Application of fluorine-18 in the syntheses of PET radiotracers

Positron emission tomography (PET) is a nuclear medicine imaging technique that uses physiologically active compounds labelled with positron-emitting radionuclides to image and measure the function of in vivo biological processes with minimal disturbance. Fluorine-18 ( ¹⁸F; 97% β ⁺, E max = 0.635 MeV, t 1/2 = 109.7 min) is the most commonly used radionuclide in PET. At McMaster University, ¹⁸F has been produced by the use of a reactor ( ⁶Li(n,α) ³H; ¹⁶O(t,n) ¹⁸F)), a tandem Van de Graaf accelerator ( ²⁰Ne(d,α) ¹⁸F) and a negative ion proton cyclotron. Neither the reactor nor the accelerator is suitable for the production of ¹⁸F for clinical use because of the co-production of tritium (reactor) and low ¹⁸F yield (accelerator). Presently, a Siemens RDS 112 proton cyclotron operating at 11 MeV is used for the routine production of ¹⁸F by the nuclear reaction, ¹⁸O(p,n) ¹⁸F. The present study focuses on the radiofluorination of the carbon-carbon double bond in 3,4,6-tri-O-acetyl-D-glucal (TAG) by ¹⁸F labelled F 2 ([ ¹⁸F]F 2) to produce 2-[ ¹⁸F]fluoro-2-deoxy-D-glucose (2-FDG) and 2-[ ¹⁸F]fluoro-2- deoxy-β-D-allose (2-FDβA). 2-[ ¹⁸F]fluoro-2-deoxy-D-glucose has proven to be an invaluable probe for the study of local glucose metabolism in humans when used in conjunction with PET and has become the standard PET imaging agent against which other imaging agents for tumor detection are compared. 2-[ ¹⁸F]fluoro-2-deoxy-β-D-allose is an analogue of the rare sugar, D-allose. It has been suggested that D-allose may be useful for the treatment of ischemia/reperfusion injury and leukemia.