Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-09-2009 | Original Article

[¹⁸F]Fluoroacetate is not a functional analogue of [¹¹C]acetate in normal physiology

Authors: Örjan Lindhe, Aijun Sun, Johan Ulin, Obaidur Rahman, Bengt Långström, Jens Sörensen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2009

Abstract

Purpose

[¹¹C]Acetate (C-AC) is a general PET tracer of cellular carbon flux and useful for clinical imaging in heart disease as well as prostate cancer and other tumours. C-AC has a high (70%) whole-body extraction fraction, proportional to blood flow in many organs. Trapping is related to organ-specific enzymatic activation and formation of [¹¹C]-acetyl-CoA, the fate of which has been well characterized. Due to the logistic challenges with C-AC, 2-[¹⁸F]fluoroacetate (F-AC) has been proposed as a marker for prostate cancer imaging.

Method

We evaluated the potential of F-AC as a tracer for imaging blood flow and early enzymatic steps in the intermediary metabolism. C-AC and F-AC were injected serially in three cynomolgus monkeys and one domestic pig and scanned using PET/CT. A dynamic scan covering heart and liver was followed by repeated whole-body imaging. Kinetic patterns were compared for the myocardium, liver, blood and other organs.

Results

C-AC kinetics and organ distribution in both species were similar to those previously established in man. In contrast, F-AC showed prolonged blood retention, no detectable trapping in myocardium or salivary glands, rapid clearance from liver and extensive excretion to bile and urine. Massive defluorination was seen in the pig, resulting in intense skeletal activity.

Conclusion

2-[¹⁸F]Fluoroacetate cannot be regarded as a functional analogue of 1-[¹¹C]acetate in normal physiology and appears to be of little use for studies of organ blood flow, intermediary metabolism or lipid synthesis.

Available only for authorised users

Hara T, Kondo T, Hara T, Kosaka N. Use of 18F-choline and 11C-choline as contrast agents in positron emission tomography imaging-guided stereotactic biopsy sampling of gliomas. J Neurosurg 2003;99(3):474–9PubMedCrossRef

Ishiwata K, Kawamura K, Wang WF, Furumoto S, Kubota K, Pascali C, et al. Evaluation of O-[11C]methyl-L-tyrosine and O-[18F]fluoromethyl-L-tyrosine as tumor imaging tracers by PET. Nucl Med Biol 2004;31(2):191–8. doi:10.1016/j.nucmedbio.2003.07.004 PubMedCrossRef

Krohn KA, Mankoff DA, Eary JF. Imaging cellular proliferation as a measure of response to therapy. J Clin Pharmacol 2001;Suppl:96S–103S.

Vander Borght T, Pauwels S, Lambotte L, Labar D, De Maeght S, Stroobandt G, et al. Brain tumor imaging with PET and 2-[carbon-11]thymidine. J Nucl Med 1994;35(6):974–82PubMed

Krebs HA The tricarboxylic acid cycle. Harvey Lect 1948;Series 44:165–99PubMed

Yoshimoto M, Waki A, Yonekura Y, Sadato N, Murata T, Omata N, et al. Characterization of acetate metabolism in tumor cells in relation to cell proliferation: acetate metabolism in tumor cells. Nucl Med Biol 2001;28(2):117–22. doi:10.1016/S0969-8051(00)00195-5 PubMedCrossRef

Mittendorfer B, Sidossis LS, Walser E, Chinkes DL, Wolfe RR. Regional acetate kinetics and oxidation in human volunteers. Am J Physiol 1998;274(6 Pt 1):E978–83PubMed

Sörensen J, Andrén B, Blomquist G, Ståhle E, Långström B, Heidenstierna G. The central circulation in congestive heart failure non-invasively evaluated with dynamic positron emission tomography. Clin Physiol Funct Imaging 2006;26(3):171–7. doi:10.1111/j.1475-097X.2006.00670.x PubMedCrossRef

Chen S, Ho C, Feng D, Chi Z. Tracer kinetic modeling of 11C-acetate applied in the liver with positron emission tomography. IEEE Trans Med Imaging 2004;23(4):426–32. doi:10.1109/TMI.2004.824229 PubMedCrossRef

10.

Luong A, Hannah VC, Brown MS, Goldstein JL. Molecular characterization of human acetyl-CoA synthetase, an enzyme regulated by sterol regulatory element-binding proteins. J Biol Chem 2000;275(34):26458–66. doi:10.1074/jbc.M004160200 PubMedCrossRef

11.

Fujino T, Kondo J, Ishikawa M, Morikawa K, Yamamoto TT. Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate. J Biol Chem 2001;276(14):11420–6. doi:10.1074/jbc.M008782200 PubMedCrossRef

12.

Rigo P, de Landsheere C, Melon P, Kulbertus H. Imaging of myocardial metabolism by positron emission tomography. Cardiovasc Drugs Ther 1990;4(Suppl 4):847–51. doi:10.1007/BF00051291 PubMedCrossRef

13.

Sun A, Sörensen J, Karlsson M, Turesson I, Langström B, Nilsson P, et al. 1-[11C]-acetate PET imaging in head and neck cancer—a comparison with 18F-FDG-PET: implications for staging and radiotherapy planning. Eur J Nucl Med Mol Imaging 2007;34(5):651–7. doi:10.1007/s00259-006-0298-9 PubMedCrossRef

14.

