ICRU REPORT 96, Dosimetry-Guided Radiopharmaceutical Therapy

Radiopharmaceutical therapy (RPT) is a radiation delivery modality that uses radionuclides to irradiate tissues with various forms of ionizing radiation. In most forms of RPT, the radionuclide is targeted to the diseased tissue following systemic administration of the pharmaceutical that circulates throughout the body and delivers radiation to sites of radiopharmaceutical accumulation. Three major classes of radionuclides are used in RPT including beta-particle emitters, alpha-particle emitters, and Auger-electron emitters. Recent therapeutic successes and regulatory approval of some commercial radiopharmaceuticals have spurred development of new agents. Unfortunately, comparisons of clinical results and optimization of RPT are hindered by the absence of standardized practices for prescribing, reporting, and recording of dosimetric quantities related to RPT. The present report provides information necessary to standardize techniques and procedures and to harmonize the clinical prescription, recording, and reporting of dosimetry for RPT in a manner that facilitates the use of RPT alone or in combination with other modalities. The Report's introduction briefly outlines the rationale and historical development of RPT. Then fundamental concepts of radionuclides and radiation dosimetry are reviewed. This is followed by a description of the radiobiology of RPT as compared with external photon radiation, along with bioeffect models used to calculate relative biological effectiveness (RBE) and equieffective dose for treatment planning. The cornerstone of the report comprises key concepts and terminology needed to implement dosimetry and treatment planning for RPT. These definitions are used in the recommended absorbed dose prescriptions. Essential to this end are reproducible procedures for quantifying activity in the various source regions. Accordingly, an extensive set of recommendations for activity quantification are described within, along with how to acquire and use pharmacokinetic data to obtain the time integrated activity in source regions. This is followed by methods to calculate the absorbed dose to the dosimetric treatment regions and regions at risk (RARs). The implementation of absorbed dose in RPT treatment planning, and in combination therapies, is then addressed. Subsequent sections describe recommendations for prescribing, recording, and reporting treatments. The report ends with four clinical examples of RPT for different tumor entities to illustrate the application of the recommendations. Specific recommendations in this report include the use of the quantity equieffective dose (EQDX) in units of gray (Gy) which accounts for the dependence of radiobiological responses on absorbed dose rate, fractionation, and linear energy transfer (LET). To avoid confusion, both absorbed dose and equieffective dose should be specified. A new quantity, the standardized relative biological effectiveness (sRBEX), is defined to facilitate bioeffect modeling for high LET radiations such as alpha particles and Auger electrons. In addition, new ICRU definitions of regions and geometric concepts to be used in RPT include localization regions, source regions, clinical treatment regions, dosimetric treatment regions, and RARs; reflecting a unique aspect of RPT relative to radiotherapy, these regions may be delineable or nondelineable. Finally, analogous to external beam radiation therapy, specific recommendations for ICRU reporting levels for RPT are recommended which are specific to each radiopharmaceutical. The Report should be an important and useful reference for all practitioners in RPT and should facilitate comparisons of clinical results from different centers. The focus of dosimetry-guided RPT makes explicit the potential of RPT to target and control tumors while reducing normal tissue toxicity. For all new users and interested readers, the description of the basic concepts and background of RPT should enable them to understand the techniques involved in RPT.