This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dyke, J. P. Articles by Koutcher, J. A. Search for Related Content PubMed PubMed Citation Articles by Dyke, J. P. Articles by Koutcher, J. A.

Metabolic Response of the CWR22 Prostate Tumor Xenograft after 20 Gy of Radiation Studied by ¹H Spectroscopic Imaging

Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York 10021 [J. P. D.]; Departments of Medical Physics [K. L. Z., W. M. S., C. M., Y. C., J. A. K.], Radiology [K. L. Z., J. A. K.], and Medicine [J. A. K.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021; and Hatch NMR Research Center, College of Physicians and Surgeons, Columbia University, New York, New York 10032 [X. M., D. C. S.]

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 androgen-dependent 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 mm³, 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 tumor-doubling time of 2.6 ± 0.6 days (n = 7). In untreated mice, PSA strongly correlated with tumor volume (P < 0.01, R² = 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, R² = 0.02). A constant level of the choline:water ratio (0.010 ± 0.001; n = 22, R² = 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.