Calculation of pharmacokinetic and dosimetric characteristics of Lu-177-EDTMP – a potential drug for radionuclide therapy of bone metastases

Phosphonic acids labeled with beta-emitting radionuclides are promising radiopharmaceutical drugs for palliative therapy of bone metastases. Currently, the possibility of using a new osteotropic compound N,N,N’,N’-ethylenediaminetetrakis (methylene phosphonic acid) with lutetium-177 (177Lu-EDTMP) is being studied. The aim of the work is to develop a compartment mathematical model of the kinetics of 177Lu labeled osteotropic radiopharmaceutical drugs in the body of laboratory animals and calculate their pharmacokinetic and dosimetric characteristics based on it. To assess the stability of 177Lu-EDTMP in vivo, the characteristics of the distribution of free lutetium in the form of 177LuCl3 were also studied. To identify the model parameters and calculate the characteristics of radiopharmaceutical drugs, quantitative data on the bio-distribution of 177Lu-EDTMP and 177LuCl3 in the body of intact Wistar rats were used. A compartment model of kinetics has been developed and two approaches to the identification of its transport constants have been proposed – through the residual functional and using approximation by monoexponential functions. According to pharmacokinetic modeling, it was found that 177Lu-EDTMP is deposited in bone tissues (up to 55% of the administered dose). The calculated value of the apparent volume of distribution of 177Lu-EDTMP is approximately 200 times greater than the volume of blood plasma, the values of biological half-lives from bone tissues are 10-20 times higher than from internal organs. The excretion of 177Lu-EDTMP from the body occurs mainly through renal clearance. Comparative modeling with 177LuCl3 revealed high resistance of 177Lu-EDTMP in vivo. The highest values of absorbed doses are formed in the skeleton and kidneys with minimal radiation load on other internal organs and blood. The results obtained indicate the prospects for further studies of 177Lu-EDTMP and the possibility of its clinical application for the treatment of skeletal metastases.