Jump to main content
Jump to site search

Issue 21, 2014
Previous Article Next Article

Ga[NO2A-N-(α-amino)propionate] chelates: synthesis and evaluation as potential tracers for 68Ga PET

Author affiliations

Abstract

The availability of commercial 68Ge/68Ga cyclotron-independent 68Ga3+ generators is making Positron Emission Tomography (PET) accessible to most hospitals, which is generating a surge of interest in the design and synthesis of bi-functional chelators for Ga3+. In this work we introduce the NO2A-N-(α-amino)propionic acid family of chelators based on the triazacyclononane scaffold. Complexation of the parent NO2A-N-(α-amino)propionic acid chelator and of a low molecular weight (model) amide conjugate with Ga3+ was studied by 1H and 71Ga NMR. The Ga3+ chelate of the amide conjugate shows pH-independent N3O3 coordination in the pH range 3–10 involving the carboxylate group of the pendant propionate arm in a 6 member chelate. For the Ga[NO2A-N-(α-amino)propionate] chelate, a reversible pH-triggered switch from Ga3+ coordination to the carboxylate group to coordination to the amine group of the propionate arm was observed upon pH increase/decrease in the pH range 4–6. This phenomenon can conceivably constitute the basis of a physiological pH sensor. Both complexes are stable in the physiological range. The [67Ga][NO2A-N-(α-benzoylamido)propionate] chelate was found to be stable in human serum. Biodistribution studies of the 67Ga3+-labeled pyrene butyric acid conjugate NO2A-N-(α-pyrenebutanamido)propionic acid revealed that, despite its high lipophilicity and concentration-dependent aggregation properties, the chelate follows mainly renal elimination with very low liver/spleen accumulation and no activity deposition in bones after 24 hours. Facile synthesis of amide conjugates of the NO2A-N-(α-amino)propionic acid chelator, serum stability of the Ga3+ chelates and fast renal elimination warrant further evaluation of this novel class of chelators for PET applications.

Graphical abstract: Ga[NO2A-N-(α-amino)propionate] chelates: synthesis and evaluation as potential tracers for 68Ga PET

Back to tab navigation

Supplementary files

Publication details

The article was received on 06 Feb 2014, accepted on 07 Mar 2014 and first published on 09 Apr 2014


Article type: Paper
DOI: 10.1039/C4DT00386A
Author version available: Download Author version (PDF)
Citation: Dalton Trans., 2014,43, 8037-8047
  •   Request permissions

    Ga[NO2A-N-(α-amino)propionate] chelates: synthesis and evaluation as potential tracers for 68Ga PET

    M. F. Ferreira, G. Pereira, J. P. André, M. I. M. Prata, P. M. T. Ferreira, J. A. Martins and C. F. G. C. Geraldes, Dalton Trans., 2014, 43, 8037
    DOI: 10.1039/C4DT00386A

Search articles by author

Spotlight

Advertisements