[18F]fluoro-deoxy-glucose folate: a novel PET radiotracer with improved in vivo properties for folate receptor targeting.

Abstract

The folate receptor (FR) is upregulated in various cancer types (FR-α isoform) and in 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). [(18)F]-fluoro-deoxy-glucose folate ([(18)F]3) was synthesized based on the click chemistry approach using 2-deoxy-2-[(18)F]fluoroglucopyranosyl azide and a folate alkyne derivative. The novel radiotracer [(18)F]3 was produced in good radiochemical yields (25% d.c.) and high specific radioactivity (90 GBq/μmol). Compared to previously published (18)F-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 [(18)F]3. [(18)F]-fluoro-deoxy-glucose-folate ([(18)F]3) is thus a promising PET radioligand for imaging FR-positive tumors.

• Authors: Cindy R Fischer, Cristina Müller, Josefine Reber, Adrienne Müller, Stefanie D Krämer, Simon M Ametamey, Roger Schibli
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 23 Issue 4 Pg. 805-13 (Apr 18 2012) ISSN: 1520-4812 [Electronic] United States
• PMID: 22372827 (Publication Type: Journal Article)
• Copyright: © 2012 American Chemical Society

Chemical References

• (18F)fluoro-deoxy-glucose folate
• Alkynes
• Folate Receptor 1
• Folate Receptor 2
• Monosaccharides
• Radioactive Tracers
• Folic Acid

Topics

• Alkynes (chemistry)
• Animals
• Cell Transformation, Neoplastic
• Click Chemistry
• Female
• Folate Receptor 1 (metabolism)
• Folate Receptor 2 (metabolism)
• Folic Acid (analogs & derivatives, chemistry, metabolism, pharmacokinetics)
• Humans
• Hydrophobic and Hydrophilic Interactions
• KB Cells
• Mice
• Monosaccharides (chemistry, metabolism, pharmacokinetics)
• Positron-Emission Tomography (methods)
• Protein Binding
• Radioactive Tracers
• Radiochemistry
• Uterine Cervical Neoplasms (diagnostic imaging, metabolism, pathology)