New approaches for direct labeling of temperature-sensitive molecules with [¹⁸F]AlF

Objectives We developed a one-step method of labeling molecules with ¹⁸F by mixing ¹⁸F^- in saline with Al³⁺ and a molecule containing a 1,4,7-triazacyclononane-1,4-diacetate derivative (NODA or NOTA). Incubations at elevated temperatures (100°C) and a co-solvent, such as ethanol, are used to optimize radiolabeling yields. Many molecules can tolerate these labeling conditions but some are heat-sensitive and may precipitate or denature if the concentration of a co-solvent is too high. We previously reported a variety of 2-step procedures that could be used effectively with small molecules and proteins; however, we also are examining other derivatives that may be suitable for one-step labeling of temperature-sensitive compounds.

Methods New NODA derivatives with different functional groups in the vicinity of the 1,4,7-triazacyclononane ring were prepared and attached to a standard test peptide. The peptides were radiolabeled over a range of temperatures from 50 to110°C with and without a co-solvent.

Results Two of the new ligand derivatives containing a pyridyl (IMP508) or a triazole (IMP517) group showed improved labeling yields at lower temperatures as well as labeling equal or better than the benzyl-NODA (IMP485) standard at higher temperatures. Adding ethanol to the triazole derivative did not increase yields as much as the other derivatives, indicating that it may be possible to improve the radiolabeling yield at lower temperatures and reduce or eliminate the need for a co-solvent.

Conclusions Alterations to the NODA/NOTA ligand on a peptide can have a positive effect on the radiolabeling yield of the peptide, and may lead to ligands that can be used for direct one-step ¹⁸F labeling of some temperature-sensitive molecules.

Research Support This project was supported in part by the National Center for Research Resources and the National Institute of Biomedical Imaging and Bioengineering of the NIH through grant # 5R44RR028018-03.