JNM: PET could help elucidate gastrointestinal drug absorption
PET technology is a powerful tool for in vivo analysis of the gastrointestinal absorption of orally administered drugs, based on a study of conscious and anesthetized rats, published in the February issue of the Journal of Nuclear Medicine.

In preclinical animal studies, in vivo gastrointestinal absorption of drugs is usually assessed by pharmacokinetic analysis of the time course of drug concentration in the blood—an assessment that may give simple and overall parameters such as ka and bioavailability. However, according to the study authors, if the in vivo process of gastrointestinal drug absorption is unclear, it will be difficult to understand why changes in the physiologic conditions of the gastrointestinal tract cause absorption to fluctuate.

Therefore, Shinji Yamashita, MD, from the department of pharmaceutical sciences at Setsunan University in Osaka, Japan, and colleagues used 18F-FDG as a model probe orally administered to rats as a solution. They obtained PET scans of the whole body and abdominal region under conscious and anesthetized conditions and routinely took blood samples from the femoral vein during scanning.

The investigators estimated the rate of gastric emptying and intestinal absorption of 18F-FDG from the time profiles of radioactivity in the stomach and small intestine. In addition, nonradiolabeled 2-fluoro-2-deoxy-D-glucose (2-FDG) was used in an intestinal closed-loop experiment to compare the intestinal permeability of 2-FDG with that of D-glucose.

In conscious rats, Yamashita and colleagues found that the gastrointestinal absorption of 18F-FDG was rate-limited by the process of intestinal membrane permeation because the permeability of 2-FDG through the intestinal membrane was low compared with that of D-glucose.

In anesthetized rats, the gastric emptying rate of 18F-FDG decreased dramatically whereas the intestinal absorption rate constant was not significantly different from that in conscious rats, according to the authors. As a result, the rate-limiting step of gastrointestinal absorption of 18F-FDG was shifted to the gastric emptying process by anesthesia.

Based on their results, the authors concluded that they “successfully demonstrated that PET is highly capable of visualizing and kinetically analyzing the gastrointestinal absorption of drugs in vivo. Most PET studies have been performed by intravenous injection of radiolabeled probes in animals or humans; ours appears to be the first report in which PET technique was applied to the study of gastrointestinal drug absorption.”