A DECREASE IN 1H NUCLEAR MAGNETIC RESONANCE SPECTROSCOPICALLY DETERMINED CITRATE IN HUMAN SEMINAL FLUID ACCOMPANIES THE DEVELOPMENT OF PROSTATE ADENOCARCINOMA
Abstract
Purpose:
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 1H nuclear magnetic resonance (NMR) spectroscopy of unprocessed human seminal plasma as a rapid, noninvasive diagnostic tool for prostate adenocarcinoma.
Materials and 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 1H NMR can be used to measure citrate in seminal fluid, potentially providing a new, rapid, noninvasive screening method.
References
- 1 : Editorial: more information on prostate specific antigen and prostate cancer. J Urol2003; 170: 457. Link, Google Scholar
- 2 : Preoperative serum prostate specific antigen levels between 2 and 22 ng/ml correlate poorly with post-radical prostatectomy cancer morphology; prostate specific antigen cure rates appear constant between 2 and 9 ng./ml. J Urol2002; 167: 103. Link, Google Scholar
- 3 : Localized prostate cancer: relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer1993; 71: 933. Google Scholar
- 4 : Über das vorkommen der zitronensäure in geschlechtsdrusensekreton. Skand Arch Physiol1929; 58: 90. Google Scholar
- 5 : The role of citric acid in the physiology of the prostate: a preliminary report. J Urol1959; 81: 157. Link, Google Scholar
- 6 : Citric acid in human prostatic secretion and metastasizing cancer of prostate gland. Br Med J1962; 5281: 835. Google Scholar
- 7 :
Regulation of citrate related metabolism in normal and neoplastic prostate . In: Endocrine Control in Neoplasia. Edited by . New York: Raven Press1978: 303. Google Scholar - 8 : Citrate in the diagnosis of prostate cancer. Prostate1999; 38: 237. Google Scholar
- 9 : In vivo 13C NMR spectroscopy of the human prostate. Magn Reson Med1988; 8: 224. Google Scholar
- 10 : Differentiation of human tumors from nonmalignant tissue by natural-abundance 13C NMR spectroscopy. Magn Reson Med1988; 7: 384. Google Scholar
- 11 : Carbon-13 and proton nuclear magnetic resonance spectroscopy and microscopy of neoplasms. Adv Pathol1989; 2: 213. Google Scholar
- 12 : 1-Dimensional proton chemical shift imaging of the human prostate in vivo. Proc Soc Magn Reson Med1992; 11: 3305. Google Scholar
- 13 : Proton STEAM spectroscopy of the human prostate in vivo. Proc Soc Magn Reson Med1993; 12: 1029. Google Scholar
- 14 : Zero quantum difference spectroscopy for strongly-coupled systems. J Magn Reson1993; A104: 111. Google Scholar
- 15 : Combined magnetic resonance imaging and spectroscopic imaging approach to molecular imaging of prostate cancer. J Magn Reson Imaging2002; 16: 451. Google Scholar
- 16 : Proton MRS of human prostatic fluid: correlations between citrate, spermine, and myo-inositol levels and changes with disease. Prostate1997; 30: 248. Google Scholar
- 17 : Ultra high field NMR spectroscopic studies on human seminal fluid, seminal vesicle and prostatic secretions. J Pharm Biomed Anal1994; 12: 5. Google Scholar
- 18 : High resolution 1H NMR spectroscopic studies on dynamic biochemical processes in incubated human seminal fluid samples. Biochim Biophys Acta1998; 1379: 367. Google Scholar
- 19 : Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions. J Biomol NMR1992; 2: 661. Google Scholar
- 20 : Magnetic resonance spectroscopy of the malignant prostate gland after radiotherapy: a histopathologic study of diagnostic validity. Int J Radiat Oncol Biol Phys2001; 50: 317. Google Scholar
From the Departments of Biology (TAA), Surgery (EEK, AYS) and Biochemistry and Molecular Biology (LOS), University of New Mexico School of Medicine and Cancer Research and Treatment Center, Albuquerque, New Mexico
