| Abstract
| - As more becomes known about the expression profiles of normal and cancerous cells, it should becomepossible to design antisense-based imaging agents for the early detection of cancer noninvasively. Inthis report, we rationally designed and synthesized three antisense and one sense hybrid PNA (peptidenucleic acid) to the unr mRNA that is highly overexpressed in a breast cancer cell line (MCF-7). Theconjugates had a four-lysine tail at the carboxy terminus for cell permeation and a DOTA (1,4,7,10-tetraazacyclododecane-N,N‘,N‘ ‘,N‘ ‘‘-tetraacetic acid) chelating moiety at the amino terminal end forchelating 64Cu for biodistribution and microPET imaging studies. Biodistribution of two 64Cu-labeledconjugates with antisense and sense sequences (PNA50 and PNA50S) showed high uptake and longretention in kidney and low uptake and efficient clearance in blood and muscle in normal balb/c micewhen administered intravenously or intraperitoneally. Intraperitoneal administration, however, gavea much slower release rate. MCF-7 tumors (100−320 mg) in CB-17 SCID mice were imaged with allfour 64Cu-labeled PNA conjugates by microPET, but the image contrast varied with different timepoints and different conjugates. Of the conjugates studied, 64Cu-DOTA-Y-PNA50-K4 showed the besttumor image quality at all time points with a tumor/muscle ratio of 6.6 ± 1.1 at 24 h postinjection,which is among the highest reported for radiolabeled oligonucleotides. Our work further strengthensthe potential of antigene and antisense PNAs to be utilized as specific molecular probes for earlydetection of cancer and ultimately for patient specific radiotherapy.
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