Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 7/2020

16.11.2019 | Original Article

18F-sodium fluoride PET/CT provides prognostic clarity compared to calcium and Framingham risk scoring when addressing whole-heart arterial calcification

verfasst von: Olivia Sorci, Alexandra S. Batzdorf, Michael Mayer, Sylvia Rhodes, Matthew Peng, Amanda R. Jankelovits, Julia N. Hornyak, Oke Gerke, Poul Flemming Høilund-Carlsen, Abass Alavi, Chamith S. Rajapakse

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 7/2020

Einloggen, um Zugang zu erhalten

Abstract

Aims

To investigate the benefit of utilizing 18F-sodium fluoride (NaF) PET/CT over calcium and Framingham scoring for potential preventative coronary artery disease (CAD) intervention.

Methods and results

This retrospective study included 136 participants (ages 21–75, BMI 18–43 kg/m2): 86 healthy controls and 50 patients. CT heart segmentations were superimposed onto PET images and standard uptake values (SUV) were calculated by a semi-auto segmentation method of drawing volumes of interest around the heart. Intergroup comparisons were made matching 37 patient/control pairs based on age, gender, and BMI. ROC curves were generated to determine how well SUV and Framingham methods predicted patient status. Regressions including all 136 participants were performed between SUV, age, and BMI. Patients exhibited higher average SUV (SUVmean; P = 0.006) and Framingham scores (P = 0.02) than controls. However, ROC curves indicated that SUVmean could discriminate patients from controls (AUC = 0.63, P = 0.049), but Framingham scores could not (AUC = 0.44, P = 0.38). Calcium scores and maximum SUV (SUVmax) did not differ between patients and controls. SUVmean correlated with age and BMI among females (age, partial R2 = 0.16, P = 0.001; BMI, partial R2 = 0.12, P = 0.004) and males (age, partial R2 = 0.28, P < 0.0001; BMI, partial R2 = 0.22, P < 0.0001).

Conclusion

Unlike calcium scores, NaF PET/CT-derived values differed between patients and controls. Framingham risk score patterns echoed those of SUVmean, but were not sensitive enough to predict patient status. SUVmean values increased with age and BMI. Therefore, incorporation of NaF PET/CT into routine prognostic CAD assessment might prove beneficial for assessing early stage plaque calcification in coronary arteries.

