Potential gallium-68 tracers for imaging the heart with PET: Evaluation of four gallium complexes with functionalized tripodal tris(salicylaldimine) ligands

M. A. Green, C. J. Mathias, W. L. Neumann, P. E. Fanwick, M. Janik, E. A. Deutsch

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Abstract

Gallium-67 and 68Ga complexes have been synthesized with tripodal hexadentate salicylaldimine ligands derived from 1,1,1- tris(salicylaldiminomethyl)ethane, sal3tame. The four ligands evaluated contained alkoxy substituents (n-BuO-, iso-BuO-, sec-BuO-, and n-PrO-) on the terminal ethane carbon of the ligand backbone. In the case of the n-PrO- derivative, the tris(salicylaldimine) ligand was additionally substituted with methoxy groups in the 5-position of the aromatic rings. The 67Ga and 68Ga-complexes of these ligands were prepared by ligand exchange from 67Ga- or 68Ga-acetylacetonate in ethanol. The nonradioactive Ga[(sal)3tame-O-iso-Bu] complex was similarly prepared and shown by x-ray crystallography to exhibit the expected pseudo-octahedral N3O33- coordination sphere about the Ga3+ center. These Ga-radiotracers are highly lipophilic, as demonstrated by their octanol/water partition coefficients. Log P values of 3.1, 3.1, 2.6, and 2.5 were found for the [(sal)3tame-O- iso-Bu], [(sal)3tame-O-n-Bu], [(sal)3tame-O-sec-Bu], and [(5- MeOsal)3tame-O-n-Pr] complexes, respectively. Following intravenous injection into rats, these complexes are rapidly cleared from the blood and exhibit significant myocardial uptake. At 1 min postinjection, 2.4%, 2.0%, 2.1% and 1.1% of the injected dose was found in the heart for the iso-BuO, n- BuO, sec-BuO, and n-PrO complexes, respectively, dropping to 1.0%, 0.8%, 0.8%, and 0.7% at 5 min. The corresponding heart-to-blood ratios are quite high: 17 ± 3, 14 ± 2, 12 ± 2 and 3.5 ± 0.4 at 1 min and 14 ± 4, 10 ± 1, 10 ± 1 and 3.2 ± 0.1 at 5 min postinjection. High quality myocardial images were obtained with PET in a normal dog using data collected from 2 to 10 min following intravenous injection of 68Ga[(sal)3tame-O-iso-Bu].

Original languageEnglish (US)
Pages (from-to)228-233
Number of pages6
JournalJournal of Nuclear Medicine
Volume34
Issue number2
StatePublished - Jan 1 1993

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ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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