Skip to main content
SpringerLink
Log in

Synthesis and biological evaluation of fatty acids containing 99mTc-oxo and 99mTc-nitrido for myocardial metabolism imaging

  • Published:
Journal of Radioanalytical and Nuclear Chemistry Aims and scope Submit manuscript

Abstract

In this study, four 99mTc-labeled fatty acid analogues including [99mTcO]3+ and [99mTc≡N]2+ cores were successfully synthesized and fully characterized. The radiochemical purity of those compounds was over 90 % and they were stable when incubated in a rat serum for 3 h at 37 °C. The biodistribution studies in mice demonstrated that compounds labeled with [99mTcO]3+ exhibited good uptakes (6.11 %ID/g of [99mTcO]-MAMA-DTA and 3.89 %ID/g of [99mTcO]-MAMA-UTA at 1 min postinjection) and the maximum heart to blood ratio was 5.91 at 30 min postinjection of [99mTcO]-MAMA-DTA. While the others labeled with [99mTc≡N]2+ showed lower uptakes and faster washout from the myocardium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Scheme 2
Fig. 1

Similar content being viewed by others

Abbreviations

ATP:

Adenosine triphosphate

PET:

Positron emission tomography

SPECT:

Single-photon emission computed tomography

IPPA:

123I-iodophenylpentadecanoic acid

BMIPP:

15-(p-[123I]iodophenyl)-3-methylpentadecanoic acid

SDH:

Succinic dihydrazide

GH:

Glucoheptonate

[99mTc]-MAMA-HDA:

[99mTc]-MAMA-hexadecanoic acid

[99mTcO]-MAMA-DTA (1):

[99mTcO]-MAMA-decanoyl thiophenepropanoic acid

[99mTcO]-MAMA-UTA (2):

[99mTcO]-MAMA-undecanoyl thiophenepropanoic acid

[99mTc≡N]-MAMA-DTA (3):

[99mTc≡N]-MAMA-decanoyl thiophenepropanoic acid

[99mTc≡N]-MAMA-UTA (4):

[99mTc≡N]-MAMA-undecanoyl thiophenepropanoic acid

References

  1. Van der Vusse GJ, Glatz JF, Stam HC, Reneman RS (1992) Fatty acid homeostasis in the normoxic and ischemic heart. Physiol Rev 72(4):881–940

    Google Scholar 

  2. Neely JR, Rovetto MJ, Oram JF (1972) Myocardial utilization of carbohydrate and lipids. Prog Cardiovasc Dis 15:289–329

    Article  CAS  Google Scholar 

  3. Brinkmann JFF, Abumrad NA, Ibrahimi A, Van der Vusse GJ, Glatz JFC (2002) New insights into long-chain fatty acid uptake by heart muscle: a crucial role for fatty acid translocase/CD36. Biochem J 367:561–570

    Article  CAS  Google Scholar 

  4. Liepinsh E, Makrecka M, Kuka J, Makarova E, Vilskersts R, Cirule H, Sevostjanovs E, Grinberga S, Pugovics O, Dambrova M (2014) The heart is better protected against myocardial infarction in the fed state compared to the fasted state. Metabolism 63:127–136

    Article  CAS  Google Scholar 

  5. Maria ARR, Lawrence S, Maressa JV, Elizabeth JP (2012) Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity. Metabolism 61(2):202–212

    Article  Google Scholar 

  6. Viscarra JA, Ortiz RM (2013) Cellular mechanisms regulating fuel metabolism in mammals: role of adipose tissue and lipids during prolonged food deprivation. Metabolism 62(7):889–897

    Article  CAS  Google Scholar 

  7. Lee BC, Kim DH, Lee I, Choe YS, Chi DY, Lee KH, Choi Y, Kim BT (2008) 16-Cyclopentadienyl tricarbonyl 99mTc 16-Oxo-hexadecanoic acid: synthesis and evaluation of fatty acid metabolism in mouse myocardium. J Med Chem 51:3630–3634

    Article  CAS  Google Scholar 

  8. Palaniswamy SS, Padma S (2011) Cardiac fatty acid metabolism and ischemic memory imaging with nuclear medicine techniques. Nucl Med Commun 32:672–677

    Article  CAS  Google Scholar 

  9. Tamaki N, Morita K, Kuge Y, Tsukamoto E (2000) The role of fatty acids in cardiac imaging. J Nucl Med 41:1525–1534

    CAS  Google Scholar 

  10. Lerch R, Bergmann SR, Ambos HD, Welch MJ, Ter-Pogossian MM, Sobel BE (1982) Effect of flow independent reduction of metabolism on regional myocardial clearance of 11C-palmitate. Circulation 65:731–738

