Fluorine-18 Patents (2009–2015). Part 2: New Radiochemistry

Abstract

Fluorine-18 ((18)F) is one of the most common positron-emitting radionuclides used in the synthesis of positron emission tomography radiotracers due to its ready availability, convenient half-life and outstanding imaging properties. In Part 1 of this review, we presented the first analysis of patents issued for novel radiotracers labeled with fluorine-18. In Part 2, we follow-up with a focus on patents issued for new radiochemistry methodology using fluorine-18 issued between January 2009 and December 2015.

Diaryliodoniums Salts as Coupling Partners for Transition-Metal Catalyzed C- and N-Arylation of Heteroarenes

“…Diaryliodonium salts appear as fairly appealing electrophilic arylating reagents as well as precursors for positron emission tomography (PET) [39,40]. They are powerful intermediates for the synthesis of a broad range of radiofluorinated synthons and clinically relevant PET tracers [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]. Since the pioneering works on the palladium-and copper-catalyzed arylation of sp2 C-H indoles reported respectively by Sanford [57] and Gaunt groups [58], Nand C-arylation involving diaryliodonium salts offer a highly complementary strategy for the synthesis and derivatization of heteroarenes (Scheme 1).…”

Radiochemistry for positron emission tomography

“…However, the rapid growth in nuclear medicine and drug discovery for radiopharmaceuticals poses inherent challenges to radiochemists, since the radiolabeling of many biologically relevant compounds remains difficult. As such, strenuous efforts have been devoted to the development of new radiosynthetic strategies, including the progress from the patents [259][260][261][262] . Over the past decade, these efforts provided a plethora of novel synthetic options and broadened the scope of functional groups that can be harnessed for radiolabeling.…”

Carbon-11 and Fluorine-18 Labeled Amino Acid Tracers for Positron Emission Tomography Imaging of Tumors

“…Tumor cell accumulation of AA PET tracers mainly depends on the rate and mechanism of AAs transport. Based on the over-expression of AA transporters, the uptake of AA PET tracers in tumor cells is greater than that in normal cells (Mossine et al, 2016 ).…”

“…Most AA PET tracers are labeled with positron radionuclides 11 C and 18 F. Theoretically, almost all AAs be labeled with 11 C, however, their short half-life (20 min, 100% of beta positron decay) is not suitable for delayed PET imaging. To overcome this shortcoming of 11 C and to facilitate the utility of AA PET tracers in hospitals without on-site cyclotron and labeling equipment, a series of 18 F labeled AAs (half-life of 110 min, 97% of beta positron decay) were developed (Mossine et al, 2016 ). Based on that AAs have a common molecular formula [R-CH-(NH 2 )-COOH], with a carboxylic acid group (-COOH), an amino group (-NH 2 ) linking to the alpha-carbon atom (-CH-), and branched-chain group (-R).…”