Study On The Complexation Of [^99mTc(CO)₃]⁺-DOTMP

Multidentate aminomethylenephosphonic acids form stable complexes with differentradionuclides and have already been proven to be very effective for diagonose and therapyof bone metastases.A cyclic polyaminomethylenephosphonic acid DOTMP(1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetra(methylenephosphonic acid)) was synthesized, the radiolabeling of[^99mTc(CO)₃]⁺-DOTMP using the precursor of [^99mTc(CO)₃]⁺ and in vitro and in vivoevaluation of this conjugate were studied. Complexation of [^99mTc(CO)₃]⁺-DOTMP wascarried out by varying experimental parameters such as ligand concentration, pH, time andtemperature of reaction to obtain quantitative yields, and its in vitro stability wasinvestigated in detail. The biodistribution of the compound [^99mTc(CO)₃]⁺-DOTMP werestudied in normal mice and the scintigraphic studies were carried out in the normal rabbitcompared with the traditional bone-seeking agent ^99mTc-MDP.Under optimum conditions, the radiolabeled yield of [^99mTc(CO)₃]⁺-DOTMP was inexcess of 90%. The in vitro stability of [^99mTc(CO)₃]⁺-DOTMP was good. Biodistributionstudies of the compound in normal mice demonstrated prominent bone localization,retention, a low uptake in soft tissues and excretion mainly through the renal/urinarysystem. Among the soft tissue organs, liver and blood had a relatively high uptake. Noleaching of skeletal activity was observed up to 3h post-injection. In a rabbit, thescintigraphic images obtained with the new agent showed good quality bone scans, withclear visualization of the skeleton and low soft tissue activity at respectively 2 to 3h afterinjection.In conclusion, the radiolabeled tetraphosphonate [^99mTc(CO)₃]⁺-DOTMP may be apotential bone-seeking compound.