Metabolic response of the CWR22 prostate tumor xenograft after 20 Gy of radiation studied by 1H spectroscopic imaging.
OBJECTIVE
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.


METHODS
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 mm(3), 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, R(2) = 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(2) = 0.02). A constant level of the choline:water ratio (0.010 +/- 0.001; n = 22, R(2) = 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.
Dyke
Jonathan P
JP
Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York 10021, USA.
Zakian
Kristen L
KL
Spees
William M
WM
Matei
Cornelia
C
Chen
Yuchen
Y
Mao
Xiangling
X
Shungu
Dikoma C
DC
Koutcher
Jason A
JA
D000818:Animals; D002794:Choline / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000175:diagnosis / Q000378:metabolism / Q000532:radiotherapy*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy*; D014183:Transplantation, Heterologous
D017430:Prostate-Specific Antigen; D002794:Choline