Synthesis and evaluation of radiogallium-labeled long-chain fatty acid derivatives as myocardial metabolic imaging agents

PLoS One. 2021 Dec 15;16(12):e0261226. doi: 10.1371/journal.pone.0261226. eCollection 2021.

Abstract

Since long-chain fatty acids work as the primary energy source for the myocardium, radiolabeled long-chain fatty acids play an important role as imaging agents to diagnose metabolic heart dysfunction and heart diseases. With the aim of developing radiogallium-labeled fatty acids, herein four fatty acid-based tracers, [67Ga]Ga-HBED-CC-PDA, [67Ga]Ga-HBED-CC-MHDA, [67Ga]Ga-DOTA-PDA, and [67Ga]Ga-DOTA-MHDA, which are [67Ga]Ga-HBED-CC and [67Ga]Ga-DOTA conjugated with pentadecanoic acid (PDA) and 3-methylhexadecanoic acid (MHDA), were synthesized, and their potential for myocardial metabolic imaging was evaluated. Those tracers were found to be chemically stable in 0.1 M phosphate buffered saline. Initial [67Ga]Ga-HBED-CC-PDA, [67Ga]Ga-HBED-CC-MHDA, [67Ga]Ga-DOTA-PDA, and [67Ga]Ga-DOTA-MHDA uptakes in the heart at 0.5 min postinjection were 5.01 ± 0.30%ID/g, 5.74 ± 1.02%ID/g, 5.67 ± 0.22%ID/g, and 5.29 ± 0.10%ID/g, respectively. These values were significantly lower than that of [123I]BMIPP (21.36 ± 2.73%ID/g). For their clinical application as myocardial metabolic imaging agents, further structural modifications are required to increase their uptake in the heart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Edetic Acid / analogs & derivatives
  • Edetic Acid / chemistry
  • Edetic Acid / metabolism
  • Fatty Acids / chemical synthesis*
  • Fatty Acids / pharmacology
  • Gallium / chemistry
  • Gallium Radioisotopes / chemistry
  • Gallium Radioisotopes / pharmacology*
  • Heart / diagnostic imaging*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / metabolism
  • Humans
  • Japan
  • Male
  • Mice
  • Myocardium / pathology
  • Positron-Emission Tomography / methods
  • Radioisotopes
  • Tissue Distribution
  • Tomography, X-Ray Computed / methods

Substances

  • Fatty Acids
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Radioisotopes
  • N,N'-bis(2-hydroxy-5-(ethylene-beta-carboxy)benzyl)ethylenediamine N,N'-diacetic acid
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Gallium-67
  • Edetic Acid
  • Gallium

Grants and funding

This work was supported in part by Suzuken Memorial Foundation and Kanazawa University SAKIGAKE project 2020. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.