Details

Autor(en) / Beteiligte

• Ferreira, Miguel F
• Pereira, Goretti
• André, João P
• Prata, M. I. M
• Ferreira, Paula M. T
• Martins, José A
• Geraldes, Carlos F. G. C

Titel

Ga[NO2A-N-(α-amino)propionate] chelates: synthesis and evaluation as potential tracers for 68Ga PETElectronic supplementary information (ESI) available: 1D proton and 2D COSY NMR spectrum (600 MHz) of GaL1 at pH 3.0 (Fig. S1); 1D proton and 2D COSY NMR spectrum (600 MHz) of GaL1 at pH 4.0 (Fig. S2); UV-Vis spectra for the free ligand L3 and the GaL3 complex (1.0 × 10−5 M) (Fig. S3); Fluorescence spectra for L3 in non-deoxygenated water over the concentration range 1.0 × 10−7 and 5 × 10−3 mol dm−

Erscheinungsjahr

2014-05

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The availability of commercial 68 Ge/ 68 Ga cyclotron-independent 68 Ga 3+ 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 Ga 3+ . 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 Ga 3+ was studied by 1 H and 71 Ga NMR. The Ga 3+ chelate of the amide conjugate shows pH-independent N 3 O 3 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 Ga 3+ 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 [ 67 Ga][NO2A- N -(α-benzoylamido)propionate] chelate was found to be stable in human serum. Biodistribution studies of the 67 Ga 3+ -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 Ga 3+ chelates and fast renal elimination warrant further evaluation of this novel class of chelators for PET applications. A reversible pH-trigged N 3 O 3 N 4 O 2 coordination isomerism was demonstrated for the Ga[NO2A- N -(α-amino)propionate] chelate in the pH range 4-6.