Professional Drug Information > L-methyl-11CSodium Acetate Sodium Acetate C 11

Sodium Acetate C 11 (Systemic)

VA CLASSIFICATION
Primary: DX201

Another commonly used name is L-[methyl- ¹¹C]sodium acetate.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

^*Not commercially available in the U.S.

^†Not commercially available in Canada.

Category:


Diagnostic aid, radioactive (cardiac disease)—

Indications

Note: Because sodium acetate C 11 is not commercially available in the U.S. or Canada, the bracketed information and the use of the superscript 1 in this monograph reflect the lack of labeled (approved) indications for this product.

Accepted

[Cardiac imaging, positron emission tomographic]¹ and
[Myocardial infarction (diagnosis)]¹—Positron emission tomography (PET) using sodium acetate C 11 is used for the quantification of regional myocardial oxidative metabolism, which could be useful to delineate the extent and distribution of viable myocardium in patients with left ventricular dysfunction due to either acute or chronic coronary artery disease ^{{06} {07} {08} {09} {10} {13} {17} {18} {19} {20} {22}}. In addition to its use in measuring regional oxidative metabolism, sodium acetate C 11 may be used for the simultaneous evaluation of regional myocardial perfusion ^{{11} {12} {13} {15}}. It may also help to demonstrate whether thrombolytic therapy or angioplasty has improved perfusion ^{{06} {10}}.

¹ Not included in Canadian product labeling.

Physical Properties

Nuclear Data ^{01}

Radionuclide (half-life)	Mode of decay	Principal photon emissions (keV)	Mean number of emissions/ disintegration
C 11 (20.41 min)	Positron decay	Annihilation* (511)	2

^* The annihilation photons emitted in opposite directions at the moment of positron annihilation are used for imaging purposes. Detection devices usually used are positron emission tomography (PET) units; however, conventional planar scintillation cameras equipped with coincidence circuitry or high-energy collimators have been used for some studies ^{23}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Cyclotron-produced C 11-labeled carbon dioxide ( ¹¹CO ₂) may be prepared by the ¹⁴N(p,alpha) ¹¹C nuclear reaction ^{{01} {06} {08} {22}}. Acetate C 11 may be produced via carbonation of the Grignard reagent, methylmagnesium bromide, with ¹¹CO ₂ ^{{01} {06} {08}}. The radioactive adduct is hydrolyzed with water or aqueous acid ^{{01} {06} {22}}. An injectable solution of sodium acetate C 11 is obtained by resolubilization in a weakly acidic phosphate buffer and passage of this solution over a combined silver oxide-cation exchange cartridge ^{{01} {06}}.

Mechanism of action/Effect:

Cardiac disease (diagnosis)—Acetate is a substrate readily utilized by the heart ^{06}. Its radioclearance from myocardium is proportional to regional myocardial oxidative metabolism ^{23}. Acetate, like other major myocardial oxidative fuels, is oxidized to CO ₂ via the tricarboxylic acid (citric acid or Krebs) cycle ^{{06} {07} {13}}. Radiolabeled acetate enters the tricarboxylic acid cycle at the last step by binding to coenzyme A (CoA) ^{01} to form acetyl coenzyme A (acetyl-CoA) ^{{06} {07} {10} {17}}. At this level its transition through the myocardium reflects the activity of the tricarboxylic acid cycle ^{{01} {09}}. Therefore, since sodium acetate C 11 is readily oxidized via the tricarboxylic acid cycle and it is not metabolized via any other major pathways, it can be used as a tracer for the measurement of net myocardial oxygen utilization ^{{01} {06} {07}}. The oxidation of radiolabeled acetate, assessed either from the rate of ¹¹CO ₂ efflux in the venous effluent or measured externally with gamma probes, has been found to correlate closely with the rate of oxygen consumption in the myocardium ^{{06} {07}}. The oxidation of acetate and production of CO ₂ are retarded in ischemic conditions ^{06}.

In studies with rabbits, the rates of efflux of CO ₂ correlated closely with the rate of oxygen consumption in the heart ^{06}. Production of ¹¹CO ₂ resulting from oxidation of radiolabeled acetate occurred within 15 minutes after the onset of administration of the tracer and accounted for 86 ± 7% of acetate uptake ^{06}. In studies using canine myocardium, significant production of ¹¹CO ₂ does not occur for at least 4 to 4.5 minutes after initial delivery of the tracer to the myocardium. In human myocardium, the clearance of C 11 activity is much slower than in canine myocardium ^{12}.

