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

Phosphonic acids labeled with rhenium-188 ( 188 Re) are promising bone-seeking radiopharmaceuticals (RPs) for bone metastases therapy. The present work was aimed to develop a compartmental mathematical model of 188 Re-pentaphosphonic acid ( 188 Re-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 188 Re-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.