Improved ¹⁸F Labeling of Peptides with a Fluoride-Aluminum-Chelate Complex

Abstract

We reported previously the feasibility to radiolabel peptides with fluorine-18 (18F) using a rapid, one-pot, method that first mixes 18F− with Al3+, and then binds the (Al18F)2+ complex to a NOTA ligand on the peptide. In this report, we examined several new NOTA ligands and determined how temperature, reaction time, and reagent concentration affected the radiolabeling yield. Four structural variations of the NOTA ligand had isolated radiolabeling yields ranging from 5.8% to 87% under similar reaction conditions. All of the Al18F NOTA complexes were stable in vitro in human serum and those that were tested in vivo also were stable. The radiolabeling reactions were performed at 100°C and the peptides could be labeled in as little as five minutes. The IMP467 peptide could be labeled up to 115 GBq/μmol (3100 Ci/mmol), with a total reaction and purification time of 30 min without chromatographic purification.

Imaging of Human Epidermal Growth Factor Receptor Type 2 Expression with 18F-Labeled Affibody Molecule ZHER2:2395 in a Mouse Model for Ovarian Cancer

“…This process requires a long synthesis time of approximately 2 h. We were able to radiolabel Affibody molecules with 18 F within 30 min using a 2-step, 1-pot reaction. In addition, in future studies the specific activity of 18 F-NOTA-Z HER2:2395 may be improved by using different chelators and solvents (29,30).…”

PET of Tumors Expressing Gastrin-Releasing Peptide Receptor with an 18F-Labeled Bombesin Analog

“…We also had to purify our 18 F-labeled peptide with HPLC to obtain a high-specific-activity preparation. Recently, McBride et al have shown that the AlF method can be further optimized using other chelators (19,29). They developed a 1-pot method that provides a high labeling efficiency and specific activity with no more than only solid-phase extraction purification needed before formulation for injection.…”

Assessing Antibody Pharmacokinetics in Mice with In Vivo Imaging

“…18 F. A variety of methods to label proteins with 18 F have been described previously (Guhlke et al, 1994;Cai et al, 2008;McBride et al, 2010); however, labeling with this particular isotope generally remains a challenge because of its short half-life, low radiochemical yields, and low specific activities. A commonly used approach uses the 18 F-labeled amine-reactive intermediate N-succinimidyl 4-[…”

“…This approach involves the 18 F-labeling of the intermediate followed by conjugation to the protein. An approach using a bifunctional chelate has also been described previously (McBride et al, 2009(McBride et al, , 2010.…”