Trial registration

ClinicalTrials.​gov (NCT01724749).
Literatur
1.
Zurück zum Zitat Irkle A, Vesey AT, Lewis DY, Skepper JN, JLE B, Dweck MR, et al. Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography. Nature Communications. 2015;6(1). Irkle A, Vesey AT, Lewis DY, Skepper JN, JLE B, Dweck MR, et al. Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography. Nature Communications. 2015;6(1).
2.
Zurück zum Zitat Fleg JL, Stone GW, Fayad ZA, Hatsukami GJF, TS KF, Ohayon J, et al. Detection of high-risk atherosclerotic plaque: report of the NHLBI Working Group on current status and future directions. JACC Cardiovasc Imaging. 2012;5(9):941–55.CrossRef Fleg JL, Stone GW, Fayad ZA, Hatsukami GJF, TS KF, Ohayon J, et al. Detection of high-risk atherosclerotic plaque: report of the NHLBI Working Group on current status and future directions. JACC Cardiovasc Imaging. 2012;5(9):941–55.CrossRef
3.
Zurück zum Zitat Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011;123(4):18–209.CrossRef Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011;123(4):18–209.CrossRef
4.
Zurück zum Zitat Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al. Executive summary: heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010;121(7):948–54.CrossRef Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al. Executive summary: heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010;121(7):948–54.CrossRef
5.
Zurück zum Zitat Siontis GC, Mavridis D, Greenwood JP, Coles B, Nikolakopoulou A, Jüni P, et al. Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials. BMJ. 2018. Siontis GC, Mavridis D, Greenwood JP, Coles B, Nikolakopoulou A, Jüni P, et al. Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials. BMJ. 2018.
6.
Zurück zum Zitat Malguria N, Zimmerman S, Fishman EK. Coronary artery calcium scoring. Journal of Computer Assisted Tomography. 2018;42(6):887–97.CrossRef Malguria N, Zimmerman S, Fishman EK. Coronary artery calcium scoring. Journal of Computer Assisted Tomography. 2018;42(6):887–97.CrossRef
7.
Zurück zum Zitat Willemink MJ, Werf NRVD, Nieman K, Greuter MJ, Koweek LM, Fleischmann D. Coronary artery calcium: a technical argument for a new scoring method. Journal of Cardiovascular Computed Tomography. 2018. Willemink MJ, Werf NRVD, Nieman K, Greuter MJ, Koweek LM, Fleischmann D. Coronary artery calcium: a technical argument for a new scoring method. Journal of Cardiovascular Computed Tomography. 2018.
8.
Zurück zum Zitat Rumberger JA, Kaufman L. A rosetta stone for coronary calcium risk stratification: Agatston, volume, and mass scores in 11,490 individuals. AJR Am J Roentgenol. 2003;181(3):743–8.CrossRef Rumberger JA, Kaufman L. A rosetta stone for coronary calcium risk stratification: Agatston, volume, and mass scores in 11,490 individuals. AJR Am J Roentgenol. 2003;181(3):743–8.CrossRef
9.
Zurück zum Zitat Ulzheimer S, Kalender WA. Assessment of calcium scoring performance in cardiac computed tomography. Eur Radiol. 2003;13(3):484–97.CrossRef Ulzheimer S, Kalender WA. Assessment of calcium scoring performance in cardiac computed tomography. Eur Radiol. 2003;13(3):484–97.CrossRef
10.
Zurück zum Zitat Blomberg BA, Thomassen A, Takx RAP, Vilstrup MH, Hess S, Nielsen AL, et al. Delayed sodium 18F-fluoride PET/CT imaging does not improve quantification of vascular calcification metabolism: Results from the CAMONA study. Journal of Nuclear Cardiology. 2013;21(2):293–304.CrossRef Blomberg BA, Thomassen A, Takx RAP, Vilstrup MH, Hess S, Nielsen AL, et al. Delayed sodium 18F-fluoride PET/CT imaging does not improve quantification of vascular calcification metabolism: Results from the CAMONA study. Journal of Nuclear Cardiology. 2013;21(2):293–304.CrossRef
11.
