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Compartmental Modeling of the Kinetics of 188Re-Labeled Pentaphosphonic Acid in Rats with Bone Callus

  • MOLECULAR-BIOLOGICAL PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION
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Pharmaceutical Chemistry Journal Aims and scope

Phosphonic acids labeled with rhenium-188 (188Re) are promising bone-seeking radiopharmaceuticals (RPs) for bone metastases therapy. The present work was aimed to develop a compartmental mathematical model of 188Re-pentaphosphonic acid (188Re-PPA) kinetics and calculate its pharmacokinetic transport parameters in healthy experimental animals and animals with bone pathology. The developed compartmental model of drug kinetics proposed two approaches to identify the transport constants that were based on the residual functional and an approximation of monoexponential functions. It was found that the presence of bone callosity significantly affected the biodistribution of 188Re-PPA in organs and tissues. The transport constants of excretion for all bone tissues in rats with a femoral callus were 10 times lower and the biological half-life was 5 times higher than in healthy rats. The highest activities were registered in bones, bone callus, kidneys, and liver. Results of the compartmental modeling and mathematical calculations of the pharmacokinetic parameters confirmed quantitatively significant changes in the biodistribution of the studied RP in rats with bone pathology as compared to healthy rats.

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Authors and Affiliations

  1. F. M. Dostoevsky Omsk State University, 11 Neftezavodskaya St., Omsk, 644053, Russia

    A. V. Matveev

  2. A. F. Tsyb Medical Radiological Research Center, Branch of the National Medical Radiological Research Center, Ministry of Health of the Russian Federation, 4 Koroleva St., Obninsk, Kaluga Oblast, 249036, Russia

    V. M. Petriev & V. K. Tishchenko

  3. National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), 31 Kashirskoe Shosse, Moscow, 115409, Russia

    V. M. Petriev

Authors
  1. A. V. Matveev
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  2. V. M. Petriev
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  3. V. K. Tishchenko
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Correspondence to V. M. Petriev.

Additional information

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 55, No. 11, pp. 3 – 9, November, 2021.

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Matveev, A.V., Petriev, V.M. & Tishchenko, V.K. Compartmental Modeling of the Kinetics of 188Re-Labeled Pentaphosphonic Acid in Rats with Bone Callus. Pharm Chem J 55, 999–1005 (2022). https://doi.org/10.1007/s11094-021-02528-4

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  • DOI: https://doi.org/10.1007/s11094-021-02528-4

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