[18F]Fluoro-Deoxy-Glucose Folate: A Novel PET Radiotracer with Improved in Vivo Properties for Folate Receptor Targeting
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- 作者：Cindy R. Fischer ; Cristina M眉ller ; Josefine Reber ; Adrienne M眉ller ; Stefanie D. Kr盲mer ; Simon M. Ametamey ; Roger Schibli
- 刊名：Bioconjugate Chemistry
- 出版年：2012
- 出版时间：April 18, 2012
- 年：2012
- 卷：23
- 期：4
- 页码：805-813
- 全文大小：326K
- 年卷期：v.23,no.4(April 18, 2012)
- ISSN：1520-4812
文摘
The folate receptor (FR) is upregulated in various cancer types (FR-伪 isoform) and in activated macrophages (FR-尾 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/渭mol). 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 卤 1.12%ID/g, 60 min p.i.) and kidneys (42.94 卤 2.04%ID/g, 60 min p.i.). FR-unspecific accumulation of radioactivity was only found in the liver (9.49 卤 1.13%ID/g, 60 min p.i.) and gallbladder (17.59 卤 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.
[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/渭mol). 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 卤 1.12%ID/g, 60 min p.i.) and kidneys (42.94 卤 2.04%ID/g, 60 min p.i.). FR-unspecific accumulation of radioactivity was only found in the liver (9.49 卤 1.13%ID/g, 60 min p.i.) and gallbladder (17.59 卤 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.