Document Detail


Evaluation of a 99mTc-labeled AnnexinA5 variant for non-invasive SPECT imaging of cell death in liver, spleen and prostate.
MedLine Citation:
PMID:  19779967     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: We investigate radio-labeling and pharmacokinetics of a new AnnexinA5 variant (HYNIC-cys-AnxA5) and then assess its utility for the non-invasive detection of cell death in liver, spleen and prostate. METHODS: AnnexinA5 binds to phosphatidylserine expressed on the surface of apoptotic and necrotic cells. Contrary to other AnnexinA5 variants, the new cys-AnxA5 allows for site-specific conjugation of a hydrazinonicotinamide-maleimide moiety and subsequent radio-labeling with (99m)Tc at a position not involved in the AnxA5-phosphatidylserine interaction. Distribution of (99m)Tc-HYNIC-cys-AnxA5 was studied in rats, both invasively and via SPECT/CT. Cycloheximide was used to induce cell death in liver and spleen, whereas apoptosis in the prostate was induced by castration. RESULTS: HYNIC-cys-AnxA5 was efficiently and reproducibly labeled with (99m)Tc. Blood clearance of radioactivity after iv-injection was adequately described by a two-compartment model, the renal cortex representing the main site of accumulation. Cycloheximide treatment resulted in increased accumulation of intravenous-injected (99m)Tc-HYNIC-cys-AnxA5 in liver and spleen over controls, which correlated well with TUNEL staining for cell death in corresponding tissue sections. However, the increase in TUNEL-positive prostate epithelial cells observed following castration was not paralleled by greater (99m)Tc-HYNIC-cys-AnxA5 accumulation. CONCLUSION: (99m)Tc-HYNIC-cys-AnxA5 appears a suitable tracer for assessment of cell death in liver and spleen, but not prostate.
Authors:
Rick Greupink; Charles F Sio; Antwan Ederveen; Joke Orsel
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Publication Detail:
Type:  Evaluation Studies; Journal Article     Date:  2009-09-25
Journal Detail:
Title:  Pharmaceutical research     Volume:  26     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2010-01-21     Completed Date:  2010-04-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2647-56     Citation Subset:  IM    
Affiliation:
Schering-Plough Research Institute, Oss, The Netherlands. rick.greupink@spcorp.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Annexin A5 / chemistry,  diagnostic use*,  pharmacokinetics
Cell Death
Cysteine / chemistry
Liver / radionuclide imaging*
Male
Organotechnetium Compounds / diagnostic use*,  pharmacokinetics
Prostate / pathology,  radionuclide imaging*
Rats
Rats, Wistar
Spleen / pathology,  radionuclide imaging*
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Organotechnetium Compounds; 52-90-4/Cysteine

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


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