Document Detail

[¹¹C]Rhodamine-123: synthesis and biodistribution in rodents.
MedLine Citation:
PMID:  22898316     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Rhodamine-123 is a known substrate for the efflux transporter, P-glycoprotein (P-gp). We wished to assess whether rhodamine-123 might serve as a useful substrate for developing probes for imaging efflux transporters in vivo with positron emission tomography (PET). For this purpose, we aimed to label rhodamine-123 with carbon-11 (t(1/2)=20.4min) and to study its biodistribution in rodents.
METHODS: [¹¹C]Rhodamine-123 was prepared by treating rhodamine-110 (desmethyl-rhodamine-123) with [¹¹C]methyl iodide. The biodistribution of this radiotracer was studied with PET in wild-type mice and rats, in efflux transporter knockout mice, in wild-type rats pretreated with DCPQ (an inhibitor of P-gp) or with cimetidine (an inhibitor of organic cation transporters; OCT), and in P-gp knockout mice pretreated with cimetidine. Unchanged radiotracer in forebrain, plasma and peripheral tissues was also measured ex vivo at 30min after radiotracer administration to wild-type and efflux transporter knockout rodents.
RESULTS: [(¹¹C]Rhodamine-123 was obtained in 4.4% decay-corrected radiochemical yield from cyclotron-produced [¹¹C]carbon dioxide. After intravenous administration of [¹¹C]rhodamine-123 to wild-type rodents, PET and ex vivo measurements showed radioactivity uptake was very low in brain, but relatively high in some other organs such as heart, and especially liver and kidney. Inhibition of P-gp increased uptake in brain, heart, kidney and liver, but only by up to twofold. Secretion of radioactivity from kidney was markedly reduced by OCT knockout or pretreatment with cimetidine.
CONCLUSIONS: [¹¹C]Rhodamine-123 was unpromising as a PET probe for P-gp function and appears to be a strong substrate of OCT in kidney. Cimetidine appears effective for blocking OCT in kidney in vivo.
Xiaofeng Bao; Shuiyu Lu; Jeih-San Liow; Cheryl L Morse; Kacey B Anderson; Sami S Zoghbi; Robert B Innis; Victor W Pike
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2012-08-14
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  39     ISSN:  1872-9614     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2013-03-28     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1128-36     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1003, USA.
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MeSH Terms
Biological Transport / drug effects
Carbon Radioisotopes / diagnostic use
Chemistry Techniques, Synthetic
Cimetidine / pharmacology
Dibenzocycloheptenes / pharmacology
Gene Knockout Techniques
Kidney / drug effects,  metabolism
Liver / drug effects,  metabolism
Organic Cation Transport Proteins / antagonists & inhibitors,  metabolism
P-Glycoprotein / antagonists & inhibitors,  deficiency,  genetics,  metabolism
Positron-Emission Tomography
Quinolines / pharmacology
Radioactive Tracers
Rhodamine 123 / chemical synthesis*,  diagnostic use,  metabolism,  pharmacokinetics*
Tissue Distribution
Grant Support
Reg. No./Substance:
0/Carbon Radioisotopes; 0/Dibenzocycloheptenes; 0/Organic Cation Transport Proteins; 0/P-Glycoprotein; 0/Quinolines; 0/Radioactive Tracers; 51481-61-9/Cimetidine; 62669-70-9/Rhodamine 123; 813AGY3126/zosuquidar trihydrochloride

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

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