Preparation and preclinical evaluation of a 68Ga-labelled c(RGDfK) conjugate comprising the bifunctional chelator NODIA-Me View Full Text


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Article Info

DATE

2018-12

AUTHORS

Tilman Läppchen, Jason P. Holland, Yvonne Kiefer, Mark D. Bartholomä

ABSTRACT

Background: We recently developed a chelating platform based on the macrocycle 1,4,7-triazacyclononane with up to three, five-membered azaheterocyclic arms for the development of 68Ga- and 64Cu-based radiopharmaceuticals. Here, a 68Ga-labelled conjugate comprising the bifunctional chelator NODIA-Me in combination with the αvß3-targeting peptide c(RGDfK) has been synthesized and characterized. The primary aim was to evaluate further the potential of our NODIA-Me chelating system for the development of 68Ga-labelled radiotracers. Results: The BFC NODIA-Me was conjugated to c(RGDfK) by standard peptide chemistry to obtain the final bioconjugate NODIA-Me-c(RGDfK) 3 in 72% yield. Labelling with [68Ga]GaCl3 was accomplished in a fully automated, cGMP compliant process to give [68Ga]3 in high radiochemical yield (98%) and moderate specific activity (~ 8 MBq nmol- 1). Incorporation of the Ga-NODIA-Me chelate to c(RGDfK) 2 had only minimal influence on the affinity to integrin αvß3 (IC50 values [natGa]3 = 205.1 ± 1.4 nM, c(RGDfK) 2 = 159.5 ± 1.3 nM) as determined in competitive cell binding experiments in U-87 MG cell line. In small-animal PET imaging and ex vivo biodistribution studies, the radiotracer [68Ga]3 showed low uptake in non-target organs and specific tumor uptake in U-87 MG tumors. Conclusion: The results suggest that the bifunctional chelator NODIA-Me is an interesting alternative to existing ligands for the development of 68Ga-labelled radiopharmaceuticals. More... »

PAGES

6

References to SciGraph publications

  • 2002-02. Role of integrins in cell invasion and migration in NATURE REVIEWS CANCER
  • 2008-08. 68Ga- and 111In-labelled DOTA-RGD peptides for imaging of αvβ3 integrin expression in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 2011-01. PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides in EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
  • 2016-10. Molecular Imaging of Angiogenesis in Cardiac Regeneration in CURRENT CARDIOVASCULAR IMAGING REPORTS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s41181-018-0043-2

    DOI

    http://dx.doi.org/10.1186/s41181-018-0043-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1103763195

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29756024


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