title: Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's expression.
abstract: 9-(4-(18)F-Fluoro-3-[hydroxymethyl]butyl)guanine ((18)F-FHBG) is a sensitive and specific PET reporter probe for imaging the PET reporter genes, herpes simplex 1 thymidine kinase (HSV1-tk) and its mutant HSV1-sr39tk. (18)F-FHBG has suitable pharmacokinetics and dosimetry for clinical applications and imaging of HSV1-TK has been demonstrated in the livers of hepatocellular cancer patients.
  
  
  METHODS
  Male and female Sprague-Dawley rats and New Zealand White rabbits were divided into equal groups receiving either 14 microg/kg cold FHBG or carrier solution, for a 14-d acute toxicity assessment. We monitored body weight, food and water consumption, body temperature, cardiovascular electrical and functional indices, respiratory performance and oxygen saturation, comprehensive blood chemistry, complete blood count (CBC), and urinalysis. We conducted daily cage-side examinations for the detection of any clinical abnormalities. Tissues of the animals that were euthanized and necropsied on day 14 were prepared for histopathologic examination.
  
  
  RESULTS
  No significant differences in cardiovascular and respiratory parameters, food consumption, body weight, urine components, or clinical signs attributable to test article toxicity were observed between the treatment and control groups. Any differences noted in the blood chemistry and CBC parameters were deemed to be incidental findings unrelated to the administration of the FHBG.
  
  
  CONCLUSIONS
  Acute toxicity evaluation of FHBG at 100 times the expected human dose does not indicate harm to organ function or tissues. The Food and Drug Administration has approved FHBG as an Investigational New Drug.
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, California, USA.
authors.forename: Shahriar S
authors.initials: SS
authors.lastname: Yaghoubi
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Couto
authors.forename: Chang-Cheng
authors.initials: CC
authors.lastname: Chen
authors.forename: Lathasree
authors.initials: L
authors.lastname: Polavaram
authors.forename: Guanggen
authors.initials: G
authors.lastname: Cui
authors.forename: Luyi
authors.initials: L
authors.lastname: Sen
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D008297:Male; D009154:Mutation; D049268:Positron-Emission Tomography; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D023382:Toxicity Tests, Acute
chemical_list: C113308:9-(4-fluoro-3-hydroxymethylbutyl)guanine; D019275:Radiopharmaceuticals; D006147:Guanine; D013937:Thymidine Kinase