Top

Published in:

01-04-2017 | Original Article

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

Authors: Hongjun Jin, PhD, Hao Yang, PhD, Hui Liu, MD, PhD, Yunxiao Zhang, PhD, Xiang Zhang, PhD, Adam J. Rosenberg, PhD, Yongjian Liu, PhD, Suzanne E. Lapi, PhD, Zhude Tu, PhD

Published in: Journal of Nuclear Cardiology | Issue 2/2017

Abstract

Background

Sphingosine-1-phosphate receptor 1 (S1PR1) is highly expressed in vascular smooth muscle cells from intimal lesions. PET imaging using S1PR1 as a biomarker would increase our understanding of its role in vascular pathologies including in-stent restenosis.

Methods

The S1PR1 compound TZ3321 was synthesized for in vitro characterization and labeled with Carbon-11 for in vivo studies. The biodistribution of [¹¹C]TZ3321 was evaluated in normal mice; microPET and immunohistochemistry (IHC) studies were performed using a murine femoral artery wire-injury model of restenosis.

Results

The high potency of TZ3321 for S1PR1 (IC ₅₀ = 2.13 ± 1.63 nM), and high selectivity (>1000 nM) for S1PR1 over S1PR2 and S1PR3 were confirmed. Biodistribution data revealed prolonged retention of [¹¹C]TZ3321 in S1PR1-enriched tissues. MicroPET imaging of [¹¹C]TZ3321 showed higher uptake in the wire-injured arteries of ApoE^−/− mice than in injured arteries of wild-type mice (SUV 0.40 ± 0.06 vs 0.28 ± 0.04, n = 6, P < .001); FDG-PET showed no difference (SUV 0.98 ± 0.04 vs 0.94 ± 0.01, n = 6, P > .05). Post-PET autoradiography showed >4-fold higher [¹¹C]TZ3321 retention in the injured artery of ApoE^−/− mice than in wild-type mice. Subsequent IHC staining confirmed higher expression of S1PR1 in the neointima of the injured artery of ApoE^−/− mice than in wild-type mice.

Conclusions

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

Available only for authorised users

Slavin L, Chhabra A, Tobis JM. Drug-eluting stents: Preventing restenosis. Cardiol Rev 2007;15:1-12.CrossRefPubMed

Ishii H, Kataoka T, Kobayashi Y, Tsumori T, Takeshita H, Matsumoto R, et al. Utility of myocardial fractional flow reserve for prediction of restenosis following sirolimus-eluting stent implantation. Heart Vessels 2011;26:572-81.CrossRefPubMed

Joshi F, Rosenbaum D, Bordes S, Rudd JH. Vascular imaging with positron emission tomography. J Intern Med 2011;270:99-109.CrossRefPubMed

Lowe HC, Oesterle SN, Khachigian LM. Coronary in-stent restenosis: Current status and future strategies. J Am Coll Cardiol 2002;39:183-93.CrossRefPubMed

Virmani R, Farb A. Pathology of in-stent restenosis. Curr Opin Lipidol 1999;10:499-506.CrossRefPubMed

Mehta NN, Torigian DA, Gelfand JM, Saboury B, Alavi A. Quantification of atherosclerotic plaque activity and vascular inflammation using [¹⁸F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). J Vis Exp 2012;2012:e3777.

Trad S, Bensimhon L, El Hajjam M, Chinet T, Wechsler B, Saadoun D. ¹⁸F-Fluorodeoxyglucose-positron emission tomography scanning is a useful tool for therapy evaluation of arterial aneurysm in Behçet’s disease. Joint Bone Spine 2013;80:420-3.CrossRefPubMed

Spiegel S, Milstien S. Sphingosine 1-phosphate, a key cell signaling molecule. J Biol Chem 2002;277:25851-4.CrossRefPubMed

Kluk MJ, Hla T. Role of the sphingosine 1-phosphate receptor EDG-1 in vascular smooth muscle cell proliferation and migration. Circ Res 2001;89:496-502.CrossRefPubMed

10.

Wamhoff BR, Lynch KR, Macdonald TL, Owens GK. Sphingosine-1-phosphate receptor subtypes differentially regulate smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol 2008;28:1454-61.CrossRefPubMedPubMedCentral

11.

