Document Detail


Near-infrared fluorescence imaging of gastrin releasing peptide receptor targeting in prostate cancer lymph node metastases.
MedLine Citation:
PMID:  23280511     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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]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.
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: [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.
Authors:
Quan-Yu Cai; Ping Yu; Cynthia Besch-Williford; Charles J Smith; Gary L Sieckman; Timothy J Hoffman; Lixin Ma
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-12-31
Journal Detail:
Title:  The Prostate     Volume:  73     ISSN:  1097-0045     ISO Abbreviation:  Prostate     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-26     Completed Date:  2013-07-01     Revised Date:  2014-10-15    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  United States    
Other Details:
Languages:  eng     Pagination:  842-54     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bombesin / analogs & derivatives*,  diagnostic use
Cell Line, Tumor
Fluorescent Dyes / diagnostic use*
Histocytochemistry
Humans
Lymph Nodes / metabolism*,  pathology
Male
Mice
Mice, Nude
Mice, SCID
Microscopy, Fluorescence
Peptide Fragments / diagnostic use*
Prostatic Neoplasms / diagnosis,  metabolism*,  pathology
Receptors, Bombesin / metabolism*
Reproducibility of Results
Sensitivity and Specificity
Chemical
Reg. No./Substance:
0/Fluorescent Dyes; 0/Peptide Fragments; 0/Receptors, Bombesin; 0/bombesin (7-14); PX9AZU7QPK/Bombesin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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