Different strategies for reducing intestinal background radioactivity associated with imaging HSV1-tk expression using established radionucleoside probes.
One limitation of HSV1-tk reporter positron emission tomography (PET) with nucleoside analogues is the high background radioactivity in the intestine. We hypothesized that endogenous expression of thymidine kinase in bacterial flora could phosphorylate and trap such radiotracers, contributing to the high radioactivity levels in the bowel, and therefore explored different strategies to increase fecal elimination of radiotracer. Intestinal radioactivity was assessed by in vivo microPET imaging and ex vivo tissue sampling following intravenous injection of 18F-FEAU, 124I-FIAU, or 18F-FHBG in a germ-free mouse strain. We also explored the use of an osmotic laxative agent and/or a 100% enzymatically hydrolyzed liquid diet. No significant differences in intestinal radioactivity were observed between germ-free and normal mice. 18F-FHBG-derived intestinal radioactivity levels were higher than those of 18F-FEAU and 124I-FIAU; the intestine to blood ratio was more than 20-fold higher for 18F-FHBG than for 18F-FEAU and 124I-FIAU. The combination of Peptamen and Nulytely lowered intestinal radioactivity levels and increased (2.2-fold) the HSV1-tk transduced xenograft to intestine ratio for 18F-FEAU. Intestinal bacteria in germ-free mice do not contribute to the high intestinal levels of radioactivity following injection of radionucleoside analogues. The combination of Peptamen and Nulytely increased radiotracer elimination by increasing bowel motility without inducing dehydration.
Ruggiero
Alessandro
A
Department of Radiology, Cyclotron and Radiochemistry Core Facility, and Research Animal Resource Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Brader
Peter
P
Serganova
Inna
I
Zanzonico
Pat
P
Cai
Shangde
S
Lipman
Neil S
NS
Hricak
Hedvig
H
Blasberg
Ronald G
RG
D000704:Analysis of Variance; D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004573:Electrolytes / Q000493:pharmacokinetics; D005769:Gastrointestinal Motility / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000528:radiation effects*; D054368:Laxatives / Q000494:pharmacology*; D051379:Mice; D009842:Oligopeptides / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011835:Radiation Protection / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D013937:Thymidine Kinase / Q000032:analysis / Q000096:biosynthesis*; D051598:Whole Body Imaging
C508411:2'-fluoro-2'-deoxy-5-fluoroethyl-1-beta-D-arabinofuranosyl uracil; D004573:Electrolytes; D054368:Laxatives; D009842:Oligopeptides; C073248:Peptamen; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; D011092:Polyethylene Glycols; D013937:Thymidine Kinase; C000595212:polyethylene glycol 3350