The role of intestinal microflora in nucleoside analog HSV1-TK microPET imaging, different strategies in reducing intestinal background radioactivity

Objectives One limitation of HSV1-tk reporter PET imaging with nucleoside analogs is high intestinal background radioactivity. We hypothesized that endogenous expression of thymidine kinase in bacterial flora could phosphorylate and trap such radiotracers, contributing to high intestinal radioactivity levels. We therefore explored different strategies to accelerate the fecal elimination of the radiotracer.

Methods Intestinal radioactivity was assessedby microPET imaging and ex vivo tissue counting following injection of [¹⁸F]FEAU, [¹²⁴I]FIAU or [¹⁸F]FHBG in bacteria-free mice raised in a sterile environment and in the same strain of animals kept in a normal environment. We explored the use of an osmotic laxative (Nulytely^®) and/or a 100% enzymatically hydrolyzed liquid diet (Peptamen^®).

Results No significant difference in tissue activity by microPET or ex vivo counting was observed between germ-free and control mice. [¹⁸F]FHBG intestinal activity was higher than that of [¹⁸F]FEAU and [¹²⁴I]FIAU in both germ-free and control animals. A two-day treatment with Nulytely increased intestinal and whole-body activity 2-to-5 fold due to uncontrolled dehydration. The combination of Peptamen and Nulytely lowered intestinal activity with a 3-fold decrease in the intestine-to-blood ratio and 2.2-fold increase in the tumor-to-intestine ratio for [¹⁸F]FEAU.

Conclusions Intestinal bacteria do not contribute to high intestinal activities of radionucleoside. The combination of Peptamen and Nulytely increased tracer elimination by increasing bowel motility without significant dehydration and decreased intestinal activity.