Early diagnosis of prostate cancer by citrate determination in urine with europium-oxytetracycline complex.

Normal prostate tissue contains high levels of citrate. In the presence of prostate cancer, the citrate level is diminished. In this paper we show that it is possible to use europium-oxytetracycline complex as a citrate fluorescent probe and consequently as a prostate cancer probe. We analyzed normal nude male mice urine and urine from nude male mice in which prostate cancer was induced by intraprostatic inoculation of DU145 cells. The urine samples were collected from the animals at the 7th, 14th, 21st, and 35th days after the surgery procedures. The intensity of europium emission at 615 nm in europium-oxytetracycline complex in the presence of citrate increases linearly. The citrate concentrations were determined from a calculated calibration curve. A concentration decrease in malignant prostate urine from the normal (PBS group) urine value from ~8.0 mM to ~2.4 mM (tumor group at 35th day) was found. The obtained results indicated that europium-oxytetracycline provides a significant biomarker for prostate cancer detection with a direct, accurate, noninvasive, and non-enzymatic method for measurement of citrate in biological fluids.