Zurück zum Zitat Blomberg BA, Thomassen A, Jong PAD, Lam MG, Diederichsen AC, Olsen MH, et al. Coronary fluorine-18-sodium fluoride uptake is increased in healthy adults with an unfavorable cardiovascular risk profile. Nuclear Medicine Communications. 2017;38(11):1007–14.CrossRef Blomberg BA, Thomassen A, Jong PAD, Lam MG, Diederichsen AC, Olsen MH, et al. Coronary fluorine-18-sodium fluoride uptake is increased in healthy adults with an unfavorable cardiovascular risk profile. Nuclear Medicine Communications. 2017;38(11):1007–14.CrossRef
12.
Zurück zum Zitat Blomberg BA, Jong PAD, Thomassen A, Lam MGE, Vach W, Olsen MH, et al. Thoracic aorta calcification but not inflammation is associated with increased cardiovascular disease risk: results of the CAMONA study. European Journal of Nuclear Medicine and Molecular Imaging. 2016;44(2):249–58.CrossRef Blomberg BA, Jong PAD, Thomassen A, Lam MGE, Vach W, Olsen MH, et al. Thoracic aorta calcification but not inflammation is associated with increased cardiovascular disease risk: results of the CAMONA study. European Journal of Nuclear Medicine and Molecular Imaging. 2016;44(2):249–58.CrossRef
13.
Zurück zum Zitat Dweck MR, Chow MW, Joshi NV, Williams MC, Jones C, Fletcher AM, et al. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol. 2012;59(17):1539–48.CrossRef Dweck MR, Chow MW, Joshi NV, Williams MC, Jones C, Fletcher AM, et al. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol. 2012;59(17):1539–48.CrossRef
14.
Zurück zum Zitat Joshi NV, Vesey AT, Williams MC, Shah AS, Calvert PA, Craighead FH, et al. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet. 2014;383(9918):705–13.CrossRef Joshi NV, Vesey AT, Williams MC, Shah AS, Calvert PA, Craighead FH, et al. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet. 2014;383(9918):705–13.CrossRef
15.
Zurück zum Zitat Moss AJ, Doris MK, Andrews JPM, Bing R, Daghem M, van Beek EJR, et al. Molecular coronary plaque imaging using (18)F-fluoride. Circ Cardiovasc Imaging. 2019;12(8):e008574.CrossRef Moss AJ, Doris MK, Andrews JPM, Bing R, Daghem M, van Beek EJR, et al. Molecular coronary plaque imaging using (18)F-fluoride. Circ Cardiovasc Imaging. 2019;12(8):e008574.CrossRef
16.
Zurück zum Zitat Li L, Li X, Jia Y, Fan J, Wang H, Fan C, et al. Sodium-fluoride PET-CT for the non-invasive evaluation of coronary plaques in symptomatic patients with coronary artery disease: a cross-correlation study with intravascular ultrasound. Eur J Nucl Med Mol Imaging. 2018;45(12):2181–9.CrossRef Li L, Li X, Jia Y, Fan J, Wang H, Fan C, et al. Sodium-fluoride PET-CT for the non-invasive evaluation of coronary plaques in symptomatic patients with coronary artery disease: a cross-correlation study with intravascular ultrasound. Eur J Nucl Med Mol Imaging. 2018;45(12):2181–9.CrossRef
17.
Zurück zum Zitat Blomberg BA, Thomassen A, Jong PAD, Simonsen JA, Lam MGEH, Nielsen AL, et al. Impact of personal characteristics and technical factors on quantification of sodium 18F-fluoride uptake in human arteries: prospective evaluation of healthy subjects. Journal of Nuclear Medicine. 2015;56(10):1534–40.CrossRef Blomberg BA, Thomassen A, Jong PAD, Simonsen JA, Lam MGEH, Nielsen AL, et al. Impact of personal characteristics and technical factors on quantification of sodium 18F-fluoride uptake in human arteries: prospective evaluation of healthy subjects. Journal of Nuclear Medicine. 2015;56(10):1534–40.CrossRef
18.
Zurück zum Zitat Tarkin JM, Dweck MR, Evans NR, Takx RAP, Brown AJ, Tawakol A, et al. Imaging atherosclerosis. Circulation Research. 2016;118:750–69.CrossRef Tarkin JM, Dweck MR, Evans NR, Takx RAP, Brown AJ, Tawakol A, et al. Imaging atherosclerosis. Circulation Research. 2016;118:750–69.CrossRef
19.
Zurück zum Zitat Mortality GBD. Causes of Death C. Global, regional, and national age-sex specific all cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385(9963):117–71.CrossRef Mortality GBD. Causes of Death C. Global, regional, and national age-sex specific all cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385(9963):117–71.CrossRef
20.
