In vitro and in vivo characterization of 67Ga3+ complexes with cis,cis-1,3,5-triamino-cyclohexane-N,N′,N″-triacetic acid derivatives

E. Dadachova, C. Park, N. Eberly, D. Ma, C. H. Paik, M. W. Brechbiel

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The aim of this study was to investigate the in vitro and in vivo performance of a 67Ga complex with cis,cis-1,3,5-triaminocyclohexane-N,N′,N″-triacetic acid (tachta) as a potential ligand for use as a Ga(III) radiopharmaceutical for PET imaging. The radiolabeling procedure, electrophoretic properties, lipophilicity, acid stability, human serum stability and biodistribution in mice of 67Ga(tachta) were investigated. The 67Ga(tachta) complex forms at 10-3 M tachta concentration at 40°C in 100% yield; it is neutral, non-lipophilic, 90% stable at pH = 4 and 5 and 100% stable at pH = 6, for at least 8 d. Serum stability experiments demonstrated that at 5 hr 67Ga(tachta) exists in serum as a free complex. At 24 hr, 30% of 67Ga(tachta) is reversibly bound to transferrin-albumin fraction of serum, and that this percentage remains unchanged for a period of 4 d. Biodistribution in mice showed that 67Ga(tachta) rapidly clears via the kidneys from the body with less than 10% of injected activity left in the body at 3 hours and only 6% remaining after 24 hr. The complex also cleared rapidly from all of the major organs, with bone showing some slightly increased (1.15% ID/g) 24 hr accumulation, in comparison with the 3 hr time point. Based upon these data, 67Ga(tachta) may be considered as a candidate for developing new Ga(III) radiopharmaceuticals for PET.

Original languageEnglish (US)
Pages (from-to)695-701
Number of pages7
JournalNuclear Medicine and Biology
Volume28
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Acids
Radiopharmaceuticals
Serum
Cyclohexane
In Vitro Techniques
Transferrin
Serum Albumin
Ligands
Kidney
Bone and Bones

Keywords

  • Ga
  • Cis,cis-1,3,5-triaminocyclohexane-N,N′, N″-triacetic acid (tachta)

ASJC Scopus subject areas

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

Cite this

In vitro and in vivo characterization of 67Ga3+ complexes with cis,cis-1,3,5-triamino-cyclohexane-N,N′,N″-triacetic acid derivatives. / Dadachova, E.; Park, C.; Eberly, N.; Ma, D.; Paik, C. H.; Brechbiel, M. W.

In: Nuclear Medicine and Biology, Vol. 28, No. 6, 2001, p. 695-701.

Research output: Contribution to journalArticle

Dadachova, E. ; Park, C. ; Eberly, N. ; Ma, D. ; Paik, C. H. ; Brechbiel, M. W. / In vitro and in vivo characterization of 67Ga3+ complexes with cis,cis-1,3,5-triamino-cyclohexane-N,N′,N″-triacetic acid derivatives. In: Nuclear Medicine and Biology. 2001 ; Vol. 28, No. 6. pp. 695-701.
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abstract = "The aim of this study was to investigate the in vitro and in vivo performance of a 67Ga complex with cis,cis-1,3,5-triaminocyclohexane-N,N′,N″-triacetic acid (tachta) as a potential ligand for use as a Ga(III) radiopharmaceutical for PET imaging. The radiolabeling procedure, electrophoretic properties, lipophilicity, acid stability, human serum stability and biodistribution in mice of 67Ga(tachta) were investigated. The 67Ga(tachta) complex forms at 10-3 M tachta concentration at 40°C in 100{\%} yield; it is neutral, non-lipophilic, 90{\%} stable at pH = 4 and 5 and 100{\%} stable at pH = 6, for at least 8 d. Serum stability experiments demonstrated that at 5 hr 67Ga(tachta) exists in serum as a free complex. At 24 hr, 30{\%} of 67Ga(tachta) is reversibly bound to transferrin-albumin fraction of serum, and that this percentage remains unchanged for a period of 4 d. Biodistribution in mice showed that 67Ga(tachta) rapidly clears via the kidneys from the body with less than 10{\%} of injected activity left in the body at 3 hours and only 6{\%} remaining after 24 hr. The complex also cleared rapidly from all of the major organs, with bone showing some slightly increased (1.15{\%} ID/g) 24 hr accumulation, in comparison with the 3 hr time point. Based upon these data, 67Ga(tachta) may be considered as a candidate for developing new Ga(III) radiopharmaceuticals for PET.",
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AU - Dadachova, E.

AU - Park, C.

AU - Eberly, N.

AU - Ma, D.

AU - Paik, C. H.

AU - Brechbiel, M. W.

PY - 2001

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N2 - The aim of this study was to investigate the in vitro and in vivo performance of a 67Ga complex with cis,cis-1,3,5-triaminocyclohexane-N,N′,N″-triacetic acid (tachta) as a potential ligand for use as a Ga(III) radiopharmaceutical for PET imaging. The radiolabeling procedure, electrophoretic properties, lipophilicity, acid stability, human serum stability and biodistribution in mice of 67Ga(tachta) were investigated. The 67Ga(tachta) complex forms at 10-3 M tachta concentration at 40°C in 100% yield; it is neutral, non-lipophilic, 90% stable at pH = 4 and 5 and 100% stable at pH = 6, for at least 8 d. Serum stability experiments demonstrated that at 5 hr 67Ga(tachta) exists in serum as a free complex. At 24 hr, 30% of 67Ga(tachta) is reversibly bound to transferrin-albumin fraction of serum, and that this percentage remains unchanged for a period of 4 d. Biodistribution in mice showed that 67Ga(tachta) rapidly clears via the kidneys from the body with less than 10% of injected activity left in the body at 3 hours and only 6% remaining after 24 hr. The complex also cleared rapidly from all of the major organs, with bone showing some slightly increased (1.15% ID/g) 24 hr accumulation, in comparison with the 3 hr time point. Based upon these data, 67Ga(tachta) may be considered as a candidate for developing new Ga(III) radiopharmaceuticals for PET.

AB - The aim of this study was to investigate the in vitro and in vivo performance of a 67Ga complex with cis,cis-1,3,5-triaminocyclohexane-N,N′,N″-triacetic acid (tachta) as a potential ligand for use as a Ga(III) radiopharmaceutical for PET imaging. The radiolabeling procedure, electrophoretic properties, lipophilicity, acid stability, human serum stability and biodistribution in mice of 67Ga(tachta) were investigated. The 67Ga(tachta) complex forms at 10-3 M tachta concentration at 40°C in 100% yield; it is neutral, non-lipophilic, 90% stable at pH = 4 and 5 and 100% stable at pH = 6, for at least 8 d. Serum stability experiments demonstrated that at 5 hr 67Ga(tachta) exists in serum as a free complex. At 24 hr, 30% of 67Ga(tachta) is reversibly bound to transferrin-albumin fraction of serum, and that this percentage remains unchanged for a period of 4 d. Biodistribution in mice showed that 67Ga(tachta) rapidly clears via the kidneys from the body with less than 10% of injected activity left in the body at 3 hours and only 6% remaining after 24 hr. The complex also cleared rapidly from all of the major organs, with bone showing some slightly increased (1.15% ID/g) 24 hr accumulation, in comparison with the 3 hr time point. Based upon these data, 67Ga(tachta) may be considered as a candidate for developing new Ga(III) radiopharmaceuticals for PET.

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