Abstract | INTRODUCTION: Two-step and three-step pretargeting systems utilizing biotinylated prostate tumor-homing bacteriophage (phage) and (111)In-radiolabeled streptavidin or biotin were developed for use in cancer radioimaging. The in vivo selected prostate carcinoma-specific phage (G1) displaying up to five copies of the peptide IAGLATPGWSHWLAL was the focus of the present study. METHODS: The ability of G1 phage to extravasate and target prostate tumor cells was investigated using immunohistochemistry. G1 phages were biotinylated, streptavidin was conjugated to diethylenetriaminepentaacetic acid ( DTPA) and biotin was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid ( DOTA). Biodistribution studies and single-photon emission computed tomography (SPECT)/CT imaging of xenografted PC-3 tumors via two-step pretargeted (111)In-labeled streptavidin and three-step pretargeted (111)In-labeled biotin were performed in SCID mice to determine the optimal pretargeting method. RESULTS: The ability of G1 phage to extravasate the vasculature and bind directly to human PC-3 prostate carcinoma tumor cells in vivo was demonstrated via immunocytochemical analysis. Comparative biodistribution studies of the two-step and three-step pretargeting strategies indicated increased PC-3 human prostate carcinoma tumor uptake in SCID mice of 4.34+/-0.26 %ID g(-1) at 0.5 h postinjection of (111)In-radiolabeled biotin (utilized in a three-step protocol) compared to 0.67+/-0.06 %ID g(-1) at 24 h postinjection of (111)In radiolabeled streptavidin (employed in a two-step protocol). In vivo SPECT/CT imaging of xenografted PC-3 tumors in SCID mice with the three-step pretargeting method was superior to that of the two-step pretargeting method, and, importantly, blocking studies demonstrated specificity of tumor uptake of (111)In-labeled biotin in the three-step pretargeting scheme. CONCLUSION: This study demonstrates the use of multivalent bifunctional phage in a three-step pretargeting system for prostate cancer radioimaging.
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Authors | Jessica R Newton-Northup, Said D Figueroa, Thomas P Quinn, Susan L Deutscher |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 36
Issue 7
Pg. 789-800
(Oct 2009)
ISSN: 1872-9614 [Electronic] United States |
PMID | 19720291
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
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Topics |
- Amino Acid Sequence
- Animals
- Bacteriophages
(metabolism)
- Cell Line, Tumor
- Extravasation of Diagnostic and Therapeutic Materials
- Humans
- Immunohistochemistry
- Male
- Mice
- Molecular Sequence Data
- Nanoparticles
- Peptides
(chemistry, metabolism)
- Prostatic Neoplasms
(diagnostic imaging, metabolism)
- Tomography, Emission-Computed, Single-Photon
- Tomography, X-Ray Computed
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