The USFDA approval of the ? particle emitting radiopharmaceutical (RP) radium 223 dichloride (Xofigo) and the ?-particle emitting lutetium 177 dotatate (LUTATHERA), and their successful implementation in the clinic, has contributed to reinvigorated interest in radiopharmaceutical therapy (RPT) of cancer. RPT entails the delivery of radioactive drugs to the primary tumor, metastases, and disseminated tumor cells (DTC). Different classes of radionuclides have been advocated for therapy including ? , ? , and Auger emitters. The different ranges of these radiations in tissue, and their differences in relative biological effectiveness (RBE), contribute to the complexity of predicting therapeutic efficacy. ?However, like external beam radiation therapy, the future of RPT will depend in part on our capacity to plan treatments that maximize therapeutic effect while minimizing adverse effects in normal tissues. Key to the long term success of RPT is to overcome limitations of the intrinsic nonuniform uptake of the radiopharmaceutical by cancer cells that can impact our capacity to sterilize tumors, metastases, and DTC. While primary tumors can often be addressed with external beams of radiation, micrometastases and DTC cannot. While there are commercial tools to assist with calculating absorbed dose to macroscopic disease based on external imaging and using it to predict response, there is a dearth of tools that can be used to optimize and plan RPT of microscopic disease. Only MIRDcell V2, developed in the Howell lab in collaboration with the MIRD Committee in 2014, is widely available. MIRDcell V2 has strengths and weaknesses. This project seeks to overcome many of the weaknesses by creating MIRDcell V3 with new capabilities to facilitate RPT design and treatment planning of micrometastases and DTC. In addition, MIRDcell V3 will serve as an indispensable educational tool for dosimetry and radiobiology of radiopharmaceuticals. Students will be able to operate MIRDcell V3 and learn about how the selection of different radionuclides and other parameters are expected to affect cell killing. The influence of particle range, RBE, activity distribution and other parameters can be explored. In view of the new research that was spurred by its predecessor, MIRDcell V2, this educational element is perhaps one of the most important aspects of MIRDcell V3.
This project will update and expand MIRDcell, a software tool for dosimetry and radiobiology for radiopharmaceutical therapy. The present version MIRDcell v2.1 is powerful, yet has limitations that restrict its use to education and basic science. The work proposed herein will create MIRDcell v3 with expanded capabilities that accommodate patient specific treatment planning for radiopharmaceutical therapies directed against disseminated tumor cells and micrometastases.
