A decrease in 1H nuclear magnetic resonance spectroscopically determined citrate in human seminal fluid accompanies the development of prostate adenocarcinoma.
OBJECTIVE
Because human prostatic fluid contributes almost 50% of the volume of seminal plasma and this fluid contains unique prostatic metabolites such as citrate, which are markedly altered during tumorigenesis, we investigated high resolution H nuclear magnetic resonance (NMR) spectroscopy of unprocessed human seminal plasma as a rapid, noninvasive diagnostic tool for prostate adenocarcinoma.


METHODS
Semen and prostatic massage samples from control and tumor bearing subjects were stored frozen at -20C and thawed prior to water suppressed NMR analysis. We found that freezing produced no significant alterations in the semen NMR spectra. Quantitative NMR spectroscopy was performed by first calibrating the water suppression data acquisition sequence with a series of standard samples containing known amounts of citrate within the physiological range.


RESULTS
Well resolved citrate resonances from the seminal plasma of 3 control subjects with prostate specific antigen (PSA) less than 1 ng/ml were integrated to give concentrations of 97 to 178 mM. Semen from a 47-year-old man with benign prostatic hyperplasia and a PSA of 5.5 ng/ml contained 156 mM citrate. In contrast, seminal plasma from 2 patients with prostate cancer, including a 46-year-old man with Gleason grade 8 and PSA 45.2 ng/ml, and a 64-year-old man with grade 6 and PSA 13.0 ng/ml, revealed citrate NMR signals corresponding to a concentration of only 28 and 24 mM, respectively. Spectra from prostatic massage fluid from a normal 23-year-old volunteer showed a citrate of 483 mM, while massage fluid from a 56-year-old patient with Gleason grade 4 cancer showed a citrate of only 1.35 mM.


CONCLUSIONS
To our knowledge this study is the first to use high resolution NMR of semen to diagnose prostate cancer. Given the known effects of adenocarcinoma on prostate metabolism, the study indicates that high resolution H NMR can be used to measure citrate in seminal fluid, potentially providing a new, rapid, noninvasive screening method.
Averna
Tiffany A
TA
Department of Biology, University of New Mexico School of Medicine and Cancer Research and Treatment Center, Albuquerque, New Mexico 87131, USA.
Kline
Eric E
EE
Smith
Anthony Y
AY
Sillerud
Laurel O
LO
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D019343:Citric Acid / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D011522:Protons; D012661:Semen / Q000737:chemistry* / Q000378:metabolism
D011522:Protons; D019343:Citric Acid