High-Yielding Aqueous ¹⁸F-Labeling of Peptides via Al¹⁸F Chelation

Abstract

The coordination chemistry of a new pentadentate bifunctional chelator (BFC), NODA-MPAA 1, containing the 1,4,7-triazacyclononane-1,4-diacetate (NODA) motif with a methyl phenyl acetic acid (MPAA) backbone, and its ability to form stable Al18F-chelates, was investigated. The organofluoroaluminates were easily accessible from the reaction of 1 and AlF3. X-ray diffraction studies revealed aluminum at the center of a slightly distorted octahedron, with fluorine occupying one of the axial positions. The tert-butyl protected prochelator 7, which can be synthesized in one step, is useful for coupling to biomolecules on solid phase or in solution. High yield (55–89%) aqueous 18F-labeling was achieved in 10–15 minutes with a tumor-targeting peptide 4 covalently linked to 1. Defluorination was not observed for at least 4 h in human serum at 37 °C. These results demonstrate the facile application of Al18F chelation using BFC 1 as a versatile labeling method for radiofluorinating other heat-stable peptides for positron emission imaging.

Preclinical Comparison of Al18F- and 68Ga-Labeled Gastrin-Releasing Peptide Receptor Antagonists for PET Imaging of Prostate Cancer

“…This novel technique has been successfully applied to several peptides, including a GRPR agonist (28) and recently to GRPR antagonists (31,32). Recently, McBride et al reported the labeling of peptides with Al 18 F in a 1-pot, 1-step procedure using the NODA-MPAA chelator (26,33), leading to a kit formulation, after which the labeled peptide could be purified by solid-phase extraction.…”

“…JMV5132 was synthesized in the same manner as JMV4168 but was coupled to tert-butyl (tBu)-protected NODA-MPAA instead of tBu-protected DOTA. NODA-MPAA was prepared as previously described using NO2AtBu (Chematech) (26). The chemical structures of JMV4168 and JMV5132 are shown in Figure 1.…”

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

“…As shown previously, NOTA-conjugated peptides can be labeled with 18 F using the Al 18 F method (17)(18)(19). Here, we describe the 18 F labeling of NOTA-8-Aoc-BBN(7-14)NH 2 , using the new 1-pot, 1-step, labeling method.…”