¹⁸F-fluoroethylcholine uptake in arterial vessel walls and cardio vascular risk factors

Summary

Aim: Fluorine-labelled choline derivatives were recently suggested as agents for visualizing vulnerable atherosclerotic plaques. We therefore aimed to evaluate the association between¹⁸F-fluoroethylcholine (FEC) uptake in the wall of large arteries, where calcification was also measured, with the presence of cardiovascular risk factors and occurrence of prior cardiovascular events. Patients, methods: Detailed clinical information, including common cardiovascular risk factors, was obtained retrospectively in 60 prostate cancer patients examined with whole-body FEC PETCT. In each patient, we calculated the mean blood pool-corrected SUV, as well as the mean target-to-background ratio (TBR), in addition to the sum of calcified plaques (CP_sum) from six major vessels: ascending and descending aorta, aortic arch, abdominal aorta, and both iliac arteries. Results: As reported previously, the CP_sum correlated significantly with cardiovascular risk factors, in contrast to mean SUV or TBR scores, which did not show any significance with the presence of cardiovascular risk factors. There was no correlation between CP_sum, mean TBR or SUV, nor was there any significant association of CP_sum, mean TBR or SUV with the prior occurrence of cardio- or cerebrovascular events. Conclusion: Contrary to a recent report, we found in our rather large cohort of elderly prostate cancer patients no significant association between FEC uptake in large vessels and atherosclerotic plaque burden, or the presence of cardiovascular risk factors. In line with prior reports on structural changes in vessels, increased calcified atherosclerotic plaque burden was strongly associated with the occurrence of common cardiovascular risk factors.

Zusammenfassung

Ziel: Fluor-markierte Cholinderivate wurden kürzlich als vielversprechende Radiotracer für die Darstellung vulnerabler atherosklerotischer Plaques vorgestellt. In diesem Zusammenhang haben wir die Assoziation zwischen ¹⁸F-Fluorethylcholin( FEC)-Aufnahme in Gefäßwänden großer arterieller Gefäße, deren Kalzifizierungsgrad ebenfalls gemessen wurde, kardiovaskulären Risikofaktoren und kardiovaskulären Ereignisse untersucht. Patienten, Methoden: An einem Kollektiv von 60 Prostatakarzinom-Patienten wurden detaillierte klinische Informationen erhoben (u. a. kardiovaskuläre Risikofaktoren) und Ganzkörper FEC-PET-CTUntersuchungen durchgeführt. Mittlerer Blutpool-korrigierter SUV, mittlere Target-zu-Background-Ratio (TBR) und die Summe kalzifizierter Plaques (CP_sum) in sechs Gefäßregionen (Aorta ascendens und descendens, Aortenbogen, Aorta abdominalis und Arteriae iliacae) wurden bestimmt. Ergebnisse: Wie in früheren Studien korrelierte CP_sum – im Gegensatz zu den mittleren SUV- und TBR-Werten – signifikant mit dem Vorhandensein kardiovaskulärer Risikofaktoren. Es gab weder signifikante Korrelationen zwischen CP_sum, mittlerem TBR oder mittlerem SUV untereinander, noch signifikante Korrelationen zwischen diesen Parametern und dem früheren Auftreten kardiovaskulärer Ereignisse. Schlussfolgerung: Wir haben in einem relativ großen Prostatakarzinom-Patientenkollektiv keinen signifikanten Zusammenhang zwischen vaskulärer FEC-Aufnahme sowie atherosklerotischer Plaque-Last und kardiovaskulären Risikofaktoren gefunden. In Übereinstimmung mit früheren Studien war jedoch das hohe Aufkommen kalzifizierter athero-sklerotischer Plaques stark mit kardiovaskulären Risikofaktoren assoziiert.

Keywords

Atherosclerosis - plaque - PET - fluoroethyl choline

Schlüsselwörter

Atherosklerose - Plaque - PET - Fluorethyl cholin

^* Both authors contributed equally to this work.

