Journal
NEOPLASIA
Volume 8, Issue 9, Pages 772-780Publisher
ELSEVIER SCIENCE INC
DOI: 10.1593/neo.06331
Keywords
phage display; optical imaging; drug development; near-infrared (NIR); tumor-imaging agents
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Funding
- NCI NIH HHS [R24 CA92782, P50 CA103130, R24 CA092782, P50 CA103130-01, P50 CA86355, P50 CA086355] Funding Source: Medline
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There is an increasing medical need to detect and spatially localize early and aggressive forms of prostate cancer. Affinity ligands derived from bacteriophage (phage) library screens can be developed to molecularly target prostate cancer with fluorochromes for optical imaging. Toward this goal, we used in vivo phage display and a newly described micropanning assay to select for phage that extravasate and bind human PC-3 prostate carcinoma xenografts in severe combined immune deficiency mice. One resulting phage clone (G1) displaying the peptide sequence IAGLATPGWSHWLAL was fluorescently labeled with the near-infrared fluorophore AlexaFluor 680 and was evaluated both in vitro and in vivo for its ability to bind and target PC-3 prostate carcinomas. The fluorescently labeled phage clone (G1) had a tumor-to-muscle ratio of similar to 30 in experiments. In addition, prostate tumors (PC-3) were readily detectable by optical-imaging methods. These results show proof of principle that disease-specific library-derived fluorescent probes can be rapidly developed for use in the early detection of cancers by optical means.
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