Preparation and characterization of technetium and rhenium tricarbonyl complexes bearing the 4-nitrobenzyl moiety as potential bioreductive diagnostic radiopharmaceuticals. In vitro and in vivo studies.
The synthesis of a ligand containing a nitrobenzyl group as bioreductive pharmacophore and the preparation of the corresponding technetium and rhenium complexes are presented. (99m)Tc labelling was performed in high yield (>90%) by ligand substitution using fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) as precursor. The structure of the technetium complex was established by chromatographic comparison with the analogous rhenium compound which was fully characterized by elemental analysis, spectroscopic methods and X-ray crystallography. Reduction potential of the rhenium complex was in the characteristic range for bioreductive compounds. Biodistribution in normal mice was characterized by fast blood and soft tissue depuration and combined excretion via the hepatobiliary and urinary systems. Tumour uptake was low, probably due to low lipophilicity but tumour/muscle ratios were favourable as a consequence of high excretion.
Cátedra de Radioquímica, Facultad de Química, General Flores 2124, Montevideo 11800, Uruguay.
Javier
J
Giglio
Georgios
G
Patsis
Ioannis
I
Pirmettis
Minas
M
Papadopoulos
Catherine
C
Raptopoulou
Maria
M
Pelecanou
Elsa
E
León
Mercedes
M
González
Hugo
H
Cerecetto
Ana
A
Rey
D000818:Animals; D015687:Cell Hypoxia; D018360:Crystallography, X-Ray; D003952:Diagnostic Imaging; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012211:Rhenium / Q000737:chemistry*; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012211:Rhenium