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

EJNMMI Radiopharmacy and Chemistry
Tilman LäppchenMark D Bartholomä

Abstract

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. 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 spe...Continue Reading

References

Dec 15, 1992·European Journal of Biochemistry·M GurrathR Timpl
Mar 15, 2003·Nature Reviews. Cancer·John D Hood, David A Cheresh
Jan 22, 2004·Bioconjugate Chemistry·Roland HaubnerMarkus Schwaiger
Jun 19, 2007·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Zi-Bo LiXiaoyuan Chen
Mar 29, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Clemens DecristoforoRoland Haubner
Jul 1, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Pat Zanzonico
Jun 13, 2009·Current Cancer Drug Targets·H M Sheldrake, L H Patterson
Sep 22, 2010·European Journal of Nuclear Medicine and Molecular Imaging·Ingrid DijkgraafOtto C Boerman
Jul 19, 2011·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Rebecca A DumontMelpomeni Fani
Mar 3, 2012·Nuclear Medicine and Biology·Eszter BorosChris Orvig
Sep 22, 2012·Nuclear Medicine and Biology·Johannes NotniHans-Jürgen Wester
Oct 6, 2012·Bioconjugate Chemistry·Cara L FerreiraGarry E Kiefer
Nov 29, 2013·Journal of Labelled Compounds & Radiopharmaceuticals·Hancheng Cai, Peter S Conti
Feb 27, 2015·Bioconjugate Chemistry·Jason L J DearlingAlan B Packard
Sep 30, 2016·Current Cardiovascular Imaging Reports·Ljubica MandicMariann Gyöngyösi
Mar 16, 2017·Journal of Leukocyte Biology·Ioannis KourtzelisTriantafyllos Chavakis

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Citations

Aug 29, 2020·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Sebastian MartinMark D Bartholomä
Oct 3, 2018·Organic & Biomolecular Chemistry·Christian WeinmannMark D Bartholomä
May 30, 2021·Current Opinion in Chemical Biology·Deborah Sneddon, Bart Cornelissen

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Methods Mentioned

BETA
xenografts

Software Mentioned

GraphPad Prism
NODIA

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