Noninvasive Phosphorus Magnetic Resonance Spectroscopic Imaging Predicts Outcome to First-line Chemotherapy in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma

Abstract

Rationale and Objectives Based on their association with malignant proliferation, using noninvasive phosphorus MR spectroscopic imaging (31P MRSI), we measured the tumor content of the phospholipid-related phosphomonoesters (PME), phosphoethanolamine and phosphocholine and its correlation with treatment outcome in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients receiving standard first-line chemotherapy. Experimental Design The PME value normalized to nucleoside triphosphates (PME/NTP) was measured using 31P MRSI in tumor masses of 20 DLBCL patients prior to receive standard first-line chemotherapy. Response at six months was complete in 13 patients and partial in seven. Time to treatment failure (TTF) was ≤11 months in eight patients, from 18 to 30 months in three, and ≥ 60 months in nine. Results On a t-test, the pretreatment tumor PME/NTP mean value (SD, n) of patients with a complete response at six months was 1.42 (0.41, 13), which was significantly different from the value of 2.46 (0.40, 7) in patients with partial response (p < 0.00001). A Fisher test significantly correlated the PME/NTP values with response at six months (sensitivity and specificity at 0.85, p < 0.004) while a Cox proportional hazards regression significantly correlated the PME/NTP values with TTF (hazard ratio=5.21, p < 0.02). A Kaplan-Meier test set apart a group entirely composed of patients with TTF ≤ 11 months (hazard ratio=8.66, p<0.00001). Conclusion The pretreatment tumor PME/NTP values correlated with response to treatment at six months and time to treatment failure in newly diagnosed DLBCL patients treated with first-line chemotherapy and therefore they could be used to predict treatment outcome in these patients.

Radiotherapy planning using MRI

“…In oncology 31P MRS is most used to monitor tumour response to therapy, especially in the new era of targeted treatments that are designed to block specific signalling pathways (Glunde et al, 2011a). Pretreatment 31P MR spectra have also been shown potential to predict final tumour response (Arias-Mendoza et al, 2013). 13C nuclei have only 1% natural abundance, as well as intrinsically only yielding 1.6% of the signal of 1H nuclei.…”

PHOSPHO1 Serves as a Key Metabolism-Related Biomarker in the Tumorigenesis of Diffuse Large B-cell Lymphoma

“…Generally, PHOSPHO1 is correlated with the production of inorganic phosphate (Pi) for matrix and skeletal mineralization [36] . Activation of cytosolic PE metabolism decreases the mitochondrial respiration activity and increases glycolysis [37] . Furthermore, PE values before cancer treatment are related to the response to medication at 6th month and the time to therapy failure in DLBCL patients [38] .…”

In vitro nuclear magnetic resonance spectroscopy metabolic biomarkers for the combination of temozolomide with PI3K inhibition in paediatric glioblastoma cells

“…This involves monitoring changes in PC and GPC levels with 31 P-MRS or using 1 H-MRS to detect lactate and tCho. Innovative 31 P-MRS approaches based on 1 H/ 31 P polarization transfer are being developed to improve in vivo detection and quantification of phosphomonoesters including phosphoethanolamine (PE) and PC, and phosphodiesters including glycerophosphoethanolamine (GPE) and GPC, non-invasively on small animal and clinical MR scanners [ 45 , 48 , 49 ]. Concerning the detection of lactate, many mechanisms could contribute to the steady-state lactate signal that is observed using 1 H-MRS in vivo , and hence interpreting lactate using this methodology remains complex [ 50 ].…”