Sim-Selley LJ, Goforth PB, Mba MU, Macdonald TL, Lynch KR, Milstien S, et al. Sphingosine-1-phosphate receptors mediate neuromodulatory functions in the CNS. J Neurochem 2009;110:1191-202.CrossRefPubMedPubMedCentral

12.

Obinata H, Hla T. Fine-tuning S1P therapeutics. Chem Biol 2012;19:1080-2.CrossRefPubMedPubMedCentral

13.

Fujii Y, Ueda Y, Ohtake H, Ono N, Takayama T, Nakazawa K, et al. Blocking S1P interaction with S1P₁ receptor by a novel competitive S1P₁-selective antagonist inhibits angiogenesis. Biochem Biophys Res Commun 2012;419:754-60.CrossRefPubMed

14.

Quattropani A, Montagne C, Sauer W, Crosignani S, Bombrun A. Oxadiazole Derivatives WO 2010112461 A1. In: Organizations WP editor; 2010.

15.

Reis ED, Roque M, Dansky H, Fallon JT, Badimon JJ, Cordon-Cardo C, et al. Sulindac inhibits neointimal formation after arterial injury in wild-type and apolipoprotein E-deficient mice. Proc Natl Acad Sci USA 2000;97:12764-9.CrossRefPubMedPubMedCentral

16.

Roque M, Fallon JT, Badimon JJ, Zhang WX, Taubman MB, Reis ED. Mouse model of femoral artery denudation injury associated with the rapid accumulation of adhesion molecules on the luminal surface and recruitment of neutrophils. Arterioscler Thromb Vasc Biol 2000;20:335-42.CrossRefPubMed

17.

Boccuzzi SJ, Weintraub WS, Kosinski AS, Roehm JB, Klein JL. Aggressive lipid lowering in postcoronary angioplasty patients with elevated cholesterol (the Lovastatin Restenosis Trial). Am J Cardiol 1998;81:632-6.CrossRefPubMed

18.

Kesavalu L, Lucas AR, Verma RK, Liu L, Dai E, Sampson E, et al. Increased atherogenesis during Streptococcus mutans infection in ApoE-null mice. J Dent Res 2012;91:255-60.CrossRefPubMedPubMedCentral

19.

Leidenfrost JE, Khan MF, Boc KP, Villa BR, Collins ET, Parks WC, et al. A model of primary atherosclerosis and post-angioplasty restenosis in mice. Am J Pathol 2003;163:773-8.CrossRefPubMedPubMedCentral

20.

Rosenberg AJ, Liu H, Tu Z. A practical process for the preparation of [³²P]S1P and binding assay for S1P receptor ligands. Appl Radiat Isot 2015;102:5-9.CrossRefPubMedPubMedCentral

21.

Maceyka M, Milstien S, Spiegel S. Measurement of mammalian sphingosine-1-phosphate phosphohydrolase activity in vitro and in vivo. Methods Enzymol 2007;434:243-56.CrossRefPubMed

22.

Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J, et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 2002;296:346-9.CrossRefPubMed

23.

Schurer SC, Brown SJ, Gonzalez-Cabrera PJ, Schaeffer MT, Chapman J, Jo E, et al. Ligand-binding pocket shape differences between sphingosine 1-phosphate (S1P) receptors S1P1 and S1P3 determine efficiency of chemical probe identification by ultrahigh-throughput screening. ACS Chem Biol 2008;3:486-98.CrossRefPubMedPubMedCentral

24.

Prasad VP, Wagner S, Keul P, Hermann S, Levkau B, Schafers M, et al. Synthesis of fluorinated analogues of sphingosine-1-phosphate antagonists as potential radiotracers for molecular imaging using positron emission tomography. Bioorganic Med Chem 2014;22:5168-81.CrossRef

25.

Sadeghi MM. The pathobiology of the vessel wall: Implications for imaging. J Nucl Cardiol 2006;13:402-14.CrossRefPubMed

26.

