Metabolic Response of the CWR22 Prostate Tumor Xenograft after 20 Gy of Radiation Studied by H Spectroscopic Imaging

Purpose: The ability to determine the spatial and metabolic distribution of prostate cancer is essential in assessing initial stage, prognosis, and treatment efficacy. Current markers of tumor progression such as prostate-specific antigen (PSA) do not provide spatial information about tumor extent or regions of high metabolic activity. Experimental Design: This study used the androgendependent CWR22 human prostate tumor xenograft in mice to characterize metabolic, PSA, and tumor volume changes that occurred with untreated growth or radiation therapy (XRT). One cohort of mice was studied as the tumor grew to 400 mm, whereas a second cohort was treated with a single 20-Gy fraction of radiation and studied before and 1, 2, and 4 days after XRT. In both cohorts, tumor volume, PSA, and choline:water ratios measured by nuclear magnetic resonance were monitored. Results: The CWR22 tumor had an untreated tumordoubling time of 2.6 0.6 days (n 7). In untreated mice, PSA strongly correlated with tumor volume (P < 0.01, R 0.99). The untreated tumor cohort had a PSA-doubling time of 3.2 0.6 days. Administration of 20 Gy produced a regrowth delay of >15.8 4.8 days (n 6). PSA values after XRT were not correlated with post-XRT tumor volume (P < 0.20, R 0.02). A constant level of the choline:water ratio (0.010 0.001; n 22, R 0.007, P < 0.3) was observed during the course of untreated tumor growth. A statistically significant (P < 0.04, one-tailed t test) 42% decrease in the choline:water ratio at 24 h after administration of XRT preceded observable changes in PSA. Conclusions: Nuclear magnetic resonance spectroscopy provided a method with which to monitor metabolic changes of tumor response to XRT that preceded and predicted PSA and tumor volume changes.