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

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 - 1993
Externally publishedYes

Fingerprint

Gallium
Ligands
Ethane
Intravenous Injections
Octanols
Crystallography
Ethanol
Carbon
X-Rays
Dogs
Water

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Potential gallium-68 tracers for imaging the heart with PET : Evaluation of four gallium complexes with functionalized tripodal tris(salicylaldimine) ligands. / Green, Mark; Mathias, C. J.; Neumann, W. L.; Fanwick, P. E.; Janik, M.; Deutsch, E. A.

In: Journal of Nuclear Medicine, Vol. 34, No. 2, 1993, p. 228-233.

Research output: Contribution to journalArticle

@article{0c35c7c31fb64d7986acaf151aaf4857,
title = "Potential gallium-68 tracers for imaging the heart with PET: Evaluation of four gallium complexes with functionalized tripodal tris(salicylaldimine) ligands",
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].",
author = "Mark Green and Mathias, {C. J.} and Neumann, {W. L.} and Fanwick, {P. E.} and M. Janik and Deutsch, {E. A.}",
year = "1993",
language = "English (US)",
volume = "34",
pages = "228--233",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "2",

}

TY - JOUR

T1 - Potential gallium-68 tracers for imaging the heart with PET

T2 - Evaluation of four gallium complexes with functionalized tripodal tris(salicylaldimine) ligands

AU - Green, Mark

AU - Mathias, C. J.

AU - Neumann, W. L.

AU - Fanwick, P. E.

AU - Janik, M.

AU - Deutsch, E. A.

PY - 1993

Y1 - 1993

N2 - 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].

AB - 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].

UR - http://www.scopus.com/inward/record.url?scp=0027466103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027466103&partnerID=8YFLogxK

M3 - Article

C2 - 8429341

AN - SCOPUS:0027466103

VL - 34

SP - 228

EP - 233

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 2

ER -