Synthesis and evaluation of novel potent TSPO PET ligands with 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide

A Systematic Review on Dementia and Translocator Protein (TSPO): When Nuclear Medicine Highlights an Underlying Expression

“…Pike et al synthesized a library of new 2-phenylindol-3-ylglyoxylamide derivatives of the general formula II (compounds 19 – 31 ), attributing a methyl group on the indole nitrogen. Then, they tested ligand 31 ( Figure 7 ) which, thanks to its methyl group, was feasible to label with carbon-11 for positron emission tomography (PET) imaging in monkeys [ 30 ]. Peak radioactivity was observed in a region rich in TSPO 40 min after tracer injection, with a maximal accumulation in putamen between 12 and 32 min.…”

Recent progress on radiofluorination using metals: strategies for generation of C–18F bonds

“…Therefore, PET has been widely used in the diagnosis, monitoring, and treatment of various diseases including cancers, cardiological diseases, and chronic inflammatory diseases. [35][36][37][38][39][40][41][42][43][44][45][46] In particular, the PET strategy has proved effective in clinical applications to treat diseases related to the central nervous system, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and psychiatric disorders. [47][48][49][50][51][52][53][54][55][56][57][58] Over the past several decades, the PET technique has demonstrated a significant role in the field of medicine and has significantly increased in popularity.…”

TSPO imaging in animal models of brain diseases

“… Human 3h First in a human demonstration that a systemic LPS challenge induces microglial activation in the brain [ 25 , 46 ] [ 11 C]-R-PK11195 Model of maternal infection as a risk factor for periventricular leukomalacia and cerebral palsy (CP) in neonates Intra-uterine exposure in pregnant rabbits (20 μg/kg) Rabbit 1–7 days post-injection Increased TSPO-PET in the brain and increased inflammatory markers are detected up to 2 weeks after birth [ 47 ] [ 18 F]DPA-713 To evaluate if TSPO-TEP reveals specifically the pro- or anti-inflammatory phenotype Cultured rodent astrocytes, microglia and macrophages stimulated with TNF, LPS and IL-4; mice injected with AdTNF or IL-4 Mice TSPO expression corresponds to a pro-inflammatory phenotype [ 33 ] [ 123 I]CLINDE Determine the cell population in which TSPO is altered using fluorescence-activated cell sorting on radioligand-treated tissue Intracerebral (hippocampus) (10 μg) Rat 3 days post-injection LPS induces a microglial expansion and an increase in microglial TSPO binding [ 30 ] [ 11 C]-R-PK11195, [ 11 C]DAA1106, [ 11 C]PBR28, [ 18 F]DPA-714, [ 18 F]GE-180, [ 18 F]fluoromethyl-PBR28 Validation and comparison of TSPO-PET ligands; validation of pharmacokinetic quantification models Intracerebral (striatum) (1 μg, 10 μg, 50 μg) Rat 3–4 days post-injection/longitudinal after injection 2nd generation TSPO ligands reveal a higher uptake compared to that of [ 11 C]-R-PK11195. IHC characterization of the LPS model [ 40 , 35 , 38 , 44 , 39 , 48 – 51 , 34 , 52 ] [ 18 F]CB251 Comparison and validation of a new 3rd generation TSPO ligand; characterization and identification of immune cells contributing to LPS-induced neuroinflammation …”