Academic literature on the topic 'NMR 1H-MRS Prostate Citrate'

4623 Background: Nuclear magnetic resonance spectroscopy (NMRS) along with a novel method for determining absolute concentrations of metabolites were utilized to analyze expressed prostatic secretions (EPS) from men with prostate cancer (PCa) and from healthy controls. Methods: Flash frozen EPS samples from 66 men (40 with PCa and 26 controls) were analyzed by high-resolution 1H-NMR spectroscopy using a Bruker 500 MHz DRX NMR spectrometer with a 1-mm microprobe. The total number of scans per fully relaxed 1H-NMR spectrum was n = 40 with water suppression. Absolute concentrations of endogenous metabolites (citrate, spermine, myo-inositol, lactate, alanine, phosphocholine, glutamate, acetate, hydroxybutyrate) were quantified using trimethylsilyl-propionic acid as an external standard reference. Stepwise multivariable logistic regression (LR) was used to model the risk of PCa based upon the levels of the measured metabolites. Results: The average age of the EPS donors was 54.7 ± 9.8 years. The median Gleason score for the men with PCa was 6 (range 5–9). The Wilcoxon rank sum test indicated that citrate, spermine, inositol, citrate/spermine, and citrate/lactate were all significant predictors of PCa (p < .001). The LR models indicated that the absolute concentration of citrate was highly predictive of PCa with lower concentrations resulting in a higher risk of cancer. The area under the receiver operating characteristic curve (AUROC) for citrate alone was 0.79 (95% CI 0.75–0.83). Using relative concentrations (metabolite ratios) in a two-variable LR model, citrate/spermine and citrate/lactate were also predictive of PCa with an AUROC of 0.76 (95% CI 0.71–0.81). Conclusions: The results suggest that absolute concentration of citrate and its derivatives in EPS as measured by NMRS have promising potential as accurate markers of prostate cancer. No significant financial relationships to disclose.

The use of magnetic resonance spectroscopy (MRS) for the detection of in-vivo metabolic perturbations is increasing in popularity in Prostate Cancer (PCa) research on both humans and rodent models. However, there are distinct metabolic differences between species and prostate areas; a fact making general conclusions about PCa difficult. Here, we use High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) spectroscopy to provide tissue specific identification of metabolites and their relative ratios; information useful in providing insight into the biochemical pathways of the prostate. As our NMR-based approach reveals, human and rat prostate tissues have different metabolic signatures as reflected in numerous key metabolites, including citrate and choline compounds, but also aspartate, lysine, taurine, glutamate, glutamine, creatine and inositol. In general, distribution of these metabolites is not only highly dependent on the species (human versus rat), but also on the location (lobe/zone) in the prostate tissue and the sample pathology; an observation making HRMAS NMR of intact tissue samples a promising method for extracting differences and common features in various experimental prostate cancer models.

e16136 Background: ETRR in PCa remains a challenging task. New biomarkers in the form of metabolites, detected with Proton Magnetic Resonance Spectroscopy (1H-MRS), and quantitative Apparent Diffusion Coefficient (ADC), determined with Diffusion-Weighted Magnetic Resonance Imaging, could be of value in the ETRR for PCa. Methods: Twenty-one men with biopsy proven localized PCa were examined before external radiotherapy. 3D-1H-MRS was performed at 3.0T without endorectal coils. The delivered radiotherapy dose was 78 Gy in 39 fractions with 6 MV photons. MR follow-up examinations up to 36 months post-radiotherapy were performed. For the pre-clinical study, healthy rat prostate was studied in 3 nude rats. PC3-MM2 and PAC-120 tumors were subcutaneously (SC) and orthotopically (OT) xenografted in 5 nude rats, respectively. Radiotherapy anti-tumor efficacy administered as HDR-brachytherapy (SC) or X6 external beam irradiation (OT) delivering 10 Gy/5 fractions was evaluated. 1H-MRS was performed at 4.7 T using SVS. Results: Twelve men received the 3-month examination, 8 patients are at 6-months, 4 are at 9 months and 1 has been followed for 1 year. At baseline, healthy prostate shows a low Choline (Cho)/Citrate ratio, whereas the presence of cancer considerably increases this ratio. At 3 months, we observed metabolic atrophy except for Cho. Although, higher ADC values are normally found in peripheral zone than in central gland, these differences disappear after radiotherapy. In healthy rat prostate high levels of Cho without citrate were noted. Cho and free lipids were detected in PC3-MM2 and PAC120 SC-grafted tumors, with a higher Cho content in PC3-MM2. Radiotherapy induced significant antitumor activity in PC3-MM2 (SC) (T/C% = 38%) and OT (ILS% = 58%) tumors, but was not efficient in PAC120 SC-grafted tumors (T/C% = 90%). Radiotherapy slightly modified Cho content 4 days after the end of treatment but no modification on overall metabolic profile was observed before, during and after radiotherapy. Conclusions: Combined ADC and Cho are powerful biomarkers for the detection of PCa in men and could be useful for ETRR.The use of Cho in ETRR for PCa in rats appears to be promising. No significant financial relationships to disclose.

Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified fatty acids (NEFA), the main substrate for synthesis of intrahepatic triglycerides (IHTG). To explore the underlying mechanism, we quantified hepatic mitochondrial fluxes and their regulators in humans by using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects received stable isotope infusions of: [D7]glucose, [13C4]β-hydroxybutyrate and [3-13C]lactate before and after a 6-d KD. IHTG was determined by proton magnetic resonance spectroscopy (1H-MRS). The KD diet decreased IHTG by 31% in the face of a 3% decrease in body weight and decreased hepatic insulin resistance (−58%) despite an increase in NEFA concentrations (+35%). These changes were attributed to increased net hydrolysis of IHTG and partitioning of the resulting fatty acids toward ketogenesis (+232%) due to reductions in serum insulin concentrations (−53%) and hepatic citrate synthase flux (−38%), respectively. The former was attributed to decreased hepatic insulin resistance and the latter to increased hepatic mitochondrial redox state (+167%) and decreased plasma leptin (−45%) and triiodothyronine (−21%) concentrations. These data demonstrate heretofore undescribed adaptations underlying the reversal of NAFLD by KD: That is, markedly altered hepatic mitochondrial fluxes and redox state to promote ketogenesis rather than synthesis of IHTG.

Il cancro della prostata (PCa) è il tumore maligno non-cutaneo più diffuso tra gli uomini ed è il secondo tumore che miete più vittime nei paesi occidentali. La necessità di nuove tecniche non invasive per la diagnosi precoce del PCa è aumentata negli anni. 1H-MRS (proton magnetic resonance spectroscopy) e 1H-MRSI (proton magnetic resonance spectroscopy imaging) sono tecniche avanzate di spettroscopia in risonanza magnetica che permettono di individuare presenza di metaboliti come citrato, colina, creatina e in alcuni casi poliammine in uno o più voxel nel tessuto prostatico. L’abbondanza o l’assenza di uno di questi metaboliti rende possibile discriminare un tessuto sano da uno patologico. Le tecniche di spettroscopia RM sono correntemente utilizzate nella pratica clinica per cervello e fegato, con l’utilizzo di software dedicati per l’analisi degli spettri. La quantificazione di metaboliti nella prostata invece può risultare difficile a causa del basso rapporto segnale/rumore (SNR) degli spettri e del forte accoppiamento-j del citrato. Lo scopo principale di questo lavoro è di proporre un software prototipo per la quantificazione automatica di citrato, colina e creatina nella prostata. Lo sviluppo del programma e dei suoi algoritmi è stato portato avanti all’interno dell’IRST (Istituto Romagnolo per lo Studio e la cura dei Tumori) con l’aiuto dell’unità di fisica sanitaria. Il cuore del programma è un algoritmo iterativo per il fit degli spettri che fa uso di simulazioni MRS sviluppate con il pacchetto di librerie GAMMA in C++. L’accuratezza delle quantificazioni è stata testata con dei fantocci realizzati all’interno dei laboratori dell’istituto. Tutte le misure spettroscopiche sono state eseguite con il nuovo scanner Philips Ingenia 3T, una delle machine di risonanza magnetica più avanzate per applicazioni cliniche. Infine, dopo aver eseguito i test in vitro sui fantocci, sono stati acquisiti gli spettri delle prostate di alcuni volontari sani, per testare se il programma fosse in grado di lavorare in condizioni di basso SNR.