Different strategies for reducing intestinal background radioactivity associated with imaging HSV1- tk expression using established radionucleoside probes Journal Article

   

Authors:	Ruggiero, A.; Brader, P.; Serganova, I.; Zanzonico, P.; Cai, S.; Lipman, N. S.; Hricak, H.; Blasberg, R. G.
Article Title:	Different strategies for reducing intestinal background radioactivity associated with imaging HSV1- tk expression using established radionucleoside probes
Abstract:	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 fl ora 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 signifi cant 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. © 2010 BC Decker Inc.
Keywords:	positron emission tomography; methodology; radiopharmaceuticals; mouse; animal; metabolism; animals; mice; gene expression; radiation; drug effect; enzymology; radiation exposure; biosynthesis; whole body imaging; rat; radioactivity; positron-emission tomography; radiopharmaceutical agent; drug derivative; uracil arabinoside; arabinofuranosyluracil; ex-vivo; in-vivo; thymidine kinase; herpesvirus 1, human; radioactive tracers; rats; analysis of variance; oligopeptides; herpes simplex virus 1; intestine; intestines; polyethylene glycols; radiation protection; micropet; bacteriology; oligopeptide; background radioactivity; endogenous expression; germ-free mice; intestinal bacteria; intravenous injections; nucleoside analogues; radioactivity level; 2' fluoro 2' deoxy 5 fluoroethyl 1 beta d arabinofuranosyl uracil; 2'-fluoro-2'-deoxy-5-fluoroethyl-1-beta-d-arabinofuranosyl uracil; electrolyte; laxative; macrogol derivative; nulytely; peptamen; gastrointestinal motility; electrolytes; laxatives
Journal Title:	Molecular Imaging
Volume:	9
Issue:	1
ISSN:	1535-3508
Publisher:	Sage Publications, Inc.
Date Published:	2010-02-01
Start Page:	47
End Page:	58
Language:	English
DOI:	10.2310/7290.2010.00006
PUBMED:	20128998
PROVIDER:	scopus
PMCID:	PMC3068838
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-76749157276&partnerID=40&md5=2ef977f93cdab2968bdf5fd5847815eb
Notes:	--- - "Export Date: 20 April 2011" - "Source: Scopus"

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