Citrate alterations in primary and metastatic human prostatic adenocarcinomas: ¹H magnetic resonance spectroscopy and biochemical study

Abstract

The objectives of this study were to quantitatively verify the low levels of citrate previously observed in primary human prostatic adenocarcinomas and to determine whether citrate was further reduced in metastatic prostatic cancer. This was accomplished by comparison of citrate concentrations of DU 145 xenografts (a poorly differentiated human prostatic adenocarcinoma cell line grown in nude mice) with concentrations in primary human adenocarcinomas. Following in vivo 1H NMR studies of DU 145 xenografts, citrate concentrations of DU 145 xenografts and surgically removed primary prostatic adenocarcinoma tissue were determined by quantitative high resolution 1H NMR and enzymatic assay. The most significant findings of this study were that citrate concentrations in primary human adenocarcinomas (3.74 +/- 0.19 mumol/g wet weight) were significantly lower than those observed for normal and benign hyperplastic (BPH) prostatic tissues. Furthermore there was a further ten-fold reduction of citrate associated with DU 145 xenografts (0.31 +/- 0.028 mumole/g wet weight) compared with primary prostatic cancer. DU 145 xenografts also exhibited higher levels of uridine diphosphosugars and choline containing metabolites relative to primary prostatic adenocarcinomas. These findings support the hypothesis that citrate is low in primary prostatic cancer and further reduced in metastatic disease.

Effect of Cation Binding on the Proton Chemical Shifts and the Spin–Spin Coupling Constant of Citrate

“…A possible explanation for this discrepancy may be the low ratio between the citrate concentration and the total cation concentration. Only for this sample with a citrate concentration of 30 m M is this ratio lower than 2 , which means that a high percentage of the carboxylate groups is associated with a divalent cation.…”

Citrate in Pediatric CNS Tumors?

“…Citrate is thus an important in vivo marker of a malignant process. [8][9][10][11] Citrate concentrations in brain tissue (approximately 0.4 mmol/kg 12,13 ) and CSF (approximately 0.2 mmol/L 14 ) are very low, and, to the best of our knowledge, citrate has not been identified with in vivo MR spectroscopy in human brain tissue. …”

Citrate in the diagnosis of prostate cancer

“…Beginning in 1989, Narayan et al [14][15][16][17][18], developed the technique of performing human MRS studies using an endorectal coil. Initial feasibility studies with small surface coils were performed on Dunning rat prostate cancers grown on the flank, which led to the subsequent development of single-and double-tuned endorectal coils.…”