• References

• 1 Weintraub HS. Identifying the vulnerable patient with rupture-prone plaque. Am J Cardiol 2008; 101: 3F-10F.
• 2 Rosamond W, Flegal K, Furie K. et al. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008; 117: e25-146.
• 3 Naghavi M, Libby P, Falk E. et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 2003; 108: 1772-1778.
• 4 Izquierdo-Garcia D, Davies JR, Graves MJ. et al. Comparison of methods for magnetic resonance-guided [¹⁸F]fluorodeoxyglucose positron emission tomography in human carotid arteries: reproducibility, partial volume correction, and correlation between methods. Stroke 2009; 40: 86-93.
• 5 Rudd JH, Myers KS, Bansilal S. et al. ¹⁸Fluorodeoxy-glucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol 2007; 50: 892-896.
• 6 Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352: 1685-1695.
• 7 Izquierdo-Garcia D, Davies JR, Graves MJ. et al. Comparison of methods for magnetic resonance-guided [¹⁸F]fluorodeoxyglucose positron emission tomography in human carotid arteries. Reproducibility, partial volume correction, and correlation between methods. Stroke 2009; 40: 86-93.
• 8 Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med 1999; 340: 115-126.
• 9 Schäfers M, Bengel F, Büll U. et al. Position paper nuclear cardiology: update 2008. Nuklearmedizin 2009; 48: 71-78.
• 10 Lindner O, Burchert W, Bengel FM. et al. Myocardial perfusion scintigraphy 2007 in Germany--results of the query and current status. Nuklearmedizin 2009; 48: 131-137.
• 11 Brown TL, Merrill J, Hill P, Bengel FM. Relationship of coronary calcium and myocardial perfusion in individuals with chest pain. Assessed by integrated rubidium-82 PET-CT. Nuklearmedizin 2008; 47: 255-260.
• 12 Ben-Haim S, Israel O. PET/CT for atherosclerotic plaque imaging. Q J Nucl Med Mol Imaging 2006; 50: 53-60.
• 13 Ben-Haim S, Kupzov E, Tamir A. et al. Changing patterns of abnormal vascular wall ¹⁸F-fluorodeoxy-glucose uptake on follow-up PET/CT studies. J Nucl Cardiol 2006; 13: 791-800.
• 14 Bural GG, Torigian DA, Chamroonrat W. et al. FDG-PET is an effective imaging modality to detect and quantify age-related atherosclerosis in large arteries. Eur J Nucl Med Mol Imaging 2008; 35: 562-569.
• 15 Rudd JH, Myers KS, Bansilal S. et al. Atherosclerosis inflammation imaging with ¹⁸F-FDG PET: Carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med 2008; 49: 871-878.
• 16 Rudd JH, Warburton EA, Fryer TD. et al. Imaging atherosclerotic plaque inflammation with [¹⁸F]-fluorodeoxyglucose positron emission tomography. Circulation 2002; 105: 2708-2711.
• 17 Tahara N, Kai H, Yamagishi S. et al. Vascular inflammation evaluated by [¹⁸F]-fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome. J Am Coll Cardiol 2007; 49: 1533-1539.
• 18 Rominger A, Saam T, Wolpers S. et al. ¹⁸F-FDG PET/ CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 2009; 50: 1611-1620.
• 19 Wyss MT, Weber B, Honer M. et al. ¹⁸F-choline in experimental soft tissue infection assessed with autoradiography and high-resolution PET. Eur J Nucl Med Mol Imaging 2004; 31: 312-316.
• 20 Schmid DT, John H, Zweifel R. et al. Fluorocholine PET/CT in patients with prostate cancer: initial experience. Radiology 2005; 235: 623-628.
• 21 Yoshimoto M, Waki A, Obata A. et al. Radiolabeled choline as a proliferation marker: comparison with radiolabeled acetate. Nucl Med Biol 2004; 31: 859-865.
• 22 Boggs KP, Rock CO, Jackowski S. Lysophosphatidylcholine and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine inhibit the CDP-choline pathway of phosphatidylcholine synthesis at the CTP:phosphocholine cytidylyltransferase step. J Biol Chem 1995; 270: 7757-7764.
• 23 Haeffner EW. Studies on choline permeation through the plasma membrane and its incorporation into phosphatidyl choline of Ehrlich-Lettreascites tumor cells in vitro. Eur J Biochem 1975; 51: 219-228.
• 24 Katz-Brull R, Degani H. Kinetics of choline transport and phosphorylation in human breast cancer cells; NMR application of the zero trans method. Anticancer Res 1996; 16: 1375-1380.
• 25 Ramirez de Molina A, Gutierrez R, Ramos MA. et al. Increased choline kinase activity in human breast carcinomas: clinical evidence for a potential novel antitumor strategy. Oncogene 2002; 21: 4317-4322.
• 26 Kato K, Schober O, Ikeda M. et al. Evaluation and comparison of nC-choline uptake and calcification in aortic and common carotid arterial walls with combined PET/CT. Eur J Nucl Med Mol Imaging 2009; 36: 1622-1628.
• 27 Bucerius J, Schmaljohann J, Bohm I. et al. Feasibility of ¹⁸F-fluoromethylcholine PET/CT for imaging of vessel wall alterations in humans--first results. Eur J Nucl Med Mol Imaging 2008; 35: 815-820.
• 28 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1: 307-310.
• 29 Eisen A, Tenenbaum A, Koren-Morag N. et al. Calcification of the thoracic aorta as detected by spiral computed tomography among stable angina pectoris patients: association with cardiovascular events and death. Circulation 2008; 118: 1328-1334.
• 30 Budoff MJ, Shaw LJ, Liu ST. et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol 2007; 49: 1860-1870.
• 31 Matter CM, Wyss MT, Meier P. et al. ¹⁸F-choline images murine atherosclerotic plaques ex vivo. Arterioscler Thromb Vasc Biol 2006; 26: 584-589.
• 32 Brix G, Lechel U, Glatting G. et al. Radiation exposure of patients undergoing whole-body dual-modality ¹⁸F-FDG PET/CT examinations. J Nucl Med 2005; 46: 608-613.