Cationic technetium-99m complexes of N-substituted pyridoxal derivatives as renal function agents

New cationic technetium-chelating agents containing a pyridinium group have been synthesized and evaluated as potential renal radiopharmaceuticals.

The pyridinium compounds used in the study are N-methyl pyridoxal chloride, N-ethyl pyridoxal chloride, N-propyl pyridoxal chloride, 1-methyl-3-hydroxy-4-formylpyridinium chloride, 1-methyl-2-formyl-3-hydroxypyridinium chloride and the Schiff's bases of N-methyl pyridoxal chloride with amino acid, amino acid ester and amino acid amide. Complexes of these chelating agents with 99mTc were prepared using a Na2S2O4 or a SnCl2 solution as a reducing agent. The purity of the 99mTc complexes was determined by paper electrophoresis in 0.1 M tris buffer.

Electrophoresis indicates slightly positive-charged species. The log P values of these complexes showed a hydrophilic nature. Urinary excretion of the 99mTc N-alkylated pyridoxal derivatives, 99mTc-diethylenetriaminepentaacetic acid, 99mTc-mercaptoacetylglycylglycylglycine (MAG3) and 131I-O-iodohippurate were determined in mice and rats at different time intervals. In a rat model, the pyridoxal-derived 99mTc complexes are rapidly excreted in urine and provide clear renal scintigrams. Hepatobiliary excretion was negligible, reducing scan interference from the intestines. Total clearances were lower than that of 131I-hippurate and 99mTc-MAG3.

The rate of urinary clearance of the new tracers was not significantly faster than 99mTc diethylenetriaminepentaacetic acid and the inhibitor N1-methylnicotinamide had only a minimal effect on the renal behavior. Though the new tracers have cationic properties, the pyridinium group did not contribute largely to the excretion of active transport.