Mapping the biodistribution and catabolism of 5‐fluorouracil in tumor‐bearing rats by chemical‐shift selective ¹⁹F MR imaging

Abstract

A chemical-shift selective (CHESS) 19F MR imaging technique was used to map selectively the antineoplastic drug 5-fluorouracil (5-FU) and its major catabolite alpha-fluoro-beta-alanine (FBAL) in tumor-bearing rats. The pulse sequence employed a CHESS RF saturation pulse to suppress either the 5-FU or the FBAL resonance before the other component in the two-line 19F MR spectra was measured. Selective 5-FU and FBAL images with a spatial resolution of 10 x 10 x 15 mm3 (1.5 ml) were obtained in 40 min from six ACl rats with implanted Morris hepatoma. Because the transmitter frequency could always be set to the Larmor frequency of the 19F resonance employed for imaging, the images were free of chemical-shift artifacts in readout and slice-selection direction. Whereas FBAL appeared only in the liver, the kidneys, and the bladder, 5-FU could also be detected in all major organs and in the muscular system. In the Morris hepatomas, a small 5-FU uptake and no FBAL accumulation were measured. The CHESS 19F MRI technique provides useful physiological and biochemical data on the biodistribution of the antineoplastic drug 5-FU and on the different catabolic activities of the tissues.

Fluorine-19 Fast Recovery Fast Spin Echo Imaging for Mapping 5-Fluorouracil

“…To investigate the distribution of 5-FU and its metabolites, conventional chemical shift imaging has been utilized, but spatial resolution is relatively low. 10,11 For fast acquisition of 19 F metabolite maps of 5-FU, chemical shift selective FLASH 12,13 or FSE 2 has also been reported. As shown, the T1 of the 19 F signal of 5-FU solution used was 2300 ms. Short TR reduces acquisition time but is not suitable to detect NMR signals having such a long T1.…”

“…We recognize that the sensitivities of our 19 F images are not as good as those previously reported. 2,12,13 As Brix and colleagues reported, high signal in the bladder disturbs the detection of low signals in other organs, and they remove urine with a catheter. We therefore infused a smaller dose of 5-FU continuously for 30 min in the magnet.…”

Importance of Fluorine and Fluorocarbons in Medicinal Chemistry and Oncology

“…specific tissue uptake such as liver and kidneys, in case of 5-FU) and catabolism (i.e. major catabolite such as α-fluoro-β-alanine was detected in case of 5-FU) in tumor-bearing rats [42,43].…”

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

“…However, to date the method has not been translated to the routine clinical setting, since most clinical MRI scanners lack a 19 F capability. PFCs have been observed in patients following administration as adjuvant to radiotherapy and as residues in the eye, where they are used as tamponades during retinal surgery (127,137,138 (140)(141)(142)(143). Even then, R 1 sensitivity to oxygen is low (B'= 0.0002 s -1 /torr) and to temperature is high.…”

“…FBAL is excreted by the kidneys. Localized NMR spectroscopy and low resolution CSI have examined pharmacokinetics [103,[136][137][138]. NMR of excised tissue and body fluids has also provided insight into metabolism and can provide much higher sensitivity (e.g., mM).…”