Distribution:

C 11 activity clears rapidly from blood and rapidly accumulates in the myocardium ^{{09} {10} {11} {13}}. Radiolabeled acetate is promptly extracted by the myocardium with an extraction fraction of 30 to 50% ^{{10} {12}}. High first-pass myocardial extraction fraction under resting conditions indicates that initial uptake of radiolabeled acetate depends mainly on blood flow ^{{06} {11} {12} {17} {23}}. Radioactivity in the blood pool diminishes by 90 to 95% from peak radioactivity, usually within 2 minutes ^{10}. This rapid clearance results in good contrast between blood and myocardium ^{{06} {10} {12}}. It may also facilitate quantitative analysis of myocardial turnover rate without the need of correction for myocardial spillover from blood into the myocardium ^{10}. The evaluation of the regional distribution of early myocardial uptake of radiolabeled acetate may provide an indirect estimate of regional myocardial perfusion ^{{11} {12} {13} {15}}.

Radiolabeled acetate concentration in the myocardium reaches a plateau of about 2 to 3 minutes duration, after which C 11 activity clears from the myocardium in a monoexponential ^{{10} {12} {15} {17}} or biexponential fashion, mostly in the form of ¹¹CO ₂ ^{{11} {13}}. In contrast to the homogenous uptake and clearance observed in hearts of normal subjects, the clearance of radioactivity from the myocardium of patients with infarction has been found to be prolonged and heterogeneous ^{10}. Uptake and clearance of radiolabeled acetate in the zones of infarction were found to be decreased, which may indicate lessening in regional myocardial blood flow and/or oxygen consumption ^{{10} {17} {18} {19}}. Regions immediately adjacent to the infarct zone also had reduced myocardial oxygen consumption in comparison with those regions farther away from the infarct ^{10}.

Tissue kinetics of radiolabeled acetate are insensitive to the presence of alternate substrates in the myocardium (e.g., lactate, glucose) ^{{07} {09} {10} {16} {17}}.

Also, sodium acetate C 11 has high accumulation in the normal pancreas, with peak activity reached by about 5 minutes, and only one third of peak activity lost by 30 minutes ^{14}.

Biotransformation:

Metabolism of acetate after its activation to acetyl coenzyme A (CoA) is predominantly via mitochondrial oxidation ^{{06} {10}}. Metabolites include ketones (e.g., beta-hydroxybutyrate and acetoacetate), citrate, succinate, and lactate ^{{06} {15}}. In animal studies, 80 to 90% of the radiolabeled acetate extracted by the myocardium was oxidized, and less than 0.1% of acetate was incorporated into tissue lipid ^{{06} {07}}.

Half-life:

Clearance of C 11 radioactivity from myocardium—10.5 minutes (in normal myocardium) ^{{06} {11}}.

Note: Clearance of C 11 radioactivity from myocardium is linearly related to oxygen consumption ^{{09} {15} {18} {19} {20}}. Clearance rates, and consequently the decline of radiolabeled acetate concentration, are slower in ischemic tissue relative to those in normal tissue because of the higher rates of oxidative metabolism in normal myocardium ^{{07} {11} {18} {19}}.


Time to peak diagnostic effect

Myocardial peak activity (when regional activity is proportional to blood flow)—Occurs 4 minutes after tracer administration ^{{11} {17}}. Measuring the rate of clearance over the next 20 to 30 minutes provides desired diagnostic information about myocardial viability ^{17}.

Radiation dosimetry:
^{03}

Estimated absorbed radiation dose*
Organ	mGy/MBq (mean)	rad/mCi
Heart wall	0.1	0.37
Lungs	0.02	0.07
Thymus	0.005	0.02
Pancreas	0.004	0.01
Adrenals	0.003	0.01
Breasts	0.003	0.01
Gallbladder wall	0.003	0.01
Stomach	0.003	0.01
Liver	0.003	0.01
Red marrow	0.003	0.01
Spleen	0.003	0.01
Large intestine wall, lower	0.002	0.007
Small intestine	0.002	0.007
Large intestine wall, upper	0.002	0.007
Kidneys	0.002	0.007
Muscle	0.002	0.007
Ovaries	0.002	0.007
Bone Surface	0.002	0.007
Skin	0.002	0.007
Testes	0.002	0.007
Thyroid	0.002	0.007
Urinary bladder wall	0.002	0.007
Uterus	0.002	0.007
Total body	0.003	0.01
Effective dose: 0.005 mSv/MBq (0.02 rem/mCi)

^* For adults; intravenous injection ^{03}. Data based on the Radiopharmaceutical Internal Dose Information Center, July 1995. Oak Ridge Institute for Science and Education.


