Choline Autoradiography of Human Prostate Cancer Xenograft: Effect of Castration

The purpose of this study was to investigate the effects of castration and tracer uptake time interval on the level of radiolabeled choline accumulation in murine-implanted human prostate tumor xenografts using quantitative autoradiography. We implanted androgen-dependent (CWR22) and androgen-independent (PC3) human prostate cancer cells in castrated ( n = 9) and noncastrated ( n = 9) athymic male mice and allowed tumors to grow to 1 cm 3 . The mice were euthanized at 5, 10, and 20 minutes after injection of 5 µCi [14C]-choline. Mice were prepared for quantitative autoradiography with density light units of viable tumor sections converted to units of radioactivity (nCi/mm 2 ) using calibration. Two-group comparisons were performed using a two-tailed Student t -test with unequal variance and with a significance probability level of less than .05. Two-group comparisons between the means of the tracer uptake level for each tumor type at each of three time points for each of two host types showed that (1) the level of tracer localization in the two tumor types was affected little in relation to the host type and (2) PC3 tumor uptake level tended to increase slowly with time only in the noncastrated host, whereas this was not observed in the castrated host or with CWR22 tumor in either host type. The uptake time interval and castration do not appear to significantly affect the level of radiolabeled choline uptake by the human prostate cancer xenograft

Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG) accumulation in androgen-sensitive (CWR-22) and androgen-independent (PC-3) human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm 3 = 14.913 e 0.108 × days , R 2 = .96, n = 5). The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm 3 = 0.3511 × days 2 + 49.418 × day −753.33, R 2 = .96, n = 3). The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05). The 3-week maximal standardized uptake value (SUV max ) was 0.99 ± 0.43 (mean ± SD ) for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUV max was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUV max was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18%) and the 5-week (by 9.6%) micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer

Choline Autoradiography of Human Prostate Cancer Xenograft: Effect of Castration

The purpose of this study was to investigate the effects of castration and tracer uptake time interval on the level of radiolabeled choline accumulation in murine-implanted human prostate tumor xenografts using quantitative autoradiography. We implanted androgen-dependent (CWR22) and androgen-independent (PC3) human prostate cancer cells in castrated ( n = 9) and noncastrated ( n = 9) athymic male mice and allowed tumors to grow to 1 cm 3 . The mice were euthanized at 5, 10, and 20 minutes after injection of 5 µCi [14C]-choline. Mice were prepared for quantitative autoradiography with density light units of viable tumor sections converted to units of radioactivity (nCi/mm 2 ) using calibration. Two-group comparisons were performed using a two-tailed Student t -test with unequal variance and with a significance probability level of less than .05. Two-group comparisons between the means of the tracer uptake level for each tumor type at each of three time points for each of two host types showed that (1) the level of tracer localization in the two tumor types was affected little in relation to the host type and (2) PC3 tumor uptake level tended to increase slowly with time only in the noncastrated host, whereas this was not observed in the castrated host or with CWR22 tumor in either host type. The uptake time interval and castration do not appear to significantly affect the level of radiolabeled choline uptake by the human prostate cancer xenograft

Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG) accumulation in androgen-sensitive (CWR-22) and androgen-independent (PC-3) human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm 3 = 14.913 e 0.108 × days , R 2 = .96, n = 5). The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm 3 = 0.3511 × days 2 + 49.418 × day −753.33, R 2 = .96, n = 3). The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05). The 3-week maximal standardized uptake value (SUV max ) was 0.99 ± 0.43 (mean ± SD ) for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUV max was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUV max was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18%) and the 5-week (by 9.6%) micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer