Background

[PubMed]

Acetate is readily taken up by cells and is activated to acetyl-CoA in both the cytosol and mitochondria by acetyl-CoA synthetase. Acetyl-CoA is a common metabolic intermediate for synthesis of cholesterol and fatty acids, which are then incorporated into membrane (1). Acetyl-CoA is also oxidized in mitrochondria by the tricarboxylic acid (TCA) cycle to carbon dioxide and water. Some of the acetate is converted to amino acids. In normal myocardium, acetate is metabolized to CO₂ via the TCA cycle as the dominant pathway. In contrast, tumor cells convert most of the acetate into fatty acids by a key enzyme fatty acid synthetase (FAS), which is over-expressed in cancer cells (2). Acetate is predominantly incorporated into intracellular phosphatidylcholine membrane microdomains that are important for tumor growth and metastasis (3). [¹¹C]Acetate are used as a positron emission tomography (PET) tracer for studying myocardial oxidative metabolism and regional myocardial blood flow (4). [¹¹C]Acetate is a promising PET tracer for renal, pancreatic, and prostate tumors (5).

Synthesis

[PubMed]

[¹¹C]Acetate is commonly produced by a reaction of methylmagnesium bromide or chloride and [¹¹C]carbon dioxide. This method produces [¹¹C]acetate in a radiochemical yield of 72 ± 12% in 20 min and in high specific activity (>18.5 GBq/µmol, 0.5 Ci/µmol). The radiochemical purity of [¹¹C]acetate was found to be > 95% (6). Several automated systems provided radiochemical yields of 60 - 80% and radiochemical purity of 99% in 15 - 23 min (7-9)

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Acetate uptake and metabolism were studied in four tumor cell lines and one fibroblast cell line with [¹⁴C]acetate. All four tumor cell lines showed higher accumulation of [¹⁴C] activity than the resting fibroblasts. Tumor-to-fibroblast ratios were larger than those of [³H]-2-deoxyglucose. [¹⁴C]Acetate was metabolized and incorporated into phosphatidylcholine and neutral lipids in proportionally to cellular proliferation rates. The remaining fraction of [¹⁴C]acetate was converted to amino acids, acetylCoA, and CO₂ (10). This was shown by extraction of tissue samples followed by analysis using thin layer chromatography and paper chromatography with authentic samples of possible metabolites.

Animal Studies

Human Studies

[PubMed]

Myocardial oxygen consumption can be estimated with PET from analysis of the myocardial turnover rate constant (k) after administration of [¹¹C]acetate. [¹¹C]Acetate was administered to five normal volunteers and six patients with myocardial infarction. Uptake of [¹¹C]acetate by the myocardium was avid, and its clearance from the blood pool was rapid, yielding myocardial images of excellent quality. Regional k was homogeneous in the myocardiums of healthy volunteers. In patients, k in regions remote from the area of infarction was not different from values in the myocardiums of healthy human volunteers. In contrast, k in the center of the infarct region of necrotic myocardium was significantly reduced (17).

[¹¹C]Acetate PET has been shown to have high sensitivity for detection of recurrent prostate cancer and metastases. It was reported that 27 of 46 prostate cancer patients were positive with [¹¹C]acetate PET studies, whereas only eight [¹⁸F]FDG PET studies had positive detections (18). In another study, it was cautioned that acetate also accumulates in normal, hyperplastic, and benign prostate tissues. It was reported that the [¹¹C]acetate standardized uptake values for normal prostate and benign prostate, overlap significantly with those for prostate cancer patients (19).

Human dosimetry was estimated in six healthy volunteers by intravenous injection of 525 MBq (14.2 mCi) of [¹¹C]acetate (20). The organs receiving the highest absorbed doses were the pancreas (0.017 mGy/MBq or 62.9 mrad/mCi), bowel (0.011 mGy/MBq or 40.7 mrad/mCi), kidneys (0.0092 mGy/MBq or 34.0 mrad/mCi), and spleen (0.0092 mGy/MBq or 34.0 mrad/mCi). No urinary excretion of tracer was detected. The effective dose equivalent was 0.0062 mSv/MBq (22.9 mrem/mCi).

[¹¹C]Acetate is rapidly taken up by myocardium and metabolized to CO₂ and water after intravenous injection. The uptake is indirectly dependent on blood flow (21). The clearance of the tracer is a direct reflection of TCA cycle activity, which is coupled to myocardial oxygen consumption [PubMed]. Rates of clearance from myocardium of [¹¹C]acetate reflect oxidative metabolism (22). [¹¹C]Acetate PET is used to evaluate ischemia and myocardial infraction [PubMed]. Many prostate, bladder, and renal cancer patients have been imaged with [¹¹C]acetate PET to assess primary and metastatic tumors [PubMed].

NIH Support

HL13851, P30 CA91842, R24 CA83060, HL29845, HL33177, HL17646, R01 HL46895, R01 HL58408, RR00645

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