[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.

¹⁸F-ФДГ и другие меченые производные глюкозы для использования в радионуклидной диагностике онкологических заболеваний (обзор)

“…Äðóãèì ïðèìåðîì èñïîëüçîâàíèÿ òîðûé âñòóïàåò â ðåàêöèþ ñ ôóíêöèîíàëèçèðîâàííîé ìî-ëåêóëîé ôîëèåâîé êèñëîòû (àëêèí ôîëÿòîì 2) â ïðèñóò-ñòâèè Cu(OAc) 2 (10 mL, 0,1 M) è àñêîðáèíàòà íàòðèÿ (50°C, 15 ìèí) [79].…”

Imaging the Folate Receptor on Cancer Cells with 99mTc-Etarfolatide: Properties, Clinical Use, and Future Potential of Folate Receptor Imaging

“…To date, 18 Ffluorodeoxyglucose-folate and 39-aza-29-18 F-fluorofolic acid seem the most promising PET FR imaging agents. Both have shown good tumor visualization, with limited accumulation in nonmalignant tissues (24,25). 68 Ga-labeled radiofolates are also of interest because of their favorable biodistribution profile and 1-step radiolabeling (26,27).…”

Sweetening Pharmaceutical Radiochemistry by18F-Fluoroglycosylation: A Short Review

“…The 18 F-glycosylation via CuAAC was also transferred to the radiosyntheses of a couple of nonpeptidic compounds [23–29]. For the radiosynthesis of an 18 F-fluoroglycosylated folate derivative by Fischer et al, the intermediate 3,4,6-tri- O -acetyl-2-deoxy-2-[ 18 F]fluoroglucopyranosyl azide 2 was separated by solid phase extraction, excluding the HPLC purification [23].…”