Document Detail


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.
MedLine Citation:
PMID:  16595506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. CONCLUSION: 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:
Shahriar S Yaghoubi; Marcelo A Couto; Chang-Cheng Chen; Lathasree Polavaram; Guanggen Cui; Luyi Sen; Sanjiv S Gambhir
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of nuclear medicine : official publication, Society of Nuclear Medicine     Volume:  47     ISSN:  0161-5505     ISO Abbreviation:  J. Nucl. Med.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-05     Completed Date:  2006-06-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217410     Medline TA:  J Nucl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  706-15     Citation Subset:  IM    
Affiliation:
Department of Radiology, Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Acute Toxicity Tests
Animals
Drug Evaluation, Preclinical
Female
Guanine / analogs & derivatives*,  diagnostic use,  pharmacokinetics,  toxicity
Herpesvirus 1, Human / enzymology*
Male
Mutation
Positron-Emission Tomography
Rabbits
Radiopharmaceuticals / diagnostic use,  pharmacokinetics,  toxicity*
Rats
Rats, Sprague-Dawley
Thymidine Kinase / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/9-(4-fluoro-3-hydroxymethylbutyl)guanine; 0/Radiopharmaceuticals; 73-40-5/Guanine; EC 2.7.1.21/Thymidine Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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