Department of Radiology, University of Missouri, Columbia, Missouri 78229-3900, USA.
Prostate. 2013 Jun;73(8):842-54. doi: 10.1002/pros.22630. Epub 2012 Dec 31.
Development of high affinity and specificity molecular imaging probes that increase accuracy for early detection of lymph node (LN) metastases is important for improving survivorship in prostate cancer. We evaluated the specificity, sensitivity, and accuracy of fluorescence-labeled bombesin (BBN) peptides to detect LN and systematic metastases in orthotopic mouse models bearing gastrin releasing peptide receptor (GRPR)-positive human prostate cancer.
PC-3 cells were orthotopically implanted in severe combined immunedeficient or thymic nude (nu/nu) male mice. Tumor growth was monitored using magnetic resonance imaging. Alexa Fluor 680 conjugated BBN[7-14]NH2 (AF680-BBN) peptides were administered intravenously at 4-7 weeks post-tumor-implantation. Near-infrared fluorescence (NIRF) imaging was performed for up to 6 hr post-injection. The imaging sensitivity and specificity were assessed by co-registration of AF680-BBN NIRF imaging and luciferase bioluminescence imaging of the PC-3/Luc+ orthotopic mouse model.
AF680-BBN showed a high binding affinity and selectivity to GRPR-positive cancer in vitro and in vivo. LN and peritoneal metastases were detected by NIRF imaging, and confirmed by histopathology. Tumor-to-muscle (T/M) ratio was the highest at 2-hr post-injection (4.12 ± 1.77). Blocking experiments, using unlabeled BBN as the inhibiting agent, significantly reduced the T/M ratio (1.64 ± 0.21, P = 0.02). AF680-BBN NIRF imaging had a sensitivity of 89.4%, specificity of 92.9%, and accuracy of 90.2% for the detection of metastases in mice.
[corrected] The studies suggest the potential of use and development of NIR-fluorescent BBN probes as site-directed agents to help improve the current detection and LN staging accuracy in prostate cancer.
开发高亲和力和特异性的分子成像探针，提高对淋巴结（LN）转移的早期检测准确性，对于提高前列腺癌患者的生存率非常重要。我们评估了荧光标记的蛙皮素（BBN）肽检测胃泌素释放肽受体（GRPR）阳性人前列腺癌荷瘤原位小鼠模型中 LN 和系统性转移的特异性、敏感性和准确性。
将 PC-3 细胞原位植入严重联合免疫缺陷或胸腺裸（nu/nu）雄性小鼠中。使用磁共振成像监测肿瘤生长。在肿瘤植入后 4-7 周，静脉内给予 Alexa Fluor 680 偶联的 BBN[7-14]NH2（AF680-BBN）肽。注射后最多进行 6 小时近红外荧光（NIRF）成像。通过共配准 AF680-BBN NIRF 成像和 PC-3/Luc+原位小鼠模型的荧光素酶生物发光成像，评估成像的灵敏度和特异性。
AF680-BBN 在体外和体内均表现出对 GRPR 阳性癌症的高结合亲和力和选择性。NIRF 成像检测到 LN 和腹膜转移，并通过组织病理学证实。注射后 2 小时肿瘤与肌肉（T/M）比值最高（4.12±1.77）。使用未标记的 BBN 作为抑制剂的阻断实验显著降低了 T/M 比值（1.64±0.21，P=0.02）。AF680-BBN NIRF 成像对小鼠转移的检测具有 89.4%的灵敏度、92.9%的特异性和 90.2%的准确性。
研究表明，近红外荧光 BBN 探针作为靶向试剂具有潜在的应用和开发价值，有助于提高当前前列腺癌的检测和 LN 分期准确性。
