Journal Article

Radiosynthesis of 18FSiFAlin-TATE for clinical neuroendocrine tumor positron emission tomography

Wängler, Carmen, Schirrmacher, Ralf, Jurkschat, Klaus, Bailey, Justin J., Wängler, Björn, Lindner, Simon, Bartenstein, Peter

2020

Overview

Here, we describe an extension of our silicon fluoride acceptor (SiFA) protocol for 18 F-labeling of peptides that addresses challenges associated with preparing a clinical-grade (Tyr 3 )-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 [ 18 F]SiFA lin- TATE ([ 18 F]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) 18 F-labeling technology is based on the IE of a 19 F atom for a radioactive 18 F atom, a highly efficient labeling reaction under mild conditions. The 19 F is part of a biomolecule bearing the SiFA building block, composed of a central silicon (Si) atom, a 19 F 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 19 F, 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 18 F-labeled without the need for complex purification protocols. [ 18 F]SiTATE can be synthesized within 30 min in preparative RCYs of 42%, radiochemical purity of >97% and high molar activity of 60 GBq/µmol. This extension of the original silicon fluoride acceptor (SiFA) protocol for 18 F-labeling of peptides describes modifications required for the preparation of clinical-grade [ 18 F]SiFA lin -TATE for diagnosis of neuroendocrine tumors via PET imaging.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/1647/245/2092 / 631/92/2783 / 639/638/549 / 692/4028/67/2322 / 692/53/2421 / Affinity labeling / Analytical Chemistry / Biological Techniques / Biomedical and Life Sciences / Biomolecules / Chemistry Techniques, Synthetic / Computational Biology/Bioinformatics / Diagnosis / Fluorides / Fluorides - chemical synthesis / Fluorides - chemistry / Fluorine isotopes / Fluorine Radioisotopes - chemistry / Humans / Isotope Labeling / Labeling / Life Sciences / Medical imaging / Methods / Microarrays / Neuroendocrine tumors / Neuroendocrine Tumors - diagnostic imaging / Nuclear medicine / Optimization / Organic Chemistry / Peptides / Peptides, Cyclic - chemistry / PET imaging / Positron emission / Positron emission tomography / Production processes / Protocol / Protocol Extension / Radioactive tracers / Radiochemistry / Radiochemistry - methods / Radiopharmaceuticals / Room temperature / Silicon / Silicon Compounds - chemical synthesis / Silicon Compounds - chemistry / Somatostatin / Somatostatin receptors / Tomography / Tumors