Cu‐mediated radiofluorination is a versatile tool for the preparation of ¹⁸F‐labeled (hetero)aromatics. In this work, we systematically evaluated a series of complexes and identified several generally applicable mediators for highly efficient radiofluorination of aryl boronic and stannyl substrates. Utilization of these mediators in nBuOH/DMI or DMI significantly improved ¹⁸F‐labeling yields despite use of lower precursor amounts. Impressively, application of 2.5 μmol aryl boronic acids was sufficient to achieve ¹⁸F‐labeling yields of up to 75 %. The practicality of the novel mediators was demonstrated by efficient production of five PET‐tracers and transfer of the method to an automated radiosynthesis module. In addition, (S)‐3‐[¹⁸F]FPhe and 6‐[¹⁸F]FDOPA were prepared in activity yields of 23±1 % and 30±3 % using only 2.5 μmol of the corresponding boronic acid or trimethylstannyl precursor.

Purpose: The preclinical evaluation of 3-l- and 3-d-[¹⁸F]FPhe in comparison to [¹⁸F]FET, an established tracer for tumor imaging. Methods: In vitro studies were conducted with MCF-7, PC-3, and U87 MG human tumor cell lines. In vivo µPET studies were conducted in healthy rats with/without the inhibition of peripheral aromatic l-amino acid decarboxylase by benserazide pretreatment (n = 3 each), in mice bearing subcutaneous MCF-7 or PC-3 tumor xenografts (n = 10), and in rats bearing orthotopic U87 MG tumor xenografts (n = 14). Tracer accumulation was quantified by SUV_max, SUV_mean and tumor-to-brain ratios (TBrR). Results: The uptake of 3-l-[¹⁸F]FPhe in MCF-7 and PC-3 cells was significantly higher relative to [¹⁸F]FET. The uptake of all three tracers was significantly reduced by the suppression of amino acid transport systems L or ASC. 3-l-[¹⁸F]FPhe but not 3-d-[¹⁸F]FPhe exhibited protein incorporation. In benserazide-treated healthy rats, brain uptake after 42–120 min was significantly higher for 3-d-[¹⁸F]FPhe vs. 3-l-[¹⁸F]FPhe. [¹⁸F]FET showed significantly higher uptake into subcutaneous MCF-7 tumors (52–60 min p.i.), while early uptake into orthotopic U87 MG tumors was significantly higher for 3-l-[¹⁸F]FPhe (SUV_max: 3-l-[¹⁸F]FPhe, 107.6 ± 11.3; 3-d-[¹⁸F]FPhe, 86.0 ± 4.3; [¹⁸F]FET, 90.2 ± 7.7). Increased tumoral expression of LAT1 and ASCT2 was confirmed immunohistologically. Conclusion: Both novel tracers enable accurate tumor delineation with an imaging quality comparable to [¹⁸F]FET.

The BrainPET-7T insert is designed for simultaneous human-brain PET imaging with ultra-high-field MRI. It offers a high sensitivity and signal-to-noise ratio by detector blocks of pixelated LSO scintillators with a height of 2.4cm, digital silicon photomultiplier readout, and enhanced data processing methods. This makes it particulary interesting for +--emitter applications, such as dual-isotope imaging, which rely on the detection of triple coincidences. We investigated the scanner sensitivity using the isotopes 124I and 22Na, in comparison to 18F. Count rate performance was assessed using 124I and 18F for different energy window settings with an analysis following the NEMA NU 2-2018 protocol. For the count rate determination, an adapted strategy for estimating the scatter fraction for +--emitters was applied. The peak double coincidence sensitivity for 18F measured at the center and off-center was between 10.16(8)% and 12.37(10)% for energy windows of 440 to 594keV and 420 to 650keV. The true triple sensitivities obtained at the isocenter were 3.13(9)% and 4.88(12)% for 124I and between 0.8662(23)% and 3.112(5)% for 22Na depending on the selected energy window and rejection rule. The maximum RNEC of the 18F-measurement was 276kcps at 16.3kBqmL-1, while the maximum Rtrue was 780kcps at 22.7kBqmL-1 for an energy window of 440 to 594keV. The scatter fraction ranged from 28% to 33% and the random fraction from 3% to 40%. In the case of 124I, the ratio of estimated true triples to doubles was ≈6%, with a higher random fraction of 27% for triples compared to 2.8% for doubles. These results demonstrate the potential feasibility of employing the BrainPET-7T insert for +--emitter applications.