Copper-64 as a radiopharmaceutical for canine prostate imaging

Abstract

Human prostate cancer has a 17% incidence in men over 55 years of age, with only a 55% survival rate after 5 years of treatment. Presently, no diagnostic procedure is very effective in detecting the early stages of prostatic cancer. This study used non-invasive scintigraphy of dogs having enlarged prostate glands. Three different radiopharmaceuticals labeled with Copper-64 were evaluated. Copper-64 was produced using an 8-hour (n,(gamma)) activation reaction. The Copper-64 was exchanged with two proteins superoxide dismutase (SOD) and ceruloplasmin (CP) . Either one of these radiopharmaceuticals or radioactive cupric sulfate (('64)CuSO(,4)) was injected intravenously into 18 dogs, subdivided into three groups. Three dogs with prostatic cancer were also injected with ('64)CuSO(,4). The ('64)CuSO(,4) had the shortest biologic half-life and had similar distribution and clearance to CP. Signs of acute copper toxicity were observed in one-third of the dogs. Fifteen of eighteen dogs scanned, through the use of a gamma camera, had increased levels of radioactivity. There was a good correlation between the positive scans, histopathology and radiography. Tissue concentrations of Copper-64 within the prostate, liver, and kidney were further evaluated. No significant difference (p > 0.1) was seen in the uptake by the prostate for any of the three copper radiopharmaceuticals. However, the uptake was significantly different (p < 0.0005) for dogs with neoplasia. The relative tissue uptake (RTU) by the prostate was significantly higher (p < 0.05) for ('64)CuSO(,4) compared to SOD and CP. The liver had approximately a 70 times greater concentration of Copper-64 than the prostate. SOD had relatively high concentrations in the kidney. Copper and zinc concentrations in normal canine prostates were also evaluated as part of this project. The mean copper content in 16 glands was 20.3 (+OR-) 7.1 micrograms per gram of tissue (wet weight), and the zinc to copper ratio was 10.5 to 1. This study revealed that Copper-64 concentrated significantly in the canine prostate, especially within enlarged, diseased glands. Scintillation imaging was possible. Copper-67, however, would be a superior radioisotope of copper for scintigraphy, because of its longer physical half-life and lower (gamma)-ray energy (0.184 MeV). Further experimental trials seem justified using Copper-67 to image the prostate. These results also suggest that copper may be an important element in future imaging of cancer patients with nuclear magnetic resonance.