Synthesis and biodistribution of lipophilic and monocationic gallium radiopharmaceuticals derived from N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine: potential agents for PET myocardial imaging with 68Ga

Yui May Hsiao, Carla J. Mathias, Shiaw Pyng Wey, Phillip E. Fanwick, Mark Green

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Introduction: In locations that lack nearby cyclotron facilities for radionuclide production, generator-based 68Ga radiopharmaceuticals might have clinical utility for positron emission tomography (PET) studies of myocardial perfusion and other physiological processes. Methods: The lipophilic and monocationic 67Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine) ligands the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4-methoxysalicylaldimine), bis(6-meth,oxysalicylaldimine), and bis(4,6-dimethoxysalicylaldimine) of N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine (BAPDMEN), were prepared. The structure of the unlabeled [Ga(4-MeOsal)2BAPDMEN]+PF6- salt was determined by X-ray crystallography, and the biodistribution of each of the 67Ga-labeled gallium chelates was determined in rats following intravenous administration and compared with the biodistribution of [86Rb]rubidium chloride. Results: The [Ga(4-MeOsal)2BAPDMEN]+PF6- complex exhibited the expected pseudo-octahedral N4O22- coordination sphere about the Ga3+ center with a trans disposition of the phenolate oxygen atoms. All five 67Ga radiopharmaceuticals were found to afford the desired myocardial retention of the radiogallium. The [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+ radiopharmaceutical appears to have the best properties for myocardial imaging, exhibiting 2% of the injected dose in the heart 1 min and 2 h postinjection and very high heart/nontarget ratios (heart/blood ratios of 7.6±1.0 and 54±10 at 1 and 120 min, respectively; heart/liver ratios of 1.8±0.4 and 39±3 at 1 and 120 min, respectively). Conclusions: Most of these new agents, particularly [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+, would appear superior to previously reported bis(salicylaldimine) ligands of N,N′-bis(3-aminopropyl)ethylenediamine as candidates for PET imaging of the heart with 68Ga.

Original languageEnglish (US)
Pages (from-to)39-45
Number of pages7
JournalNuclear Medicine and Biology
Volume36
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

Gallium
Radiopharmaceuticals
Positron-Emission Tomography
ethylenediamine
Radionuclide Generators
Physiological Phenomena
Ligands
Cyclotrons
X Ray Crystallography
Intravenous Administration
Perfusion
Salts
dimethylethylenediamine
Oxygen
Liver

Keywords

  • Gallium-68
  • Myocardial imaging
  • Positron emission tomography, PET
  • Radiopharmaceuticals

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

@article{aa2b9f79ae8746bab71022da44366d33,
title = "Synthesis and biodistribution of lipophilic and monocationic gallium radiopharmaceuticals derived from N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine: potential agents for PET myocardial imaging with 68Ga",
abstract = "Introduction: In locations that lack nearby cyclotron facilities for radionuclide production, generator-based 68Ga radiopharmaceuticals might have clinical utility for positron emission tomography (PET) studies of myocardial perfusion and other physiological processes. Methods: The lipophilic and monocationic 67Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine) ligands the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4-methoxysalicylaldimine), bis(6-meth,oxysalicylaldimine), and bis(4,6-dimethoxysalicylaldimine) of N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine (BAPDMEN), were prepared. The structure of the unlabeled [Ga(4-MeOsal)2BAPDMEN]+PF6- salt was determined by X-ray crystallography, and the biodistribution of each of the 67Ga-labeled gallium chelates was determined in rats following intravenous administration and compared with the biodistribution of [86Rb]rubidium chloride. Results: The [Ga(4-MeOsal)2BAPDMEN]+PF6- complex exhibited the expected pseudo-octahedral N4O22- coordination sphere about the Ga3+ center with a trans disposition of the phenolate oxygen atoms. All five 67Ga radiopharmaceuticals were found to afford the desired myocardial retention of the radiogallium. The [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+ radiopharmaceutical appears to have the best properties for myocardial imaging, exhibiting 2{\%} of the injected dose in the heart 1 min and 2 h postinjection and very high heart/nontarget ratios (heart/blood ratios of 7.6±1.0 and 54±10 at 1 and 120 min, respectively; heart/liver ratios of 1.8±0.4 and 39±3 at 1 and 120 min, respectively). Conclusions: Most of these new agents, particularly [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+, would appear superior to previously reported bis(salicylaldimine) ligands of N,N′-bis(3-aminopropyl)ethylenediamine as candidates for PET imaging of the heart with 68Ga.",
keywords = "Gallium-68, Myocardial imaging, Positron emission tomography, PET, Radiopharmaceuticals",
author = "Hsiao, {Yui May} and Mathias, {Carla J.} and Wey, {Shiaw Pyng} and Fanwick, {Phillip E.} and Mark Green",
year = "2009",
month = "1",
doi = "10.1016/j.nucmedbio.2008.10.010",
language = "English (US)",
volume = "36",
pages = "39--45",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Synthesis and biodistribution of lipophilic and monocationic gallium radiopharmaceuticals derived from N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine

T2 - potential agents for PET myocardial imaging with 68Ga

AU - Hsiao, Yui May

AU - Mathias, Carla J.

