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

«Radiation and Risk», 2023, vol. 32, No. 2, pp.96-109

DOI: 10.21870/0131-3878-2023-32-2-96-109

Authors

Matveev A.V. – Associate Prof., C. Sc., Phys.-Math. Dostoevsky OmSU. Contacts: 55A Mira av., Omsk, Russia, 644077. Tel.: +79043251774; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Petriev V.M. – Head of Lab., D. Sc., Biol., Prof. of MEPhI
Tishchenko V.K. – Lead. Researcher, D. Sc., Biol.
Minaeva N.G. – Sen. Researcher, C. Sc., Biol. A. Tsyb MRRC.
¹ Dostoevsky Omsk State University, Omsk
² A. Tsyb MRRC, Obninsk
³ National Research Nuclear University MEPhI, Moscow

Abstract

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.

Key words
pharmacokinetics, dosimetry, lutetium-177, radiopharmaceutical, EDTMP, modeling, nuclear medicine, radionuclide therapy, absorbed doses, bone metastases.

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