Quantification of oxidative metabolism and perfusion with [1-11C]Acetate
Theory
After injection of [1-11C]acetate, the build-up phase of radioactivity in the tissue is related (but not linearly) to tissue perfusion, and washout of radiolabel represents the formation of [11C]CO2 in tissue, and is therefore related to oxygen consumption (Buck et al., 1991; Klein et al., 2001).
Published analysis methods
Brain
Total cerebral oxygen consumption can be measured using inhaled [15O]O2, but brain activation induced changes of astrocytic oxidative metabolism can be measured using [1-11C]acetate (Wyss et al., 2009). Wyss et al. (2008) used traditional one-tissue compartment model fitting to estimate K1 and k2, with blood volume fraction fixed to 0.05. Metabolite corrected arterial plasma TAC was used as model input: measured blood curves were converted to plasma curves using quadratic polynomial function, which was fitted to plasma/blood-ratios from rat studies (Wyss et al., 2009); metabolite correction was based on previously published metabolite fractions in humans (Buck et al., 1991). K1 was weakly correlated with perfusion (because of low extraction), but k2 seemed to be more correlated with oxygen metabolism than perfusion.
Heart
Clearance of [11C]-acetate from the myocardium has been found to be bi-exponential (Brown et al., 1988 and 1989; Armbrecht et al., 1989). Buxton et al. (1989), Armbrecht et al. (1989) and Sun et al. (1998) validated that k1 from bi-exponential and kmono from mono-exponential clearance estimation were correlated with measured myocardial oxygen consumption. Several compartmental models have been presented to estimate myocardial oxygen consumption, as reviewed by Klein et al. (2001).
One-tissue compartment model analysis of [1-11C]acetate data allows also quantification of myocardial perfusion at rest as well as under stress conditions (van den Hoff et al., 2001; Sörensen et al., 2010). This model is a simplification of previous five-compartment model (van den Hoff et al., 1996), and performed best in comparison to three other models (Timmer et al., 2010). It was found to provide MBF values in fairly good agreement with actual perfusion values in both healthy individuals and patients with hypertrophic cardiomyopathy over physiological flow ranges under baseline conditions (Timmer et al., 2010). Arterial blood curve is extracted from left ventricular region, and corrected for metabolism using population-based function.
Kidney
Juillard et al (2007) showed that kmono can be calculated from a mono-exponential fit and that it correlates well with renal oxidative metabolism. Hussain et al. (2009) validated the calculation of parametric kmono images.
Cancer imaging
Prostate cancer
Schiepers et al. (2008) observed that MTGA for irreversible uptake (Patlak plot) and 2-tissue compartment model, with k4 set to zero, can be used to study the metabolic activity of prostate tumors. Blood metabolites were corrected using previously estimated metabolite function. SUV will be sufficient in clinical practice (Schiepers et al., 2008).
Suggested analysis methods in Turku PET Centre
Brain
No recommendation as yet.
Heart
For studying myocardial oxygen consumption, the one-exponential fitting (Kmono) is recommended for its simplicity. This method is included in Carimas™.
One-tissue compartmental model for the estimation of myocardial perfusion (van den Hoff et al., 2001; TPCMOD0039) is included in Carimas™ 2.0.
Carimas™ user documentation contains further assistance on using the software.
References:
Armbrecht JJ, Buxton DB, Brunken RC, Phelps ME, Schelbert HR. Regional myocardial oxygen consumption determined noninvasively in humans with [1-11C]acetate and dynamic positron tomography. Circulation 1989; 80: 863–872.
Brown MA, Myears DW, Bergmann SR. Noninvasive assessment of canine myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography. J. Am. Coll. Cardiol. 1988; 12: 1054–1063.
Brown MA, Myears DW, Bergmann SR. Validity of estimates of myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography despite altered patterns of substrate utilization. J. Nucl. Med. 1989; 30: 187–193.
Buxton DB, Nienaber CA, Luxen A, Ratib O, Hansen H, Phelps ME, Schelbert HR. Noninvasive quantitation of regional myocardial oxygen consumption in vivo with [1-11C]acetate and dynamic positron emission tomography. Circulation 1989; 79: 134–142.
Buck A, Wolpers HG, Hutchins GD, Savas V, Mangner TJ, Nguyen N, Schwaiger M. Effect of carbon-11-acetate recirculation on estimates of myocardial oxygen consumption by PET. J. Nucl. Med. 1991; 32: 1950-1957.
Han C, Oikonen V. Model equations for myocardial perfusion studies with [1-11C]acetate PET. TPCMOD0039.
van den Hoff J, Burchert W, Wolpers HG, Meyer GJ, Hundeshagen H. A kinetic model for cardiac PET with [1-carbon-11]-acetate. J. Nucl. Med. 1996; 37: 521-529.
van den Hoff J, Burchert W, Börner A-R, Fricke H, Kühnel G, Meyer GJ, Otto D, Weckesser E, Wolpers H-G, Knapp WH. [1-11C]-acetate as a quantitative perfusion tracer in myocardial PET. J. Nucl. Med. 2001; 42: 1174-1182.
Hussain R, Kudo T, Tsujikawa T, Kobayashi M, Fujibayashi Y, Okazawa H. Validation of the calculation of the clearance rate constant (kmono) of [11C]acetate using parametric kmono image for myocardial oxidative metabolism. Nucl. Med. Biol. 2009; 36: 877-882.
Juillard L, Lemoine S, Janier MF, Barthez PY, Bonnefoi F, Laville M. Validation of renal oxidative metabolism measurement by positron-emission tomography. Hypertension 2007; 50:242-247.
Klein LJ, Visser FC, Knaapen P, Peters JH, Teule GJJ, Visser CA, Lammertsma AA. Carbon-11 acetate as a tracer of myocardial oxygen consumption. Eur. J. Nucl. Med. 2001; 28: 651-668.
Schiepers C, Hoh CK, Nuyts J, Seltzer M, Wu C, Huang S-C, Dahlbom M. 1-11C-acetate kinetics of prostate cancer. J. Nucl. Med. 2008; 49(2): 206-215.
Sun KT, Yeatman A, Buxton DB, Chen K, Johnson JA, Huang S-C, Kofoed KF, Weismueller S, Czernin J, Phelps M, Schelbert HR. Simultaneous measurement of myocardial oxygen consumption and blood flow using [1-carbon-11]acetate. J. Nucl. Med. 1998; 39: 272–280.
Sörensen, J, Valind S, Andersson LG. Simultaneous quantification of myocardial perfusion, oxidative metabolism, cardiac efficiency and pump function at rest and during supine bicycle exercise using 1-11C-acetate PET – a pilot study. Clin. Physiol. Funct. Imaging 2010; 30: 279–284.
Timmer SA, Lubberink M, Germans T, Götte MJ, ten Berg JM, ten Cate FJ, van Rossum AC, Lammertsma AA, Knaapen P. Potential of [11C]acetate for measuring myocardial blood flow: Studies in normal subjects and patients with hypertrophic cardiomyopathy. J Nucl Cardiol. 2010; 17(2): 264-275.
Wyss MT, Weber B, Tryer V, Heer S, Pellerin L, Magistretti PJ, Buck A. Stimulation-induced increases of astrocytic oxidative metabolism in rats and humans investigated with 1-11C-acetate. J. Cereb. Blood Flow Metab. 2009; 29: 44-56.
|