AU - Wey, Shiaw Pyng

AU - Fanwick, Phillip E.

AU - Green, Mark

PY - 2009/1

Y1 - 2009/1

N2 - Introduction: In locations that lack nearby cyclotron facilities for radionuclide production, generator-based 68Ga radiopharmaceuticals might have clinical utility for positron emission tomography (PET) studies of myocardial perfusion and other physiological processes. Methods: The lipophilic and monocationic 67Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine) ligands the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4-methoxysalicylaldimine), bis(6-meth,oxysalicylaldimine), and bis(4,6-dimethoxysalicylaldimine) of N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine (BAPDMEN), were prepared. The structure of the unlabeled [Ga(4-MeOsal)2BAPDMEN]+PF6- salt was determined by X-ray crystallography, and the biodistribution of each of the 67Ga-labeled gallium chelates was determined in rats following intravenous administration and compared with the biodistribution of [86Rb]rubidium chloride. Results: The [Ga(4-MeOsal)2BAPDMEN]+PF6- complex exhibited the expected pseudo-octahedral N4O22- coordination sphere about the Ga3+ center with a trans disposition of the phenolate oxygen atoms. All five 67Ga radiopharmaceuticals were found to afford the desired myocardial retention of the radiogallium. The [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+ radiopharmaceutical appears to have the best properties for myocardial imaging, exhibiting 2% of the injected dose in the heart 1 min and 2 h postinjection and very high heart/nontarget ratios (heart/blood ratios of 7.6±1.0 and 54±10 at 1 and 120 min, respectively; heart/liver ratios of 1.8±0.4 and 39±3 at 1 and 120 min, respectively). Conclusions: Most of these new agents, particularly [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+, would appear superior to previously reported bis(salicylaldimine) ligands of N,N′-bis(3-aminopropyl)ethylenediamine as candidates for PET imaging of the heart with 68Ga.

AB - Introduction: In locations that lack nearby cyclotron facilities for radionuclide production, generator-based 68Ga radiopharmaceuticals might have clinical utility for positron emission tomography (PET) studies of myocardial perfusion and other physiological processes. Methods: The lipophilic and monocationic 67Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine) ligands the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4-methoxysalicylaldimine), bis(6-meth,oxysalicylaldimine), and bis(4,6-dimethoxysalicylaldimine) of N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine (BAPDMEN), were prepared. The structure of the unlabeled [Ga(4-MeOsal)2BAPDMEN]+PF6- salt was determined by X-ray crystallography, and the biodistribution of each of the 67Ga-labeled gallium chelates was determined in rats following intravenous administration and compared with the biodistribution of [86Rb]rubidium chloride. Results: The [Ga(4-MeOsal)2BAPDMEN]+PF6- complex exhibited the expected pseudo-octahedral N4O22- coordination sphere about the Ga3+ center with a trans disposition of the phenolate oxygen atoms. All five 67Ga radiopharmaceuticals were found to afford the desired myocardial retention of the radiogallium. The [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+ radiopharmaceutical appears to have the best properties for myocardial imaging, exhibiting 2% of the injected dose in the heart 1 min and 2 h postinjection and very high heart/nontarget ratios (heart/blood ratios of 7.6±1.0 and 54±10 at 1 and 120 min, respectively; heart/liver ratios of 1.8±0.4 and 39±3 at 1 and 120 min, respectively). Conclusions: Most of these new agents, particularly [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+, would appear superior to previously reported bis(salicylaldimine) ligands of N,N′-bis(3-aminopropyl)ethylenediamine as candidates for PET imaging of the heart with 68Ga.

KW - Gallium-68

KW - Myocardial imaging

KW - Positron emission tomography, PET

KW - Radiopharmaceuticals

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U2 - 10.1016/j.nucmedbio.2008.10.010

DO - 10.1016/j.nucmedbio.2008.10.010

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VL - 36

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JO - Nuclear Medicine and Biology

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