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DRAFT: Quantification of oxidative metabolism and perfusion with[1-¹¹C]acetate

Theory

After injection of [1-¹¹C]acetate, the washout of radiolabel represents the formation of [¹¹C]CO₂, 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., 2008). 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., 2008); 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 k_mono 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). This model is a simplification of previous five-compartment model (van den Hoff et al., 1996).

Kidney

Juillard et al (2007) showed that k_mono 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 k_mono images.

Cancer imaging

Prostate cancer

Schiepers et al. (2008) observed that MTGA for irreversible uptake (Patlak plot) and 2-tissue compartment model, withk₄ 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

Not recommended as yet.

Heart

For studying myocardial oxygen consumption, the one-exponential fitting (K_mono) 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) will be included in upcoming version of Carimas™.

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.

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.

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 (k_mono) of [¹¹C]acetate using parametric k_mono 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.

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.

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. 2008 (in press).