Abstract 3227: Evaluation of prostate cancer metabolomic field effects with 1H HRMAS MRS and prostate needle biopsies.
Authors: Decelle Emily A. , Berker Yannick , Schwessinger Tilman , Wu Shulin , McDougal W Scott , Wu Chin-Lee , Cheng Leo L. 
Published: August 2014

Purpose: Randomly conducted prostate biopsies often result in false negatives for early-stage PCa patients. Results from our previous studies of intact tissue samples from PCa patients suggested the existence of metabolomic fields, where PCa metabolic information delocalizes from PCa glands and into surrounding benign structures, likely creating PCa “metabolomic lesions” that are larger than the histology cancer lesions. We designed the current study to test the metabolomic field hypothesis by evaluating prostate biopsy cores.

Methods: We collected an additional prostate needle biopsy from patients undergoing trans-rectal ultrasound (TRUS) guided biopsy, with the location recorded, for MR analysis. MR experiments were carried out on a Bruker AVANCE spectrometer operating at 600 MHz (14.1T) and pre-cooled to 4°C. A 4mm zirconia rotor was used with inserts to create a 10μl sample space, and D2O was added for 2H field locking. Spectra were acquired using slow spinning rates of 600 and 700Hz and post-spectral edited with Min(A, B) scheme. Spectroscopic data were processed using an in-house MatLab based program. Following MRS analysis, the analyzed core from each patient was evaluated by histopathology and included in the final pathology report along with the other biopsy cores from the same patient.

Results: Our studies have shown that spectral regions measured from histologically benign (Hb) samples, and the metabolomic profiles calculated according to principal component (PC) analysis, could differentiate pathological stage (pT) (T2ab, T2c, and T3) and the Gleason score (GS)7 group from GS6 and GS5, as well as identify cases of low aggressive potential, defined as GS≤6 and T2. Among the 111 measured biopsy cores, to evaluate the spatial distribution of the hypothesized PCa metabolomic fields, we identified the following four patient groups. A) The measured biopsy cores contained PCa glands (n=14), and for the cases where the measured cores were Hb: B) PCa glands were detected from the same quadrant by another biopsy core (n=13), C) PCa glands were seen in the adjacent quadrants (n=26), and D) PCa glands were located in the further away quadrants (n=15). Our results using the biopsy samples show that a number of spectral regions and profiles display significant differences among the four groups, including taurine at 3.43 ppm (p=0.0003), alanine at 1.47 (p=0.0011), PC1 (p=0.0001), and PC4 (p&lt;0.0001).

Conclusions: Our results presented here demonstrate the existence of PCa metabolomic fields. While more systematically designed studies are necessary to fully evaluate and understand the extent of the fields, the existence of these fields, nevertheless, presents an immediate clinical implication: with the enlarged PCa “metabolomic lesions," the implementation of PCa metabolomic imaging may realize the widely searched goal of targeted PCa biopsy to overcome the current histology error seen in the PCa clinic.

Citation Format: Emily A. Decelle, Yannick Berker, Tilman Schwessinger, Shulin Wu, W Scott McDougal, Chin-Lee Wu, Leo L. Cheng. Evaluation of prostate cancer metabolomic field effects with 1H HRMAS MRS and prostate needle biopsies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3227. doi:10.1158/1538-7445.AM2013-3227