99mTc-tetracycline radiopharmaceutical: physical chemistry study related to the preparation and reaction products and thermodynamic stability.

The labelling of tetracycline hydrochloride with 99mTc at neutral pH, using Sn2+ as reducing agent, has been investigated by chromatography, using a 4:1:5 n-butanol:acetic acid:H2O mixture as developing agent, with Whatman paper No 3. In such conditions, reduced 99mTc remained at the origin, while labelled 99mTc migrates at Rf approximately equal to 0.6. Radiochromatographic and u.v.-visible spectrophotometric results, demonstrated that the higher the tetracycline concentration the higher was the labelling of 99mTc to that ligand, obtaining a 50% labelling when the molar ratio of tetracycline:Sn2+ was approximately 20:1, independent of the Tc concentration level. The Tc oxidation state in the radiopharmaceutical is +4, deduced from iodimetric and radiometric techniques. Furthermore, it seems that time does not influence labelling, while pH does. The maximum labelling level occurs at physiological pH. The thermodynamic study performed with the radiopharmaceutical formation shows that the Tc-tetracycline complex has a 1:1 stoichiometry, thus a low stability constant (about 2 X 10(2)).