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Studies to assess transplacental transfer of sodium acetate C 11 have not been done in humans. The possibility of pregnancy should be assessed in women of childbearing potential. Clinical situations exist where the benefit to the patient and fetus, based on information derived from radiopharmaceutical use, outweighs the risks from fetal exposure to radiation. In this situation, the physician should use discretion and reduce the administered activity to the lowest practical amount. ^{{04} {17}}

Breast-feeding

It is not known whether sodium acetate C 11 is distributed into breast milk. However, due to the short physical half-life of sodium acetate C 11 ^{01}, any excretion of this agent during lactation is unlikely to result in significant radiation exposure to the breast-feeding infant. Radiation-absorbed dose to breast-feeding infant will be negligible after waiting 2 hours ^{23}.

Pediatrics

Appropriate studies on the relationship of age to the effects of sodium acetate C 11 have not been performed in children. However, pediatrics-specific problems that would limit the usefulness of sodium acetate C 11 in children are not expected ^{17}.


Geriatrics


Appropriate studies on the relationship of age to the effects of sodium acetate C 11 have not been performed in the geriatric population. However, studies that included older patients were conducted, and geriatrics-specific problems that would limit the usefulness of this agent in the elderly are not expected ^{{10} {11} {12} {14} {19} {20} {21} {22}}.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problem exists
Sensitivity to the radiopharmaceutical preparation


Side/Adverse Effects
There are no known side/adverse effects associated with the use of sodium acetate C 11 ^{{10} {11}}.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Radiopharmaceuticals (Diagnostic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Action in the body: Myocardial accumulation and clearance of radiolabeled acetate may be measured externally

Small amounts of radioactivity used in diagnosis; radiation received is low and considered safe

Before having this test
»   Conditions affecting use, especially:
Sensitivity to the radiopharmaceutical preparation

Pregnancy—Risk to fetus from radiation exposure as opposed to benefit derived from use should be considered

Preparation for this test
Nuclear medicine department should advise patient on any preparatory instructions

Precautions after having this test
No special precautions needed


General Dosing Information
Radiopharmaceuticals are to be administered only by or under the supervision of physicians who have had extensive training in the safe use and handling of radioactive materials and who are authorized by the appropriate federal or state regulatory agency, if required, or, outside the U.S., the appropriate authority ^{05}.

Positron emission tomography (PET) images of C 11 accumulation in the myocardium are acquired over 120 seconds, and serially thereafter for up to 30 minutes ^{{10} {12} {15} {17}}, beginning 60 seconds after the administration of sodium acetate C 11 ^{{06} {11} {12}}. Waiting 60 seconds before initiating PET imaging allows for adequate clearance of C 11 activity from the blood pool ^{{12} {17}}.

Early PET images show regional net myocardial uptake of sodium acetate C 11, which reflects regional myocardial perfusion ^{{12} {17}}. Later serial images show regional rates of myocardial clearance, which reflects regional oxidative metabolism and oxygen consumption ^{{12} {17} {18} {19}}.

Safety considerations for handling this radiopharmaceutical
Guidelines for the receipt, storage, handling, dispensing, and disposal of radioactive materials are available from scientific, professional, state, federal, and international bodies. Handling of this radiopharmaceutical should be limited to those individuals who are appropriately qualified and authorized. ^{02}


Parenteral Dosage Forms

SODIUM ACETATE C 11 INJECTION USP

Note: Because sodium acetate C 11 is not commercially available in the U.S. or Canada, the bracketed information and the use of the superscript 1 in this monograph reflect the lack of labeled (approved) indications for this product.


Usual adult and adolescent administered activity
[Cardiac imaging]¹
Intravenous, 9.25 to 14.8 megabecquerels (0.25 to 0.4 millicurie) per kg of body weight administered as a single injection over thirty seconds ^{{06} {10} {11} {12} {13} {18} {19} {20}}.


Usual pediatric administered activity
Safety and efficacy have not been established.

Usual geriatric administered activity
See Usual adult and adolescent administered activity

Strength(s) usually available
U.S.—
Prepared on-site at various clinical facilities.

Canada—
Prepared on-site at various clinical facilities.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F) ^{01}. Unless specified by the supplier, it is prudent to avoid extreme temperatures ^{23}.

Stability:
Preparations of sodium acetate C 11 containing up to 2 gigabecquerels (54 millicuries) per 5 mL have been shown to be stable in aqueous solutions at pH levels between 5 and 7.5 for 2 hours at room temperature ^{01}.


Caution:
Radioactive material.

