Multinuclear MR investigation of the metabolic response of the murine RIF‐1 tumor to 5‐fluorouracil chemotherapy

Abstract

The metabolic response of the RIF-1 tumor to 5-fluorouracil (a single dose of 260 mg 5FU/kg, ip) was monitored in 10 mice using 19F and 31P MR spectroscopy. 19F MRS revealed a continuous drop in tumor 5FU level and an increase in the fluoronucleotide (Fnuc) signal to a plateau value of 50% of the initial 5FU level, during the first 2 h after chemotherapy. Although the 31P MR spectra of the tumors showed no significant initial changes, the total level of MR visible tumor phosphate decreased and tumor pH increased during the subsequent days. The changes in phosphate metabolism and tumor pH did not correlate with the detected fluorine levels or tumor response. However, the pretreatment Pi level, the plateau Fnuc level, and the 5FU induced decrease in tumor volume showed significant correlation. This indicates that both 19F and 31P MR spectroscopy have potential for predicting response to 5FU chemotherapy.

Changes of 31P-MR Spectroscopy in Experimental Tumors Following Radiotherapy Compined with 5-Fluorouracil Compound(UFT).

“…215 al. 1990; Allavena et al 1991;Sijens et al 1991). The correlation between the therapeutic effects and the changes in 19F-MRS, which have been used to monitor the uptake and metabolism of 5-FU in tumor tissue after administration, have not been made clear (Koutcher et al 1991; Sij ens and Ng 1992).…”

Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma

“…19 F magnetic resonance spectroscopy (MRS) is a powerful method for assessing these aspects in vivo since it allows the noninvasive detection and quantitation of 5-FU and its metabolites in tumour during therapy. Such experiments have been described for a number of animal models (Stevens et al, 1984;McSheehy et al, 1989;Koutcher et al, 1991;Sijens et al, 1991). However, the clinically relevant problem of why various tumours and patients exhibit widely differing sensitivities to 5-FU therapy has, up to now, not been investigated in detail by this method.…”

VatuximabTM: Optimizing Therapeutic Strategies for Prostate Cancer Based on Dynamic MR Tumor Oximetry

“…One key difference in this 1 H MR approach compared to 19 F oximetry is the need to effectively suppress water and fat signals and perform relaxometry on the silane signal. In PISTOL, we have developed an effective approach using a combination of frequency selective excitation of the silane resonance and CHESS (148) suppression of the water and fat resonances is used followed by EPI detection for measuring T 1 values (144). As with HFB, ARDVARC (Alternating Relaxation Delays with Variable Acquisitions for Reduction of Clearance effects) protocol (98) is used in conjunction with this sequence to obtain T 1 values.…”

“…2). Intriguingly, fluoronucleotides derived in vivo from 5FU exhibit sensitivity to changes in pH and could be used to measure intracellular pH (pHi), although the presence of a mixture of products may complicate interpretation [141,144,145]. Given the inherent dose-limiting toxicity of 5FU, various prodrugs and mixture formulations have been developed (e.g., capecitabine (Xeloda), Tegafur-uracil (Uftoral ® ), emitefur (3 (3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl)-1-ethoxymethyl-5-fluorouracil)) and 19 F NMR has played a role in analysis and development [16,63].…”