Abstract
Radiopharmaceutical therapy is growing rapidly. However, yet to be addressed is the implementation of methods to plan treatments for circulating tumor cells, disseminated tumor cells, and micrometastases. Given the capacity of radiopharmaceuticals to specifically target and kill single cells and multicellular clusters, a quality not available in chemotherapy and external-beam radiation therapy, it is important to develop dosimetry and bioeffect modeling tools that can inform radiopharmaceutical design and predict their effect on microscopic disease. This pamphlet describes a new version of MIRDcell, a software tool that was initially released by the MIRD committee several years ago. Methods: Version 3 (V3) of MIRDcell uses a combination of analytic and Monte Carlo methods to conduct dosimetry and bioeffect modeling for radiolabeled cells within planar colonies and multicellular clusters. A worked example is provided to assist users to learn old and new features of MIRDcell and test its capacity to recapitulate published responses of tumor cell spheroids to radiopharmaceutical treatments. Prominent capabilities of the new version include radially dependent activity distributions, user-imported activity distributions, cold regions within the cluster, complex bioeffect modeling that accounts for radiation type and subcellular distribution, and a rich table of output data for subsequent analysis. Results: MIRDcell V3 effectively reproduces experimental responses of multicellular spheroids to uniform and nonuniform distributions of therapeutic radiopharmaceuticals. Conclusion: MIRDcell is a versatile software tool that can be used for educational purposes and design of radiopharmaceutical therapies.
Highlights
The widespread use of 223Ra dichloride (Xofigo®) and 177Lu-DOTATATE (LUTATHERA®) has rejuvenated radiopharmaceutical therapy (RPT) of cancer
MIRDcell is a versatile software tool that can be used for educational purposes and design of radiopharmaceutical therapies. 3
It can be seen from both plots that the data are better represented by the MIRDcell prediction than the single component exponential fit used by Kennel et al [21]
Summary
The widespread use of 223Ra dichloride (Xofigo®) and 177Lu-DOTATATE (LUTATHERA®) has rejuvenated radiopharmaceutical therapy (RPT) of cancer. RPT delivers radioactive drugs to the primary tumor, metastases, disseminated tumor cells (DTC), and circulating tumor cells (CTC). The different ranges of these radiations in tissue, and their differences in relative biological effectiveness (RBE), contribute to the complexity of predicting therapeutic efficacy and normal tissue toxicity [1]. Like external beam radiation therapy (EBRT), 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 implement strategies that overcome limitations of the intrinsic nonuniform uptake of radiopharmaceuticals by cancer cells that can impact our capacity to sterilize tumors, metastases, DTC, and CTC
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