Developed: 06/08/1999

References

1. Stöcklin G, Pike VW, editors. Radiopharmaceuticals for positron emission tomography: methodological aspects. Boston: Kluwer Academic Publishers; 1993. p. 98, 100.
   

2. Radiopharmaceuticals Advisory Panel Meeting, 4/96.
   

3. Radiation Internal Dose Information Center. Oak Ridge Institute for Science and Education. Oak Ridge, TN.
   

4. Radiopharmaceuticals Advisory Panel Meeting, 5/8/91.
   

5. Radiopharmaceuticals Advisory Panel Meeting, 8/4/92.
   

6. Brown M, Marshall DR, Sobel BE, et al. Delineation of myocardial oxygen utilization with carbon-11-labeled acetate. Circulation 1987 Sep; 76(3): 687-96.
   

7. Buxton DB, Schwaiger M, Nguyen A, et al. Radiolabeled acetate as a tracer of myocardial tricarboxylic acid cycle flux. Circ Res 1988 Sep; 63(3): 628-34.
   

8. Pike VW, Eakins MN, Allan RM, et al. Preparation of [1- ¹¹C]acetate: an agent for the study of myocardial metabolism by positron emission tomography. Int J Appl Radiat Isot 1982 Jul; 33(7): 505-12.
   

9. Buxton DB, Nienaber CA, Luxen A, et al. Noninvasive quantitation of regional myocardial oxygen consumption in vivo with [1-11C]acetate and dynamic positron emission tomography. Circulation 1989 Jan; 79(1): 134-42.
   

10. Walsh MN, Geltman EM, Brown MA, et al. Noninvasive estimation of regional myocardial oxygen consumption by positron emission tomography with carbon-11 acetate in patients with myocardial infarction. J Nucl Med 1989 Nov; 30(11): 1798-808.
    

11. Chan SY, Brunken RC, Phelps ME, et al. Use of the metabolic tracer carbon-11-acetate for evaluation of regional myocardial perfusion. J Nucl Med 1991 Apr; 32(4): 665-72.
    

12. Gropler RJ, Siegel BA, Geltman EM, et al. Myocardial uptake of carbon-11-acetate as an indirect estimate of regional myocardial blood flow. J Nucl Med 1991; 32: 245-51.
    

13. Krivokapich J, Huang S, Schelbert H. Assessment of the effects of dobutamine on myocardial blood flow and oxidative metabolism in normal human subjects using nitrogen-13 ammonia and carbon-11 acetate. Am J Cardiol 1993 June; 71: 1351-6.
    

14. Shreve PD, Gross MD. Imaging of the pancreas and related disease with PET carbon-11-acetate. J Nucl Med 1997 Aug; 38(8): 1305-10.
    

15. Sun KT, Yeatman LS, Buxton DB, et al. Simultaneous measurement of myocardial oxygen consumption and blood flow using [1-carbon-11]acetate. J Nucl Med 1998 Feb; 39(2): 272-80.
    

16. Armbrecht JJ, Buxton DB, Brunken RC, et al. Regional myocardial oxygen consumption determined noninvasively in humans with [1-11C]acetate and dynamic positron tomography. Circulation 1989 Oct; 80(4): 863-72.
    

17. Reviewers` comments per monograph revision of 8/12/98.
    

18. Gropler RJ, Geltman EM, Sampathkumaran K, et al. Functional recovery after coronary revascularization for chronic coronary artery disease is dependent on maintenance of oxidative metabolism. J Am Coll Cardiol 1992; 20(3): 569-77.
    

19. Gropler RJ, Siegel BA, Sampathkumaran K, et al. Dependence of recovery of contractile function on maintenance of oxidative metabolism after myocardial infarction. J Am Coll Cardiol 1992; 19(5): 989-97.
    

20. Gropler RJ, Geltman EM, Sampathkumaran K, et al. Comparison of carbon-11-acetate with fluorine-18-fluorodeoxyglucose for delineating viable myocardium by positron emission tomography. J Am Coll Cardiol 1993; 22(6): 1587-97.
    

21. Rubin PJ, Lee DS, Dávila-Román VG, et al. Superiority of C-11 acetate compared with F-18 fluorodeoxyglucose in predicting myocardial functional recovery by positron emission tomography in patients with acute myocardial infarction. Am J Cardiol 1996 Dec; 78: 1230-6.
    

22. Hata T, Nohara R, Masatoshi F, et al. Noninvasive assessment of myocardial viability by positron emission tomography with C-11 acetate in patients with old myocardial infarction: usefulness of low-dose dobutamine infusion. Circulation 1996; 94(8): 1834-41.
    

23. Advisory Panel consensus per 10/28/98 meeting.
    

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