Shimizu T, De Wispelaere A, Winkler M, D’Souza T, Caylor J, Chen L, et al. Sphingosine-1-phosphate receptor 3 promotes neointimal hyperplasia in mouse iliac-femoral arteries. Arterioscler Thromb Vasc Biol 2012;32:955-61.CrossRefPubMedPubMedCentral

27.

Tanaskovic S, Isenovic ER, Radak D. Inflammation as a marker for the prediction of internal carotid artery restenosis following eversion endarterectomy: Evidence from clinical studies. Angiology 2011;62:535-42.CrossRefPubMed

28.

Zhao C, Yang L, Mao L, Zhong L, Li X, Wei S. Cystatin C associates with the prediction of in-stent restenosis among patients receiving stent implantation: Results of the 1-year follow-up. Coron Artery Dis 2013;24:357-60.CrossRefPubMed

29.

Rokka J, Federico C, Jurttila J, Snellman A, Haaparanta M, Rinne JO, et al. ¹⁹F/¹⁸F Exchange synthesis for a novel [¹⁸F]S1P3-radiopharmaceutical. J Label Compd Radiopharm 2013;56:385-91.CrossRef

30.

Qu W, Ploessl K, Truong H, Kung MP, Kung HF. Iodophenyl tagged sphingosine derivatives: Synthesis and preliminary biological evaluation. Bioorg Med Chem Lett 2009;19:3382-5.CrossRefPubMed

31.

Briard E, Orain D, Beerli C, Billich A, Streiff M, Bigaud M, et al. BZM055, an iodinated radiotracer candidate for PET and SPECT imaging of myelin and FTY720 brain distribution. ChemMedChem 2011;6:667-77.CrossRefPubMed

32.

Gorenberg M, Bar-Shalom R, Israel O. Patterns of FDG uptake in post-thoracotomy surgical scars in patients with lung cancer. Br J Radiol 2008;81:821-5.CrossRefPubMed

33.

Amano T, Matsubara T, Izawa H, Torigoe M, Yoshida T, Hamaguchi Y, et al. Impact of plasma aldosterone levels for prediction of in-stent restenosis. Am J Cardiol 2006;97:785-8.CrossRefPubMed

34.

Funada R, Oikawa Y, Yajima J, Matsuno S, Kano H, Kirigaya H, et al. Prediction of late restenosis after sirolimus-eluting stent implantation using serial quantitative angiographic and intravascular ultrasound analysis. Cardiovasc Interv Ther 2011;26:26-32.CrossRefPubMed

35.

Weingartner O, Kasper M, Reynen K, Bramke S, Marquetant R, Sedding DG, et al. Comparative morphometric and immunohistological assessment of the development of restenosis after arterial injury and a cholesterol-rich diet in apolipoprotein E^−/− mice and C57BL/6 control mice. Coron Artery Dis 2005;16:391-400.CrossRefPubMed

Title: A promising carbon-11-labeled sphingosine-1-phosphate receptor 1-specific PET tracer for imaging vascular injury
Authors: Hongjun Jin, PhD
Hao Yang, PhD
Hui Liu, MD, PhD
Yunxiao Zhang, PhD
Xiang Zhang, PhD
Adam J. Rosenberg, PhD
Yongjian Liu, PhD
Suzanne E. Lapi, PhD
Zhude Tu, PhD
Publication date: 01-04-2017
Publisher: Springer US
Published in: Journal of Nuclear Cardiology / Issue 2/2017
Print ISSN: 1071-3581
Electronic ISSN: 1532-6551
DOI: https://doi.org/10.1007/s12350-015-0391-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2017

CME instructions: Conducting and interpreting high-quality systematic reviews and meta-analyses

Perfusion imaging using rubidium-82 (82Rb) PET in rats with myocardial infarction: First small animal cardiac 82Rb-PET

Arrhythmias in vasodilator stress testing

Functional versus anatomical approach in stable coronary artery disease patients: Perspective of low- and middle-income countries

Quantitative relationship between coronary artery calcium and myocardial blood flow by hybrid rubidium-82 PET/CT imaging in patients with suspected coronary artery disease

Accuracy of myocardial perfusion imaging in detecting multivessel coronary artery disease: A cardiac CZT study