Synthesis and radiolabelling of a Radiofluorinated PET Imaging Probe Based on PIB and THK523

Objectives To develop PIB and THK523 based molecular probe for imaging in vivo both amyloid deposits and NFTs.

Methods Standard reference THKP and precursor TKP were designed and synthesized. [¹⁸F]-TKP was automatically synthesized using one pot and two-pot reaction. Labelling yields, synthesis time and the specific activity of [¹⁸F]-TKP were compared. Biodistribution in brains were evaluated.

Results The radiochemical purity of [¹⁸F]-TKP was greater than 95%. The radiolabelling yield of [¹⁸F]-TKP was obtained in a range of 18 ± 3% (n=6, one pot) and 25 ± 5% (n=6, two-pot). The total synthesis time of [¹⁸F]-TKP were 45-55 min and 55-70 min and the specific activities were 0.7 ± 0.2 Ci/µmol and 1.5 ± 0.2 Ci/µmol at the end of synthesis for one pot and two pot reaction, respectively (decay corrected to EOB). Biodistribution of [¹⁸F]-TKP displayed high brain permeability at early time point. At later points, [¹⁸F]-TKP was cleared rapidly from wild-type rat brains, indicating low non-specific binding in vivo. Small molecular probe [¹⁸F]-TKP has been developed that readily entered the brain.

Conclusions In summary, we reported here the design, synthesis, and evaluation of a novel imaging probe [¹⁸F]-TKP based on the major component of THK523 and PIB. [¹⁸F]-TKP can be labeled with ¹⁸F by using one-pot and two-pot reaction. The two-pot reaction is preferred because the high yield and specific activity can be achieved. In addition, in vivo microPET study of [¹⁸F]-TKP in normal rats showed a good initial brain penetration and rapid washout from the brain. These studies suggested that [¹⁸F]-TKP could be easily performed on an automated synthesis module for routine production of high yield and might be a useful PET radiotracer for AD imaging but awaits further evaluation in animal models of AD disease.

Research Support National Natural Science Foundation of China (Nos. 81271516 and 81371625), Program of Shanghai Science and Technology Commission (Nos. 13JC1401503 and 14DZ1930402), Fudan University and Shanghai Municipal Health and Family Planning Commission (Project No: 2013313).