Characterisation of 67Ga3+ complexes of triaza macrocyclic ligands: biodistribution and clearance studies.
The 67Ga3+ complexes of three triazamacrocycles, 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA), its phosphonate analog 1,4,7-triazacyclononane-N,N',N''-tris(methylenephosphonic) acid (NOTP), and the monoethyl ester of NOTP, 1,4,7-triazacyclononane-N,N',N''-tris (methylenephosphonate-monoethylester) (NOTPME) were studied for possible use as radiopharmaceuticals. Biodistribution studies and gamma imaging were performed in Wistar rats. The present results demonstrated that all the macrocyclic complexes studied display renal clearance and are almost completely eliminated within 24 h. The [67Ga](NOTP)3- chelate, with a large negative charge, has a considerably slower uptake and elimination by the kidneys than the neutral [67Ga](NOTA) and [67Ga](NOTPME) chelates. We have thus demonstrated a charge-clearance relationship for a series of stable and well characterized complexes. The high stability and rapid renal excretion properties displayed by the NOTA and NOTPME chelates support their possible application as imaging agents for kidney structural and functional studies.
Prata
M I
MI
Serviço de Biofísica e Biomatemática, Fac. Medicina, Universidade de Coimbra, Portugal.
Santos
A C
AC
Geraldes
C F
CF
de Lima
J J
JJ
D000818:Animals; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics*; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D006573:Heterocyclic Compounds, 1-Ring; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008657:Metabolic Clearance Rate; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution
D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C402168:gallium 1,4,7-triazacyclononane-N,N',N''-tris(methylenephosphonic acid); C068116:1,4,7-triazacyclononane-N,N',N''-tris(methylenephosphonate monoethyl ester); C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid