In vivo selection of phage for the optical imaging of PC-3 human prostate carcinoma in mice.
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 approximately 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.
Newton
Jessica R
JR
Department of Biochemistry, University of Missouri, Columbia, MO 65212, USA.
Kelly
Kimberly A
KA
Mahmood
Umar
U
Weissleder
Ralph
R
Deutscher
Susan L
SL
D000818:Animals; D001435:Bacteriophages / Q000235:genetics*; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*