Chemistry for Positron Emission Tomography: Recent Advances in ¹¹C‐, ¹⁸F‐, ¹³N‐, and ¹⁵O‐Labeling Reactions

Abstract

Positron emission tomography (PET) is a molecular imaging technology that provides quantitative information about function and metabolism in biological processes in vivo for disease diagnosis and therapy assessment. The broad application and rapid advances of PET has led to an increased demand for new radiochemical methods to synthesize highly specific molecules bearing positron-emitting radionuclides. This article provides an overview of commonly-used labeling chemistry in the examples of clinically relevant PET tracers, and highlights most recent development and breakthroughs over the past decade with focus on 11C, 18F, 13N, and 15O.

Synthesis and Preliminary Evaluation of [11C]GNE‐1023 as a Potent PET Probe for Imaging Leucine‐Rich Repeat Kinase 2 (LRRK2) in Parkinson's Disease

“…[17,18] In the last decade, several LRRK2 inhibitors, including GNE-1023, GNE-7915, GNE-0877, GNE-9605, PF-06447475, and MLi-2 have been reported ( Figure 1). [25] As an oninvasive and highly sensitive molecular imaging tool, PET has been widely used to probe in vivo biological processes under normalo rd isease conditions. [24] Particularlyn otable is that GNE-1023 contains ap henolic methyl group, which would allow facile labeling with carbon-11f or positrone mission tomography (PET) imaging studies.…”

“…[24] Particularlyn otable is that GNE-1023 contains ap henolic methyl group, which would allow facile labeling with carbon-11f or positrone mission tomography (PET) imaging studies. [25] As an oninvasive and highly sensitive molecular imaging tool, PET has been widely used to probe in vivo biological processes under normalo rd isease conditions. [26][27][28] PET studies of LRRK2 would enableadeeper understanding of PD and other LRRK2-related disorders, as well as help to validatea nd translate novel LRRK2 inhibitors.…”

Automated microfluidic chip system for radiosynthesis of PET imaging probes

“…Positron emission tomography (PET) is a powerful non-invasive molecular imaging technique for the early detection, characterization, and "real-time" monitoring of disease, and for investigating the efficacy of drugs (Phelps, 2000;Ametamey et al, 2008). The development of molecular probes bearing shortlived positron-emitting radionuclides, such as 18 F (half-life 110 min) or 11 C (half-life 20 min), is crucial for PET imaging to collect in vivo metabolic information in a time-efficient manner (Deng et al, 2019). In this regard, one of the main challenges is rapid synthesis of radiolabeled probes by introducing the radionuclides into pharmaceuticals as soon as possible before injection for a PET scan.…”

Synthesis and Preliminary Evaluation of 11C‐Labeled VU0467485/AZ13713945 and Its Analogues for Imaging Muscarinic Acetylcholine Receptor Subtype 4

“…[45] The synthon [ 11 C]CH 3 Iw as transferred into ap re-cooled (À15 to À20 8C) reactionv essel containing precursor 12 a-c, NaOH anda nhydrous DMF.A fter the radioactivity was delivered, the reactionv essel wasw armed to 80 8Ca nd maintained for 5min. [45] The synthon [ 11 C]CH 3 Iw as transferred into ap re-cooled (À15 to À20 8C) reactionv essel containing precursor 12 a-c, NaOH anda nhydrous DMF.A fter the radioactivity was delivered, the reactionv essel wasw armed to 80 8Ca nd maintained for 5min.…”

“…As shown in Scheme 2, the methyle ther of M 4 RP AMs was identified as the most accessible labeling site with carbon-11. [45] The synthon [ 11 C]CH 3 Iw as transferred into ap re-cooled (À15 to À20 8C) reactionv essel containing precursor 12 a-c, NaOH anda nhydrous DMF.A fter the radioactivity was delivered, the reactionv essel wasw armed to 80 8Ca nd maintained for 5min. The reaction mixture was purified by semi-prep radio-HPLC, and reformulatedi nasaline solution( 3mL) containing 100 mLo f2 5% ascorbic acid in sterile water and1 00 mL of 20 %T ween 80 in ethanol.…”