Synthesis and characterization of thiol containing furoxan derivatives as coligands for the preparation of potential bioreductive radiopharmaceuticals.
The synthesis and characterization of thiol-containing 1,2,5-oxadiazole N-oxide (TONO) derivatives and their use as monodentate coligands for the preparation of (99m)Tc complexes is presented. 3-Mercaptomethyl-4-phenyl-1,2,5-oxadiazol N(2)-oxide and 3-(4-mercaptophenylmethylidenhydrazinocarbonyloxymethyl)-4-phenyl-1,2,5-oxadiazol N(2)-oxide were successfully synthesized and combined with the tridentate ligand N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA) to prepare "3+1 mixed ligand" technetium complexes. The( 99m)Tc complexes were obtained in high yield and radiochemical purity using low concentration of ligand and coligand. An alternative procedure using a xantate and a disulphide precursor of 3-mercaptomethyl-4-phenyl-1,2,5-oxadiazol N(2)-oxide yielded the same complex. Biological evaluation of the potentiality of the( 99m)Tc complexes as bioreductive radiopharmaceuticals was performed in normal CD1 mice and in mice bearing induced sarcoma. Tumour uptake was moderate but tumour/soft tissue ratio was favourable. Although these results are encouraging, further development is still necessary in order to achieve higher tumour uptake and lower gastrointestinal activity.
Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. hcerecet@fq.edu.uy
Hugo
H
Cerecetto
Mercedes
M
González
Silvia
S
Onetto
Mariela
M
Risso
Ana
A
Rey
Javier
J
Giglio
Elsa
E
León
Alba
A
León
Pierina
P
Pilatti
Marcelo
M
Fernández
D000818:Animals; D005260:Female; D008024:Ligands; D051379:Mice; D010069:Oxadiazoles / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis*; D013667:Technetium; D014018:Tissue Distribution
D008024:Ligands; D010069:Oxadiazoles; D019275:Radiopharmaceuticals; D013438:Sulfhydryl Compounds; C010166:furoxans; D013667:Technetium