Positron Emission Tomography

Radiochemistry is a specialized branch of chemistry that incorporates radioisotopes such as fluorine-18 (18F), carbon-11 (11C), and oxygen-15 (15O) into biologically active molecules to create radiotracers for imaging. Once injected into the patient, radiotracers emit positrons, which are positively charged electrons, which enable positron emission tomography (PET). PET is a powerful and non-invasive imaging technique used in both clinical and research settings that allows for the in-vivo visualization and measurement of metabolic and biochemical processes in the human body.

Symeres has long-standing expertise in the design and synthesis of a wide variety of precursors to be used for positron emission tomography. When synthesizing a radiochemical, initially the synthetic sequence is validated on ­cold material before the route is transferred to a radiolab where  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, but not limited to, specificity and affinity for the target, stability/metabolism, molar activity (specific activity), clearance from the blood, and lipophilicity should be considered. Due to 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 the last or penultimate step of the synthetic sequence. 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 technical know-how. This cooperation between UMCG and Symeres 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].

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 experts to learn more about our PET capabilitites!

[1] S. Van der Hoek et al., Clin. Pharmacol. Ther. 2022, 6 , 1264-1270 DOI: https://doi.org/10.1002/cpt.2744

[2] S. Van der Hoek et al., J. Med. Chem. 2021, 64 , 16641–16649 DOI: https://doi.org/10.1021/acs.jmedchem.1c01269

[3] T. Läppchen et al., Eur. J. Med. Chem. 2015, 89 , 279–295 DOI: https://doi.org/10.1016/j.ejmech.2014.10.048

[4] V.I. Böhmer et al., Chem. Eur. J. 2020, 27 , 6993 DOI: https://doi.org/10.1002/chem.202001795

[5] N. Ghazanfari et al., Mol. Pharmaceutics 2022, 19 , 2287–2298 DOI: https://doi.org/10.1021/acs.molpharmaceut.2c00121

[6] N. Ghazanfari et al., Mol. Pharmaceutics 2022, 19 , 918–928 DOI: https://doi.org/10.1021/acs.molpharmaceut.1c008891

[7] L. Garcia-Varela et al., EJNMMI Radiopharmacy and Chemistry 2021, 6, DOI: https://doi.org/10.1186/s41181-021-00139-8/a>

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