Structure-Distribution Relationships for Metal-Labeled Myocardial Imaging Agents: Comparison of a Series of Cationic Gallium(III) Complexes with Hexadentate Bis(salicylaldimine) Ligands

Brenda W. Tsang, Carla J. Mathias, Phillip E. Fanwick, Mark A. Green

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Abstract

A series of 10 cationic gallium(III) complexes with hexadentate bis(salicylaldimine) ligands were synthesized, characterized, radiolabeled with67Ga, and screened in a rat model to assess their potential as68Ga radiopharmaceuticals for imaging the heart with positron emission tomography. The tris(salicylaldimine) ligand precursors were synthesized by condensation of either bis(3-aminopropyl)ethylenediamine (BAPEN) or bis(2,2-dimethyl-3-aminopropyl)ethylenediamine (DM-BAPEN) with 3 equiv of a salicylaldehyde derivative containing alkyl, alkoxy, or alkylamino substituents in the 4, 5, or 6 position of the aromatic ring. The cationic sixcoordinate gallium(III) bis(salicylaldimine) complexes were obtained by reaction of these tris-(salicylaldimines) with tris(acetylacetonato)gallium(III). X-ray crystallographic confirmation of the molecular structure of Ga[(4,6-(MeO)2sal)2DM-BAPEN]+I shows the Ga cation to adopt a pseudo-octahedral N4O2 coordination sphere with a trans configuration. All of the 67Ga complexes are lipophilic with measured octanol/water partition coefficients (P) varying from log P = 0.84 to 3.00. These 67Ga-labeled complexes are all found to exhibit significant myocardial uptake following intravenous administration to rats (ranging from 0.34 to 1.08% of the injected dose in myocardium at 1 min postinjection) combined with the desired myocardial retention of tracer.

Original languageEnglish (US)
Pages (from-to)4400-4406
Number of pages7
JournalJournal of Medicinal Chemistry
Volume37
Issue number25
DOIs
StatePublished - Dec 1 1994

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ethylenediamine
Gallium
Metals
Ligands
Imaging techniques
Rats
Octanols
Positron emission tomography
Radiopharmaceuticals
Molecular Structure
Intravenous Administration
Positron-Emission Tomography
Molecular structure
Cations
Condensation
Myocardium
X-Rays
Derivatives
X rays
Water

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Structure-Distribution Relationships for Metal-Labeled Myocardial Imaging Agents : Comparison of a Series of Cationic Gallium(III) Complexes with Hexadentate Bis(salicylaldimine) Ligands. / Tsang, Brenda W.; Mathias, Carla J.; Fanwick, Phillip E.; Green, Mark A.

In: Journal of Medicinal Chemistry, Vol. 37, No. 25, 01.12.1994, p. 4400-4406.

Research output: Contribution to journalArticle

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abstract = "A series of 10 cationic gallium(III) complexes with hexadentate bis(salicylaldimine) ligands were synthesized, characterized, radiolabeled with67Ga, and screened in a rat model to assess their potential as68Ga radiopharmaceuticals for imaging the heart with positron emission tomography. The tris(salicylaldimine) ligand precursors were synthesized by condensation of either bis(3-aminopropyl)ethylenediamine (BAPEN) or bis(2,2-dimethyl-3-aminopropyl)ethylenediamine (DM-BAPEN) with 3 equiv of a salicylaldehyde derivative containing alkyl, alkoxy, or alkylamino substituents in the 4, 5, or 6 position of the aromatic ring. The cationic sixcoordinate gallium(III) bis(salicylaldimine) complexes were obtained by reaction of these tris-(salicylaldimines) with tris(acetylacetonato)gallium(III). X-ray crystallographic confirmation of the molecular structure of Ga[(4,6-(MeO)2sal)2DM-BAPEN]+I− shows the Ga cation to adopt a pseudo-octahedral N4O2 coordination sphere with a trans configuration. All of the 67Ga complexes are lipophilic with measured octanol/water partition coefficients (P) varying from log P = 0.84 to 3.00. These 67Ga-labeled complexes are all found to exhibit significant myocardial uptake following intravenous administration to rats (ranging from 0.34 to 1.08{\%} of the injected dose in myocardium at 1 min postinjection) combined with the desired myocardial retention of tracer.",
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