Radiosynthesis of [18F]SiFAlin-TATE for clinical neuroendocrine tumor positron emission tomography

Abstract

Here, we describe an extension of our silicon fluoride acceptor (SiFA) protocol for ¹⁸F-labeling of peptides that addresses challenges associated with preparing a clinical-grade (Tyr³)-octreotate (TATE) tracer for diagnosis of neuroendocrine tumors (NETs). After several iterations of protocol optimization (e.g., finding the optimal pH at which the isotopic exchange (IE) reaction produces high radiochemical yields (RCYs)), the SiFA technology achieved clinical applicability, as showcased by radiosynthesis of [¹⁸F]SiFAlin-TATE ([¹⁸F]SiTATE), the first SiFA peptide used in the clinical diagnosis of NETs. The TATE peptide binds to somatostatin receptors associated with NETs. Radiolabeled TATE derivatives are routinely applied in clinical oncological PET imaging. The (SiFA) ¹⁸F-labeling technology is based on the IE of a ¹⁹F atom for a radioactive ¹⁸F atom, a highly efficient labeling reaction under mild conditions. The ¹⁹F is part of a biomolecule bearing the SiFA building block, composed of a central silicon (Si) atom, a ¹⁹F atom connected to the Si atom, and two Si-bound tert-butyl groups. The IE proceeds through a penta-coordinate bipyramidal intermediate, followed by elimination of non-radioactive ¹⁹F, yielding the labeled compound in high RCYs at room temperature (22 °C). The simplicity and lack of side-product formation of this approach enable a one-step, kit-like preparation of structurally complex and unprotected radiopharmaceuticals. Compounds such as peptides used for tumor imaging in nuclear medicine can be ¹⁸F-labeled without the need for complex purification protocols. [¹⁸F]SiTATE can be synthesized within 30 min in preparative RCYs of 42%, radiochemical purity of >97% and high molar activity of 60 GBq/µmol.