    Article  CAS  Google Scholar 

  11. Wyns W, Schwaiger M, Huang SC, Buxton DB, Hansen H, Selin C, Keen R, Phelps ME (1989) Effects of inhibition of fatty acid oxidation on myocardial kinetics of 11C-palmitate. J Circ Res 65:1787–1797

    Article  CAS  Google Scholar 

  12. Tamaki N, Kawamoto M, Yonekura Y, Fujibayashi Y, Takahashi N, Konishi J, Nohara R, Kambara H, Kawai C, Ikekubo K (1992) Regional metabolic abnormality in relation to perfusion and wall motion in patients with myocardial infarction: assessment with emission tomography using an iodinated branched fatty acid analog. J Nucl Med 33:659–667

    CAS  Google Scholar 

  13. Zeng HH, Zhang HB (2014) Synthesis and biological evaluation of fatty acids conjugates bearing cyclopentadienyl-donors incorporated [99mTc/Re(CO)3]+ for myocardical imaging. Eur J Med Chem 72:10–17

    Article  CAS  Google Scholar 

  14. Magata Y, Kawaguchi T, Ukon M, Yamamura N, Uehara T, Ogawa K, Arano Y, Temma T, Mukai T, Tadamura E, Saji H (2004) A Tc-99m-labeled long chain fatty acid derivative for myocardial imaging. Bioconjugate Chem 15:389–393

    Article  CAS  Google Scholar 

  15. O’Neil JP, Wilson SR, Katzenellenbogen JA (1994) Preparation and structural characterization of monoamine-monoamide bis(thiol) oxo complexes of Technetium(V) and Rhenium(V). Inorg Chem 33:319–323

    Article  Google Scholar 

  16. Lu J, Kong DJ, Yang Z, Yang SY, Fan WW, Jia HM, Wang XB (2007) Preparation of 99mTc-nitrido asymmetrical heterocomplex with 4-(cyclohexylpiperazin- 1-yl)-dithioformate and its biological evaluation as a potential myocardial imaging agent. Apply Radiat and Isotopes. 65:1134–1139

    Article  CAS  Google Scholar 

  17. Mathur A, Subramanian S, Mallia MB, Banerjee S, Samuel G, Sarma HD, Venkatesh M (2008) Synthesis and bio-evaluation of a new fatty acid derivative for myocardial imaging. Bioorgan Med Chem. 16:7927–7931

    Article  CAS  Google Scholar 

  18. Cazzola E, Benini E, Pasquali M, Mirtschink P, Walther M, Pietzsch HJ (2008) Labeling of fatty acid ligands with the strong electrophilic metal fragment [99mTc(N)(PNP)]2+ (PNP = diphosphane ligand). Bioconjugate Chem 19:450–460

    Article  CAS  Google Scholar 

  19. Uehara T, Uemura T, Hirabayashi S, Adachi S, Odaka K, Akizawa H, Magata Y, Irie T, Arano Y (2007) Technetium-99m-labeled long chain fatty acid analogues metabolized by β-oxidation in the heart. J Med Chem 50:543–549

    Article  CAS  Google Scholar 

  20. Heintz AC, Jung CM, Stehr SN, Mirtschink P, Walther M, Pietzsch J, Bergmann R, Pietzsch HJ, Spies H, Wunderlich G, Kropp J, Deussen A (2007) Myocardial uptake and biodistribution of newly designed technetium-labelled fatty acid analogues. Nucl Med Commun 28:637–645

    Article  CAS  Google Scholar 

  21. Larock RC, Leach DR, Bjorge SM (1986) Synthesis of bicyclic and tricyclic prostanoic acids and thiophene-containing prostaglandin endoperoxide analogues via thienylpalladation of bicyclic alkenes. J Org Chem 51:5221–5226

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledged the Significant New Drugs Development (Grant No. 2014ZX09507007-001), Natural Science Foundation of China (No. 21371026) and Science and Technology Support Program (No. 2014BAA03B03) for financial support.

Author information

Authors and Affiliations

  1. Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, No. 19, XinJieKouWai St., HaiDian District, Beijing, 100875, People’s Republic of China

    Xiang Li, Aiqin Wu, Qianqian Xue, Yu Fang, Jianping Liu, Huabei Zhang & Huaying Bao

Authors
  1. Xiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aiqin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qianqian Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jianping Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Huabei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Huaying Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Huabei Zhang or Huaying Bao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Wu, A., Xue, Q. et al. Synthesis and biological evaluation of fatty acids containing 99mTc-oxo and 99mTc-nitrido for myocardial metabolism imaging. J Radioanal Nucl Chem 307, 1429–1438 (2016). https://doi.org/10.1007/s10967-015-4232-0

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-015-4232-0

Keywords

Search

Navigation