents able to render the expression and distribution of cancer receptors, enzymes or other biomarkers would facilitate clinical screening of the disease. Here, we show that diamagnetic dextran particles coordinated to a urea-based targeting ligand for prostate-specific membrane antigen (PSMA) enable targeted magnetic resonance imaging (MRI) of the PSMA receptor. In a xenograft model of prostate cancer, micromolar concentrations of the dextran -ligand probe provided sufficient signal to specifically detect PSMA-expressing tumours via chemical exchange saturation transfer MRI. The dextran-based probe could be detected via the contrast originating from dextran hydroxyl protons, thereby avoiding the need of chemical substitution for radioactive or metallic labelling. Because dextrans are currently used clinically, dextran-based contrast agents may help extend receptor-targeted imaging to clinical MRI.
能够呈现癌症受体、酶或其他生物标志物的表达和分布的安全成像剂将有助于该疾病的临床筛查。在此,我们表明,与基于尿素的前列腺特异性膜抗原(PSMA)靶向配体配位的抗磁性葡聚糖颗粒能够实现PSMA受体的靶向磁共振成像(MRI)。在前列腺癌异种移植模型中,微摩尔浓度的葡聚糖-配体探针提供了足够的信号,以通过化学交换饱和转移MRI特异性检测表达PSMA的肿瘤。基于葡聚糖的探针可通过源自葡聚糖羟基质子的对比来检测,从而避免了放射性或金属标记的化学取代需求。由于葡聚糖目前已在临床上使用,基于葡聚糖的造影剂可能有助于将受体靶向成像扩展到临床MRI。