Positron Emission Tomography at Symeres

Symeres has long-standing expertise in the design and synthesis of a wide variety of precursors to be used for positron emission tomography (PET), a medical imaging technique that enables visualization of in vivo biological mechanisms in a noninvasive way. Precursors are subsequently labeled with a positron-emitting radionuclide by a Symeres radiochemist, who is trained and qualified to work with radiochemicals.

To make a tracer an ideal PET candidate, aspects such as specificity and affinity for the target, stability/metabolism, molar activity (specific activity), clearance from the blood, and lipophilicity are only a few of those that should be considered. Because of the short physical half-lives of the isotopes used (e.g., 18F: 110 min, 11C: 20 min), the preparation and purification of a PET radiopharmaceutical must be performed very rapidly. Ideally, precursors should be modified in such a way that the radiolabel can be incorporated in (one of) the last synthetic step(s). Purification of the tracer is immediately performed after radiosynthesis, often on a reversed-phase (semi)preparative HPLC system equipped with UV and radioactivity detectors. After formulation, sterilization, and administration, the tracers can be used in PET scanning procedures to visualize biological processes related to the compound (e.g., metabolism, biodistribution, kinetics, enzymatic activity, receptor occupancy) for disease diagnosis and treatment (theranostics), or to aid the drug-discovery process.

Synthesis of the precursors is carried out in the Symeres labs, and labeling is performed at the radiochemistry (GMP) labs of the University Medical Centre of Groningen (UMCG), utilizing their cyclotron, PET cameras, and know-how. This cooperation between UMCG and Symeres is now also offered as a combined service to the pharmaceutical industry. Our on-going research on diabetes[1][2] provides an excellent example of this unique cooperation. A new route (7 synthetic steps) towards a precursor of canagliflozin has been developed (Scheme 1). Radiolabeling of the precursor was explored and subsequently implemented in the GMP labs of UMCG. Currently, clinical studies are being performed on patients with diabetes[2].

canagliflozin labeling Symeres
Scheme 1: Labeling of canagliflozin precursor with 18F.

Other examples of precursors and tracers produced for our clients are antitumor agents[3] to study prostate cancer[4], non-small-cell lung cancer, and refractory solid tumors. Furthermore, tracers were prepared to study Parkinson’s disease[5][6], inflammatory bowel disease, and P-glycoprotein function[7].

Please contact our expert directly to learn more about our PET capabilitites!

[1] Van der Hoek, S. et. al., Studying Telmisartan Plasma Exposure, Kidney Distribution, Receptor Occupancy and Response in Patients with Type 2 Diabetes Using [11C]Telmisartan, Clin. Pharmacol. Ther., 2022, 6, 1264-1270, Link

[2] Van der Hoek, S. et. al., GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium–Glucose Cotransporter 2, J. Med. Chem., 2021, 64, 16641–16649, Link

[3] Läppchen, T. et. al., Novel Analogs of Antitumor Agent Calixarene 0118: Synthesis, Cytotoxicity, Click Labeling with 2-[18F]Fluoroethylazide, and In Vivo Evaluation, Eur. J. Med. Chem., 2015, 89, 279–295, Link

[4] Böhmer, V.I. et. al., Modular Medical Imaging Agents Based on Azide–Alkyne Huisgen Cycloadditions: Synthesis and Pre-Clinical Evaluation of 18F-Labeled PSMA-Tracers for Prostate Cancer Imaging, Chem. Eur. J., 2020, 27, 6993, Link

[5] Ghazanfari, N. et. al., Binding of the Dual-Action Anti-Parkinsonian Drug AG-0029 to Dopamine D2 and Histamine H3 Receptors: A PET Study in Healthy Rats, Mol. Pharmaceutics 2022, 19, 2287–2298, Link

[6] Ghazanfari, N. et. al., Pharmacokinetic Modeling of [11C]GSK-189254, PET Tracer Targeting H3 Receptors, in Rat Brain, Mol. Pharmaceutics 2022, 19, 918–928, Link

[7] Garcia-Varela, L. et. al., A New Approach to Produce [18F]MC225 via One-Step Synthesis, a PET Radiotracer for Measuring P-gp Function, EJNMMI Radiopharmacy and Chemistry 2021, 6, 24, Link



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