Specific PET Imaging Probes for Early Detection of Prostate Cancer Metastases
Annual rept. 1 May 2009-30 Apr 2010
TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
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Polyarginines are a group of small peptides that have been used as drug delivery vehicles due to their capability of penetrating cell membranes. In one of our studies using such a peptide to deliver a therapeutic moiety to various prostate cancer cell lines, we surprisingly discovered that the peptide had remarkably high preference to prostate tissues. This specificity, which has not been reported before, prompted us to exploit this group of peptides for the early detection of prostate tumor metastases. Promisingly, in our preliminary studies, the peptide labeled with 64Cu can clearly reveal metastases in a tumor-bearing animal model. By two-year work, we have successfully developed an approach to impart multivalency to a bifunctional chelator for targeted PET imaging probe design. This type of multivalent scaffolds features a chelator that forms a stable and neutral complex with a radiometal and multiple functional groups for multimeric presentation of targeting molecules. A bivalent scaffold was synthesized and coupled with an integrin alphasub vbetasub 3 targeting ligand, cRGDyK, to afford a 64Cu-labeled divalent probe. The in vitro and in vivo evaluation clearly demonstrated the divalent probe with the anticipated multivalent effect as compared to its monomeric counterpart. In addition, we have further demonstarted the imaging specificity of 64Cu-DOTA-NHGR11 for prostate cancer detection.
- Medicine and Medical Research