Soloviev D, Fini A, Chierichetti F, Al-Nahhas A, Rubello D. PET imaging with 11C-acetate in prostate cancer: a biochemical, radiochemical and clinical perspective. Eur J Nucl Med Mol Imaging 2008;35(5):942–9. doi:10.1007/s00259-007-0662-4 PubMedCrossRef

15.

Oyama N, Akino H, Kanamaru H, Suzuki Y, Muramoto S, Yonekura Y, et al. 11C-acetate PET imaging of prostate cancer. J Nucl Med 2002;43(2):181–6PubMed

16.

Oyama N, Miller TR, Dehdashti F, Siegel BA, Fischer KC, Michalski JM, et al. 11C-acetate PET imaging of prostate cancer: detection of recurrent disease at PSA relapse. J Nucl Med 2003;44(4):549–55PubMed

17.

Matthies A, Ezziddin S, Ulrich EM, Palmedo H, Biersack HJ, Bender H, et al. Imaging of prostate cancer metastases with 18F-fluoroacetate using PET/CT. Eur J Nucl Med Mol Imaging 2004;31(5):797. doi:10.1007/s00259-003-1437-1 PubMedCrossRef

18.

Nanni C, Castellucci P, Farsad M, Rubello D, Fanti S. 11C/18F-choline PET or 11C/18F-acetate PET in prostate cancer: may a choice be recommended? Eur J Nucl Med Mol Imaging 2007;34(10):1704–5. doi:10.1007/s00259-007-0491-5 PubMedCrossRef

19.

Ponde DE, Dence CS, Oyama N, Kim J, Tai YC, Laforest R, et al. 18F-fluoroacetate: a potential acetate analog for prostate tumor imaging—in vivo evaluation of 18F-fluoroacetate versus 11C-acetate. J Nucl Med 2007;48(3):420–8PubMed

20.

Goncharov NV, Jenkins RO, Radilov AS. Toxicology of fluoroacetate: a review, with possible directions for therapy research. J Appl Toxicol 2006;26(2):148–61. doi:10.1002/jat.1118 PubMedCrossRef

21.

Sykes TR, Ruth TJ, Adam MJ. Synthesis and murine tissue uptake of sodium [18F]fluoroacetate. Int J Rad Appl Instrum B 1986;13(5):497–500. doi:10.1016/0883-2897(86)90126-1 PubMed

22.

Kihlberg T, Valind S, Långström B. Synthesis of [1-11C], [2-11C], [1-11C](2H3) and [2-11C](2H3)acetate for in vivo studies of myocardium using PET. Nucl Med Biol 1994;21(8):1067–72. doi:10.1016/0969-8051(94)90178-3 PubMedCrossRef

23.

Tang D, Li HJ, Chen J, Guo CW, Li P. Rapid and simple method for screening of natural antioxidants from Chinese herb Flos Lonicerae Japonicae by DPPH-HPLC-DAD-TOF/MS. J Sep Sci 2008;31(20):3519–26. doi:10.1002/jssc.200800173 PubMedCrossRef

24.

Jeong JM, Lee DS, Chung JK, Lee MC, Koh CS, Kang SS. Synthesis of no-carrier-added [18F]fluoroacetate. J Labelled Comp Radiopharm 1997;39(5):395–9. doi:10.1002/(SICI)1099-1344(199705)39:5<395::AID-JLCR985>3.0.CO;2-4 CrossRef

25.

van den Hoff J, Burchert W, Börner AR, Fricke H, Kühnel G, Meyer GJ, et al. [1-11C]Acetate as a quantitative perfusion tracer in myocardial PET. J Nucl Med 2001;42(8):1174–82PubMed

26.

Dienel GA, Popp D, Drew PD, Ball K, Krisht A, Cruz NF. Preferential labeling of glial and meningial brain tumors with [2-(14)C]acetate. J Nucl Med 2001;42(8):1243–50PubMed

27.

Hosoi R, Kashiwagi Y, Tokumura M, Abe K, Hatazawa J, Inoue O. Sensitive reduction in 14C-acetate uptake in a short-term ischemic rat brain. J Stroke Cerebrovasc Dis 2007;16(2):77–81. doi:10.1016/j.jstrokecerebrovasdis.2006.11.005 PubMedCrossRef

Title: [18F]Fluoroacetate is not a functional analogue of [11C]acetate in normal physiology
Authors: Örjan Lindhe
Aijun Sun
Johan Ulin
Obaidur Rahman
Bengt Långström
Jens Sörensen
Publication date: 01-09-2009
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2009
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-009-1128-7

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

[¹⁸F]Fluoroacetate is not a functional analogue of [¹¹C]acetate in normal physiology

Abstract

Purpose

Method

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Method

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 9/2009

Eugene C. Lin, Edward J. Escott, Kavita D. Garg, Andrew G. Bleicher, David Alexander: Practical differential diagnosis for CT and MRI

Validation of sentinel lymph node dissection in prostate cancer: experience in more than 2,000 patients

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with 99mTc- and 123I-labelled probes

The influence of Bz-DOTA and CHX-A″-DTPA on the biodistribution of ABD-fused anti-HER2 Affibody molecules: implications for 114mIn-mediated targeting therapy

18F-Fluoroglucosylation of peptides, exemplified on cyclo(RGDfK)

Incidental head and neck 18F-FDG uptake on PET/CT without corresponding morphological lesion: early predictor of cancer development?