Comparison of different phosphorus-containing ligands complexing 68Ga for PET-imaging of bone metabolism

M. Fellner, P. Riss, N. Loktionova, K. Zhernosekov, O. Thews, C. F G C Geraldes, Z. Kovacs, I. Lukeš, F. Rösch

Research output: Contribution to journalArticle

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Abstract

99mTc-phosphonate structures are well established tracers for bone tumour imaging. Our objective was to investigate different 68Ga-labelled phosphonate ligands concerning labelling kinetics, binding to hydroxyapatite and bone imaging using μ-PET. Seven macrocyclic phosphoruscontaining ligands and EDTMP were labelled in nanomolar scale with n.c.a. 68Ga in Na-HEPES buffer at pH ∼ 4. Except for DOTP, all ligands were labelled with > 92% yield. Binding of the 68Ga-ligand complexes on hydroxyapatite was analysed to evaluate the effect of the number of the phosphorus acid groups on adsorption parameters. Adsorption of 68Ga-EDTMP and 68Ga-DOTP was > 83%. For the 68Ga-NOTA-phosphonates an increasing binding with increasing number of phosphonate groups was observed but was still lower than 68Ga-DOTP and 68Ga-EDTMP. μ-PET studies in vivo were performed with 68Ga-EDTMP and 68Ga-DOTP with Wistar rats. While 68Ga-EDTMP-PET showed uptake on bone structures, an excess amount of the ligand (> 1.5 mg EDTMP/kg body weight) had to be used, otherwise the 68Ga3+ is released from the complex and forms gallium hydroxide or it is transchelated to 68Ga-transferrin. As a result, the main focus of further phosphonate structures has to be on complex formation in high radiochemical yields with macrocyclic ligands with phosphonate groups that are not required for complexing 68Ga.

Original languageEnglish (US)
Pages (from-to)43-51
Number of pages9
JournalRadiochimica Acta
Volume99
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

(ethylenedinitrilo)-tetramethylenephosphonic acid
Organophosphonates
metabolism
Metabolism
Phosphorus
bones
phosphorus
Bone
Ligands
Imaging techniques
ligands
Durapatite
Phosphorus Acids
HEPES
Adsorption
body weight
Gallium
adsorption
Transferrin
Labeling

Keywords

  • Bone metastases
  • Complex formation
  • Ga-68
  • Macrocylic ligands
  • Phosphonates

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry

Cite this

Fellner, M., Riss, P., Loktionova, N., Zhernosekov, K., Thews, O., Geraldes, C. F. G. C., ... Rösch, F. (2011). Comparison of different phosphorus-containing ligands complexing 68Ga for PET-imaging of bone metabolism. Radiochimica Acta, 99(1), 43-51. https://doi.org/10.1524/ract.2011.1791

Comparison of different phosphorus-containing ligands complexing 68Ga for PET-imaging of bone metabolism. / Fellner, M.; Riss, P.; Loktionova, N.; Zhernosekov, K.; Thews, O.; Geraldes, C. F G C; Kovacs, Z.; Lukeš, I.; Rösch, F.

In: Radiochimica Acta, Vol. 99, No. 1, 01.2011, p. 43-51.

Research output: Contribution to journalArticle

Fellner, M, Riss, P, Loktionova, N, Zhernosekov, K, Thews, O, Geraldes, CFGC, Kovacs, Z, Lukeš, I & Rösch, F 2011, 'Comparison of different phosphorus-containing ligands complexing 68Ga for PET-imaging of bone metabolism', Radiochimica Acta, vol. 99, no. 1, pp. 43-51. https://doi.org/10.1524/ract.2011.1791
Fellner, M. ; Riss, P. ; Loktionova, N. ; Zhernosekov, K. ; Thews, O. ; Geraldes, C. F G C ; Kovacs, Z. ; Lukeš, I. ; Rösch, F. / Comparison of different phosphorus-containing ligands complexing 68Ga for PET-imaging of bone metabolism. In: Radiochimica Acta. 2011 ; Vol. 99, No. 1. pp. 43-51.
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N2 - 99mTc-phosphonate structures are well established tracers for bone tumour imaging. Our objective was to investigate different 68Ga-labelled phosphonate ligands concerning labelling kinetics, binding to hydroxyapatite and bone imaging using μ-PET. Seven macrocyclic phosphoruscontaining ligands and EDTMP were labelled in nanomolar scale with n.c.a. 68Ga in Na-HEPES buffer at pH ∼ 4. Except for DOTP, all ligands were labelled with > 92% yield. Binding of the 68Ga-ligand complexes on hydroxyapatite was analysed to evaluate the effect of the number of the phosphorus acid groups on adsorption parameters. Adsorption of 68Ga-EDTMP and 68Ga-DOTP was > 83%. For the 68Ga-NOTA-phosphonates an increasing binding with increasing number of phosphonate groups was observed but was still lower than 68Ga-DOTP and 68Ga-EDTMP. μ-PET studies in vivo were performed with 68Ga-EDTMP and 68Ga-DOTP with Wistar rats. While 68Ga-EDTMP-PET showed uptake on bone structures, an excess amount of the ligand (> 1.5 mg EDTMP/kg body weight) had to be used, otherwise the 68Ga3+ is released from the complex and forms gallium hydroxide or it is transchelated to 68Ga-transferrin. As a result, the main focus of further phosphonate structures has to be on complex formation in high radiochemical yields with macrocyclic ligands with phosphonate groups that are not required for complexing 68Ga.

AB - 99mTc-phosphonate structures are well established tracers for bone tumour imaging. Our objective was to investigate different 68Ga-labelled phosphonate ligands concerning labelling kinetics, binding to hydroxyapatite and bone imaging using μ-PET. Seven macrocyclic phosphoruscontaining ligands and EDTMP were labelled in nanomolar scale with n.c.a. 68Ga in Na-HEPES buffer at pH ∼ 4. Except for DOTP, all ligands were labelled with > 92% yield. Binding of the 68Ga-ligand complexes on hydroxyapatite was analysed to evaluate the effect of the number of the phosphorus acid groups on adsorption parameters. Adsorption of 68Ga-EDTMP and 68Ga-DOTP was > 83%. For the 68Ga-NOTA-phosphonates an increasing binding with increasing number of phosphonate groups was observed but was still lower than 68Ga-DOTP and 68Ga-EDTMP. μ-PET studies in vivo were performed with 68Ga-EDTMP and 68Ga-DOTP with Wistar rats. While 68Ga-EDTMP-PET showed uptake on bone structures, an excess amount of the ligand (> 1.5 mg EDTMP/kg body weight) had to be used, otherwise the 68Ga3+ is released from the complex and forms gallium hydroxide or it is transchelated to 68Ga-transferrin. As a result, the main focus of further phosphonate structures has to be on complex formation in high radiochemical yields with macrocyclic ligands with phosphonate groups that are not required for complexing 68Ga.

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