Metabolic and Distribution Studies with Radiolabeled 5-Fluorouracil

Abstract

5-Fluorouracil (5-FU) is an effective anti-tumor drug, which has been used both as a single agent and in combination with other chemotherapeutic agents for the treatment of tumors such as breast and colorectal carcinoma. We synthesized 5-FU with trace amounts of 18F-5-FU and administered the compounds intravenously to 6 cancer patients. The patients were scanned at 2 hr intervals for 12 hrs and their urine collected whenever possible. We also injected 5-FU with the tracer 18F-5-FU, at pharmacological doses, into non-tumored rats, and sampled their bile and blood for 95 mins post-injection. For comparison, 2-14C-5-FU was injected into non-tumored rats and their bile and blood sampled at the same intervals. Minute quantities of rat bile and serum were analyzed chromatographically by high-performance TLC. 5-FU and two of its metabolites (FBAL and FUPA) were identified and quantified by this technique. Both percentage and absolute amounts of 5-FU in the bile follow comparative kinetic patterns. While the liver and the urinary bladder were clearly observable in all 6 patients, the detectability of the gall-bladder was correlated to the inverse of the alkaline phosphatase level in the blood. This work suggests that the diversity of the 5-FU metabolism in cancer patients may allow the use of 18F-5-FU as a probe for understanding those individual variabilities in clinical situations.

Radiolabeling and in vitro evaluation of a new 5‐fluorouracil derivative with cell culture studies

“…Furthermore, Young et al used simple basic radiochemical reactions for the radiolabeling of the 5‐FU. The authors have observed greater than 95% radiochemical purity of this radiolabeled complex . Herein, although the chemical modifications on the main molecule (5‐FU), the radiochemical purity of [ 99m Tc]Tc E was found to be greater than 90%.…”

“…Generally, ideal pH of a radiopharmaceutical is 7.4 or can vary between pH 2.0 and 9.0. According to the Young et al study, the pH of the reaction medium was found to play unimportant role in the labeling process of 5‐FU . While reaction conditions are keeping constant and the reaction pH is varied from pH 5.0 to 7.4, no significant differences were observed on labeling efficiency (Figure ).…”

“…According to the Young et al study, the pH of the reaction medium was found to play unimportant role in the labeling process of 5-FU. 9 While reaction conditions are keeping constant and the reaction pH is varied from pH 5.0 to 7.4, no significant differences were observed on labeling efficiency (Figure 3). According to the result, the pH of the reaction medium was found to play insignificant role in this study too.…”

“…5‐Fluorouracil (5‐FU) is an effective antitumor drug, which has been used either as a single agent or in combination with other chemotherapeutic agents for the treatment of tumors such as breast and colorectal carcinoma . 5‐FU is an antimetabolite drug and works by inhibiting essential biosynthetic processes or by being incorporated into macromolecules, such as DNA and RNA.…”

The Unique Potential for Noninvasive Imaging in Modernizing Drug Development and in Transforming Therapeutics: PET/MRI/MRS

“…While it is viewed as an "old" drug, it continues being used in a very active manner as part of the treatment of many solid tumors (6)(7)(8). My laboratory has performed for years nuclear imaging with 18 F-5FU and, subsequently, 19 F-MRS studies with that drug (9)(10)(11)(12). The unique advantages of both 18 F for PET and 19 F for MRS have been presented above.…”