A gallium complex with a new tripodal tris-hydroxypyridinone for potential nuclear diagnostic imaging: solution and in vivo studies of 67Ga-labeled species.
The gallium(III) complex of a new tripodal 3-hydroxy-4-pyridinone (3,4-HP) chelator has been studied in terms of its physico-chemical and in vivo properties aimed at potential application as probe for nuclear imaging. In particular, based on spectrophotometric titrations, the hexa-coordinated (1:1) gallium complex appeared as the major species in a wide physiological acid-neutral pH range and its high stability (pGa=27.5) should avoid drug-induced toxicity resulting from Ga(III) accumulation in tissues due to processes of transmetallation with endogenenous ligands or demetallation. A multinuclear ((1)H and (71)Ga) NMR study gave some insights into the structure and dynamics of the gallium(III) chelate in solution, which are consistent with the tris-(3,4-HP) coordination and an eventual pseudo-octahedral geometry. Biodistribution and scintigraphic studies of the (67)Ga(III) labelled chelate, performed in Wistar rats, confirmed the in vivo stability of the radiolabelled complex, its non interaction with blood proteins and its quick renal clearance. These results indicate good perspectives for potential application of extrafunctionalized analogues in radiodiagnostic techniques.
Centro de Química Estrutural, Instituto Superior Técnico-UTL, 1049-001 Lisboa, Portugal.
Sílvia
S
Chaves
Ana C
AC
Mendonça
Sérgio M
SM
Marques
M Isabel
MI
Prata
Ana C
AC
Santos
André F
AF
Martins
Carlos F G C
CF
Geraldes
M Amélia
MA
Santos
D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D005710:Gallium Radioisotopes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009942:Organometallic Compounds / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D011728:Pyridones / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D005710:Gallium Radioisotopes; D009942:Organometallic Compounds; D011725:Pyridines; D011728:Pyridones; C014047:hydroxypyridines