Background: 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.
Methods: 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]NH(2) (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.
Results: 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.
Conclusions: 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.
Written by:
Cai QY, Yu P, Besch-Williford C, Smith CJ, Sieckman GL, Hoffman TJ, Ma L. Are you the author?
Department of Radiology, University of Missouri, Columbia, Missouri; International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, Missouri; Harry S. Truman Veterans' Memorial Hospital, Columbia, Missouri.
Reference: Prostate. 2012 Dec 31(Epub ahead of print)
doi: 10.1002/pros.22630
PubMed Abstract
PMID: 23280511