Zurück zum Zitat Tarkin JM, Dweck MR, Evans NR, Takx RAP, Brown AJ, Tawakol A, et al. Imaging atherosclerosis. Circulation Research. 2016;118:750–69.CrossRef Tarkin JM, Dweck MR, Evans NR, Takx RAP, Brown AJ, Tawakol A, et al. Imaging atherosclerosis. Circulation Research. 2016;118:750–69.CrossRef
21.
Zurück zum Zitat Beheshti M, Saboury B, Mehta NN, Torigian DA, Werner T, Mohler E, et al. Detection and global quantification of cardiovascular molecular calcification by fluoro18-fluoride positron emission tomography/computed tomography--a novel concept. Hell J Nucl Med. 2011;14:114–21.20.PubMed Beheshti M, Saboury B, Mehta NN, Torigian DA, Werner T, Mohler E, et al. Detection and global quantification of cardiovascular molecular calcification by fluoro18-fluoride positron emission tomography/computed tomography--a novel concept. Hell J Nucl Med. 2011;14:114–21.20.PubMed
22.
Zurück zum Zitat Yoon W, Crisostomo P, Halandras P, Bechara C, Aulivola B. The utility of the Agatston calcium score in predicting carotid plaque vulnerability. Annals of Vascular Surgery. 2018;48:6–7.CrossRef Yoon W, Crisostomo P, Halandras P, Bechara C, Aulivola B. The utility of the Agatston calcium score in predicting carotid plaque vulnerability. Annals of Vascular Surgery. 2018;48:6–7.CrossRef
23.
Zurück zum Zitat Al-Mallah MH. Coronary artery calcium scoring: do we need more prognostic data prior to adoption in clinical practice. JACC: Cardiovascular Imaging. 2018;11(12):1807–9.PubMed Al-Mallah MH. Coronary artery calcium scoring: do we need more prognostic data prior to adoption in clinical practice. JACC: Cardiovascular Imaging. 2018;11(12):1807–9.PubMed
24.
Zurück zum Zitat Allam AHA, Thompson RC, Eskander MA, Ali MAM, Sadek A, Rowan CJ, et al. Is coronary calcium scoring too late? Total body arterial calcium burden in patients without known CAD and normal MPI. Journal of Nuclear Cardiology. 2017;25(6):1990–8.CrossRef Allam AHA, Thompson RC, Eskander MA, Ali MAM, Sadek A, Rowan CJ, et al. Is coronary calcium scoring too late? Total body arterial calcium burden in patients without known CAD and normal MPI. Journal of Nuclear Cardiology. 2017;25(6):1990–8.CrossRef
25.
Zurück zum Zitat Derlin T, Wisotzki C, Richter U, Apostolova I, Bannas P, Weber C, et al. In vivo imaging of mineral deposition in carotid plaque using 18F-sodium fluoride PET/CT: correlation with atherogenic risk factors. Journal of Nuclear Medicine. 2011;52(3):362–8.CrossRef Derlin T, Wisotzki C, Richter U, Apostolova I, Bannas P, Weber C, et al. In vivo imaging of mineral deposition in carotid plaque using 18F-sodium fluoride PET/CT: correlation with atherogenic risk factors. Journal of Nuclear Medicine. 2011;52(3):362–8.CrossRef
26.
Zurück zum Zitat Morbelli S, Fiz F, Piccardo A, Picori L, Massollo M, Pestarino E, et al. Divergent determinants of 18F–NaF uptake and visible calcium deposition in large arteries: relationship with Framingham risk score. The International Journal of Cardiovascular Imaging. 2013;30(2):439–47.CrossRef Morbelli S, Fiz F, Piccardo A, Picori L, Massollo M, Pestarino E, et al. Divergent determinants of 18F–NaF uptake and visible calcium deposition in large arteries: relationship with Framingham risk score. The International Journal of Cardiovascular Imaging. 2013;30(2):439–47.CrossRef
27.
Zurück zum Zitat Raynor W, Houshmand S, Gholami S, Emamzadehfard S, Rajapakse CS, Blomberg AB, et al. Evolving role of molecular imaging with 18F-sodium fluoride PET/CT as a biomarker for calcium metabolism. Osteoporosis Reports. 2016;4:115–25.CrossRef Raynor W, Houshmand S, Gholami S, Emamzadehfard S, Rajapakse CS, Blomberg AB, et al. Evolving role of molecular imaging with 18F-sodium fluoride PET/CT as a biomarker for calcium metabolism. Osteoporosis Reports. 2016;4:115–25.CrossRef
28.
Zurück zum Zitat Czernin J, Satyamurthy N, Schiepers C. Molecular mechanisms of bone 18F-NaF deposition. Journal of Nuclear Medicine. 2010;51:1826–9.CrossRef Czernin J, Satyamurthy N, Schiepers C. Molecular mechanisms of bone 18F-NaF deposition. Journal of Nuclear Medicine. 2010;51:1826–9.CrossRef
