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[18F]Fluoro-Deoxy-Glucose Folate - A Novel PET Radiotracer with Improved In Vivo Properties for Folate Receptor Targeting.
MedLine Citation:
PMID:  22372827     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The folate receptor (FR) is upregulated in various cancer types (FR-α isoform) and activated macrophages (FR-β isoform) which are involved in inflammatory and autoimmune diseases, but its expression in healthy tissues and organs is highly restricted to only a few sites (e.g kidneys). Therefore, the FR is a promising target for imaging and therapy of cancer and inflammation using folate-based radiopharmaceuticals. Herein, we report the synthesis and evaluation of a novel folic acid conjugate with improved properties suitable for positron emission tomography (PET). [18F]-fluoro-deoxy-glucose folate ([18F]3) was synthesized based on the click chemistry approach using 2-deoxy-2-[18F]fluoroglucopyranosyl azide and a folate alkyne derivative. The novel radiotracer [18F]3 was produced in good radiochemical yields (25% d.c.) and high specific radioactivity (90 GBq/µmol). Compared to previously published 18F-folic acid derivatives, an increase in hydrophilicity was achieved by using a glucose entity as a prosthetic group. Biodistribution and PET imaging studies in KB tumor-bearing mice showed a high and specific uptake of the radiotracer in FR-positive tumors (10.03 ± 1.12%ID/g, 60 min p.i.) and kidneys (42.94 ± 2.04%ID/g, 60 min p.i.). FR-unspecific accumulation of radioactivity was only found in the liver (9.49 ± 1.13%ID/g, 60 min p.i.) and gallbladder (17.59 ± 7.22%ID/g, 60 min p.i.). No radiometabolites were detected in blood, urine and liver tissue up to 30 min after injection of [18F]3. [18F]-fluoro-deoxy-glucose-folate ([18F]3) is thus a promising PET radioligand for imaging FR-positive tumors.
Authors:
Cindy Fischer; Cristina Müller; Josefine Reber; Adrienne Müller; Stefanie Kraemer; Simon M Ametamey; Roger Schibli
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-29
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  -     ISSN:  1520-4812     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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