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

VL - 34

SP - 228

EP - 233

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 2

ER -