31.
Zurück zum Zitat van der Valk FM, Kroon J, Potters WV, Thurlings RM, Bennink RJ, Verberne HJ, Nederveen AJ, Nieuwdorp M, Mulder WJ, Fayad ZA, van Buul JD, Stroes ES. In vivo imaging of enhanced leukocyte accumulation in atherosclerotic lesions in humans. J Am Coll Cardiol. 2014;64:1019– 1029. https://doi.org/10.1016/j.jacc.2014.06.11. van der Valk FM, Kroon J, Potters WV, Thurlings RM, Bennink RJ, Verberne HJ, Nederveen AJ, Nieuwdorp M, Mulder WJ, Fayad ZA, van Buul JD, Stroes ES. In vivo imaging of enhanced leukocyte accumulation in atherosclerotic lesions in humans. J Am Coll Cardiol. 2014;64:1019– 1029. https://​doi.​org/​10.​1016/​j.​jacc.​2014.​06.​11.​
32.
Zurück zum Zitat Derlin T, Richter U, Bannas P, Begemann P, Buchert R, Mester J, et al. Feasibility of 18F-sodium fluoride PET/CT for imaging of atherosclerotic plaque. Journal of Nuclear Medicine. 2010;51(6):862–5.CrossRef Derlin T, Richter U, Bannas P, Begemann P, Buchert R, Mester J, et al. Feasibility of 18F-sodium fluoride PET/CT for imaging of atherosclerotic plaque. Journal of Nuclear Medicine. 2010;51(6):862–5.CrossRef
33.
Zurück zum Zitat Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation. 2005;111(25):3481–8.CrossRef Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation. 2005;111(25):3481–8.CrossRef
34.
Zurück zum Zitat Tiong AY, Brieger D. Inflammation and coronary artery disease. Am Heart J. 2005;150(1):11–8.CrossRef Tiong AY, Brieger D. Inflammation and coronary artery disease. Am Heart J. 2005;150(1):11–8.CrossRef
35.
Zurück zum Zitat Hanson MA, Fareed MT, Argenio SL, Agunwamba AO, Hanson TR. Coronary artery disease. Prim Care. 2013;40(1):1–16.CrossRef Hanson MA, Fareed MT, Argenio SL, Agunwamba AO, Hanson TR. Coronary artery disease. Prim Care. 2013;40(1):1–16.CrossRef
36.
Zurück zum Zitat Janssen T, Bannas P, Herrmann J, Veldhoen S, Busch JD, Treszl A, et al. Association of linear 18F-sodium fluoride accumulation in femoral arteries as a measure of diffuse calcification with cardiovascular risk factors: a PET/CT study. Journal of Nuclear Cardiology. 2013;20(4):569–77.CrossRef Janssen T, Bannas P, Herrmann J, Veldhoen S, Busch JD, Treszl A, et al. Association of linear 18F-sodium fluoride accumulation in femoral arteries as a measure of diffuse calcification with cardiovascular risk factors: a PET/CT study. Journal of Nuclear Cardiology. 2013;20(4):569–77.CrossRef
37.
Zurück zum Zitat Barquera S, Pedroza-Tobías A, Medina C, Hernández-Barrera L, Bibbins-Domingo K, Lozano R, et al. Global overview of the epidemiology of atherosclerotic cardiovascular disease. Archives of Medical Research. 2015;46(5):328–38.CrossRef Barquera S, Pedroza-Tobías A, Medina C, Hernández-Barrera L, Bibbins-Domingo K, Lozano R, et al. Global overview of the epidemiology of atherosclerotic cardiovascular disease. Archives of Medical Research. 2015;46(5):328–38.CrossRef
38.
Zurück zum Zitat Wilson P. Established risk factor and coronary artery disease: The Framingham Study. American Journal of Hypertension. 1997;7(7):7–12. Wilson P. Established risk factor and coronary artery disease: The Framingham Study. American Journal of Hypertension. 1997;7(7):7–12.
Metadaten
Titel
18F-sodium fluoride PET/CT provides prognostic clarity compared to calcium and Framingham risk scoring when addressing whole-heart arterial calcification
verfasst von
Olivia Sorci
Alexandra S. Batzdorf
Michael Mayer
Sylvia Rhodes
Matthew Peng
Amanda R. Jankelovits
Julia N. Hornyak
Oke Gerke
Poul Flemming Høilund-Carlsen
Abass Alavi
Chamith S. Rajapakse
Publikationsdatum
16.11.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 7/2020
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-019-04590-3

Weitere Artikel der Ausgabe 7/2020

European Journal of Nuclear Medicine and Molecular Imaging 7/2020 Zur Ausgabe