A promising carbon-11-labeled sphingosine-1-phosphate receptor 1-specific PET tracer for imaging vascular injury

Abstract

This preliminary study supports the potential use of PET for quantification of the S1PR1 expression as a biomarker of neointimal hyperplasia.

PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis

“…The radiotracer [ 11 C]TZ3321 was produced as reported recently by our group [21]. Briefly, the radiosynthesis of [ 11 C]TZ3321 was accomplished by alkylating the precursor with [ 11 C]methyl triflate in acetonitrile at 60 °C for 5 min, followed by removal of the t-butyl group using trifluoroacetic acid, and was purified using reverse phase high-performance liquid chromatography (HPLC).…”

“…Currently, the implementation of PET imaging modality for S1PR1 target is hampered due to lack of a suitable specific S1PR1 radiotracer. Our group previously reported the radiosynthesis of [ 11 C]TZ3321 and in vivo evaluation in a mouse model of neointimal hyperplasia [21]. TZ3321 has a highly binding potency for S1PR1 (IC 50 = 2.13 ± 1.63 nM) and does not bind to S1PR2 (IC 50 > 1000 nM) or S1PR3 (IC 50 > 1000 nM); the uptake of [ 11 C]TZ3321 correlated well with inflammatory response at the site of neointimal hyperplasia [21].…”

“…Our group previously reported the radiosynthesis of [ 11 C]TZ3321 and in vivo evaluation in a mouse model of neointimal hyperplasia [21]. TZ3321 has a highly binding potency for S1PR1 (IC 50 = 2.13 ± 1.63 nM) and does not bind to S1PR2 (IC 50 > 1000 nM) or S1PR3 (IC 50 > 1000 nM); the uptake of [ 11 C]TZ3321 correlated well with inflammatory response at the site of neointimal hyperplasia [21]. In the current study, we explored the implementation of [ 11 C]TZ3321 for assessment of S1PR1 expression in inflammatory lesions in an EAE rat model of MS.…”

Design, Synthesis, and In Vitro and In Vivo Evaluation of an 18F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer

“…28–30 Our group previously reported the radiosynthesis of the 11 C-labeled S1P 1 selective ligand 3-((2-fluoro-4-(5-(2′-methyl-2-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)-(methyl)amino)-propanoic acid 5 ([ 11 C]TZ3321, Figure 2) and demonstrated the feasibility of PET imaging S1P 1 as a measure of inflammatory response in both the femoral artery wire-injury mouse model of restenosis 29 and in the experimental autoimmune encephalomyelitis (EAE) rat model of multiple sclerosis (MS). 30 Here, we present the synthesis and screening of fluorine-containing ligands based on reported compounds with either a benzoxazole core 31 or an oxadiazole core.…”

Specificity vs versatility: A fine balance for novel targeted molecular imaging radiotracers

“…In the current issue of the Journal, Jin and colleagues present a preliminary evaluation of the novel sphingosine-1-phosphate receptor 1 (S1P 1 ) ligand 11 C-TZ3321 for molecular PET imaging of vascular injury, specifically targeting neointimal hyperplasia. 8 Expansion of the vascular intima is associated with increased S1P 1 expression by invading smooth muscle cells, providing an enticing imaging target to non-invasively assess vascular remodeling. In a clinical setting, S1P 1 -expressing vascular smooth muscle cells contribute to in-stent restenosis, a situation for which an imaging biomarker may be of significant benefit.…”