Radiochemistry and Clinical PET Imaging Methods for 18F-THK5351[1-2]
This protocol is adapted from research data and provided for reference only. Adjustments may be necessary based on specific experimental requirements.
1. Radiochemical Synthesis of 18F-THK5351 from THK535:
(1) The target water containing fluorine-18 (18F-), produced by a cyclotron, is passed through a Sep-Pak Light Accell Plus QMA cartridge. The 18F- is captured on the cartridge. It is then eluted into a reaction vial using a Kryptofix solution. The eluate is mixed with acetonitrile, and water is removed by azeotropic distillation to obtain a dry 18F-/Kryptofix 222/K₂CO₃ complex.
(2) THK5352 (3mg, 5.3μmol) dissolved in 0.7mL of DMSO is added to the dry reaction vial. The mixture is stirred at 110°C for 10 minutes. Then, 0.2mL of 2mol/L aqueous HCl is added, and stirring continues at 110°C for another 3 minutes. Subsequently, 1mL of 0.8mol/L aqueous AcOK and 7mL of distilled water are added to quench the reaction.
(3) The product is eluted from a C18 cartridge using 60% ethanol. The ethanolic eluate is mixed with water and then purified by semi-preparative HPLC. Chromatographic conditions: Inertsil ODS-4 column, mobile phase: 20mmol/L NaH₂PO₄ / acetonitrile (75/25, v/v), flow rate: 5.0mL/min. The HPLC fraction corresponding to 18F-THK5351 is collected.
2. PET Imaging Procedure: Intravenously inject a dose of 185MBq of 18F-THK5351. Perform a dynamic PET scan using a PET scanner for 90 minutes. Reconstruct the PET images and calculate standardized uptake value (SUV) images. Co-register the individual's T1-weighted MRI image with the early (0-10 minutes post-injection) PET image. Spatially normalize the co-registered MR and PET images to a template in Talairach space. Manually or semi-automatically place regions of interest (ROIs) on the normalized images. Calculate the ratio of the SUV in each ROI to the SUV in the cerebellar cortex (SUVR) as an index of tracer retention.
Precautions:
(1) Operators must strictly adhere to radiation protection regulations, wear appropriate protective equipment, and perform the final sterile filtration and dispensing of the product under aseptic conditions.
References:
[1] Harada R, Okamura N, Furumoto S, et al. 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease. J Nucl Med. 2016 Feb;57(2):208-14.
[2] Okamura N, Furumoto S, Harada R, et al. Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease. J Nucl Med. 2013 Aug;54(8):1420-7. |
