Dosimetry for radiopharmaceutical therapy

Abstract

Radiopharmaceutical therapy (RPT) involves the use of radionuclides that are either conjugated to tumor-targeting agents (e.g., nanoscale constructs, antibodies, peptides, and small molecules) or concentrated in tissue through natural physiological mechanisms that occur predominantly in neoplastic or otherwise targeted cells (e.g., Graves disease). The ability to collect pharmacokinetic data by imaging and use this to perform dosimetry calculations for treatment planning distinguishes RPT from other systemic treatment modalities such as chemotherapy, wherein imaging is not generally used. Treatment planning has not been widely adopted, in part, because early attempts to relate dosimetry to outcome were not successful. This was partially because a dosimetry methodology appropriate to risk evaluation rather than efficacy and toxicity was being applied to RPT. The weakest links in both diagnostic and therapeutic dosimetry are the accuracy of the input and the reliability of the radiobiological models used to convert dosimetric data to the relevant biologic end points. Dosimetry for RPT places a greater demand on both of these weak links. To date, most dosimetric studies have been retrospective, with a focus on tumor dose-response correlations rather than prospective treatment planning. In this regard, transarterial radioembolization also known as intra-arterial radiation therapy, which uses radiolabeled ((90)Y) microspheres of glass or resin to treat lesions in the liver holds much promise for more widespread dosimetric treatment planning. The recent interest in RPT with alpha-particle emitters has highlighted the need to adopt a dosimetry methodology that specifically accounts for the unique aspects of alpha particles. The short range of alpha-particle emitters means that in cases in which the distribution of activity is localized to specific functional components or cell types of an organ, the absorbed dose will be equally localized and dosimetric calculations on the scale of organs or even voxels (~5mm) are no longer sufficient. This limitation may be overcome by using preclinical models to implement macromodeling to micromodeling. In contrast to chemotherapy, RPT offers the possibility of evaluating radiopharmaceutical distributions, calculating tumor and normal tissue absorbed doses, and devising a treatment plan that is optimal for a specific patient or specific group of patients.