Metabolic and distribution studies with radiolabeled 5-fluorouracil

Area of Science:

• Pharmacology
• Radiochemistry
• Oncology

Background:

• 5-Fluorouracil (5-FU) is a key chemotherapy agent for breast and colorectal cancers.
• Understanding 5-FU metabolism is crucial for optimizing cancer treatment.
• Individual variations in drug metabolism can impact treatment efficacy.

Purpose of the Study:

• To synthesize and utilize 18F-5-FU as a radiotracer for pharmacokinetic studies.
• To investigate the metabolism and distribution of 5-FU in cancer patients and rats.
• To explore the potential of 18F-5-FU in assessing inter-individual variability in 5-FU metabolism.

Main Methods:

• Intravenous administration of 18F-5-FU and 5-FU to 6 cancer patients.
• Pharmacokinetic sampling (urine, blood, bile) and imaging in patients and rats.
• High-performance thin-layer chromatography (TLC) for metabolite identification and quantification (5-FU, FBAL, FUPA).

Main Results:

• The liver and urinary bladder were visualized in all patients.
• Gallbladder detectability correlated inversely with alkaline phosphatase levels.
• Comparative kinetic patterns of 5-FU in rat bile were observed using 18F-5-FU and 2-14C-5-FU.

Conclusions:

• 18F-5-5-FU serves as a viable radiotracer for studying 5-FU pharmacokinetics.
• Individual differences in 5-FU metabolism are significant in cancer patients.
• 18F-5-FU shows promise as a probe to understand patient-specific 5-FU metabolism variability.