4-N-Alkanoyl and 4-N-alkyl gemcitabine analogues with NOTA chelators for 68-gallium labelling

Jesse Pulido, Maria de Cabrera, Adam J. Sobczak, Alejandro Amor-Coarasa, Anthony J. McGoron, Stanislaw F. Wnuk

Research output: Contribution to journalArticle

Abstract

The conjugation of 4-N-(3-aminopropanyl)-2′-deoxy-2′,2′-difluorocytidine with 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bn-NOTA) ligand in 0.1 M Na2CO3 buffer (pH 11) at ambient temperature provided 4-N-alkylgemcitabine-NOTA chelator. Incubation of latter with excess of gallium(III) chloride (GaCl3) (0.6 N AcONa/H2O, pH = 9.3) over 15 min gave gallium 4-N-alkylgemcitabine-NOTA complex which was characterized by HRMS. Analogous [68Ga]-complexation of 4-N-alkylgemcitabine-NOTA conjugate proceeded with high labeling efficiency (94%–96%) with the radioligand almost exclusively found in the aqueous layer (∼95%). The high polarity of the gallium 4-N-alkylgemctiabine-NOTA complex resulted in rapid renal clearance of the 68Ga-labelled radioligand in BALB/c mice.

Original languageEnglish (US)
Pages (from-to)5624-5630
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume26
Issue number21
DOIs
StatePublished - Nov 15 2018
Externally publishedYes

Fingerprint

gemcitabine
Gallium
Chelating Agents
Labeling
Complexation
Chlorides
Buffers
1,4,7-triazacyclononane-N,N',N''-triacetic acid
Ligands
Kidney
Temperature
Acids

Keywords

  • 68-Gallium
  • Gemcitabine
  • NOTA
  • Nucleosides
  • PET imaging
  • Prodrugs

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

4-N-Alkanoyl and 4-N-alkyl gemcitabine analogues with NOTA chelators for 68-gallium labelling. / Pulido, Jesse; de Cabrera, Maria; Sobczak, Adam J.; Amor-Coarasa, Alejandro; McGoron, Anthony J.; Wnuk, Stanislaw F.

In: Bioorganic and Medicinal Chemistry, Vol. 26, No. 21, 15.11.2018, p. 5624-5630.

Research output: Contribution to journalArticle

Pulido, Jesse ; de Cabrera, Maria ; Sobczak, Adam J. ; Amor-Coarasa, Alejandro ; McGoron, Anthony J. ; Wnuk, Stanislaw F. / 4-N-Alkanoyl and 4-N-alkyl gemcitabine analogues with NOTA chelators for 68-gallium labelling. In: Bioorganic and Medicinal Chemistry. 2018 ; Vol. 26, No. 21. pp. 5624-5630.
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