Bhatnagar Akrita, Wang Yuchuan, Mease Ronnie C, Gabrielson Matthew, Sysa Polina, Minn Il, Green Gilbert, Simmons Brian, Gabrielson Kathleen, Sarkar Siddik, Fisher Paul B, Pomper Martin G
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Department of Molecular and Comparative Pathobiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Cancer Res. 2014 Oct 15;74(20):5772-81. doi: 10.1158/0008-5472.CAN-14-0018. Epub 2014 Aug 21.
We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through a systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single-photon emission computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for noninvasive clinical imaging. Furthermore, the approach compares favorably with accepted and emerging clinical standards, including PET with [(18)F]fluorodeoxyglucose and [(18)F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer.
我们描述了一种用于检测前列腺癌的新成像方法,该方法可检测局部或已扩散并转移至软组织和骨骼的前列腺癌。该方法依赖于在AEG-1(MTDH)启动子控制下使用成像报告基因,AEG-1启动子仅在恶性细胞中具有选择性活性。通过基于纳米颗粒的成像构建体的全身递送,在前列腺癌的PC3-ML小鼠模型中,可通过生物发光成像和单光子发射计算机断层扫描以高灵敏度识别病变。这种方法适用于检测前列腺癌转移灶,包括目前尚无可靠的非侵入性临床成像剂的骨病变。此外,该方法与公认的和新兴的临床标准相比具有优势,包括使用[(18)F]氟脱氧葡萄糖和[(18)F]氟化钠的PET。我们的结果提供了一种临床前概念验证,为晚期前列腺癌患者的临床评估提供了理论依据。