Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with ¹³¹I-CLR1404

• Main Authors: Sara Neira (Author), Araceli Gago-Arias (Author), Isabel Gónzalez-Crespo (Author), Jacobo Guiu-Souto (Author), Juan Pardo-Montero (Author)
• Format: Book
• Published: MDPI AG, 2021-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics13091497; 1999-4923
• Keywords: biokinetics; compartmental model; iodine; molecular radiotherapy; CLR1404; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 13, Iss 9, p 1497 (2021)

Pharmacokinetic modeling of the radiopharmaceuticals used in molecular radiotherapy is an important step towards accurate radiation dosimetry of such therapies. In this paper, we present a pharmacokinetic model for CLR1404, a phospholipid ether analog that, labeled with ¹²⁴I/¹³¹I, has emerged as a promising theranostic agent. We follow a systematic approach for the model construction based on a decoupling process applied to previously published experimental data, and using the goodness-of-fit, Sobol's sensitivity analysis, and the Akaike Information Criterion to construct the optimal form of the model, investigate potential simplifications, and study factor prioritization. This methodology was applied to previously published experimental human time-activity curves for 9 organs. The resulting model consists of 17 compartments involved in the CLR1404 metabolism. Activity dynamics in most tissues are well described by a blood contribution plus a two-compartment system, describing <i>fast</i> and <i>slow</i> uptakes. The model can fit both clinical and pre-clinical kinetic data of ¹²⁴I/¹³¹I. In addition, we have investigated how simple fits (exponential and biexponential) differ from the complete model. Such fits, despite providing a less accurate description of time-activity curves, may be a viable alternative when limited data is available in a practical case.