Radiobiologic optimization of combination radiopharmaceutical therapy applied to myeloablative treatment of non-hodgkin lymphoma

Robert F. Hobbs, Richard L. Wahl, Eric C. Frey, Yvette Kasamon, Hong Song, Peng Huang, Richard J. Jones, George Sgouros

Research output: Contribution to journalArticle

Abstract

Combination treatment is a hallmark of cancer therapy. Although the rationale for combination radiopharmaceutical therapy was described in the mid-1990s, such treatment strategies have only been implemented clinically recently and without a rigorous methodology for treatment optimization. Radiobiologic and quantitative imagingbased dosimetry tools are now available that enable rational implementation of combined targeted radiopharmaceutical therapy. Optimal implementation should simultaneously account for radiobiologic normal-organ tolerance while optimizing the ratio of 2 different radiopharmaceuticals required to maximize tumor control. We have developed such a methodology and applied it to hypothetical myeloablative treatment of non-Hodgkin lymphoma (NHL) patients using 131I-tositumomab and 90Y-ibritumomab tiuxetan. Methods: The range of potential administered activities (AAs) is limited by the normal-organ maximum-tolerated biologic effective doses (MTBEDs) arising from the combined radiopharmaceuticals. Dose-limiting normal organs are expected to be the lungs for 131I-tositumomab and the liver for 90Y-ibritumomab tiuxetan in myeloablative NHL treatment regimens. By plotting the limiting normalorgan constraints as a function of the AAs and calculating tumor biologic effective dose (BED) along the normal-organ MTBED limits, we obtained the optimal combination of activities. The model was tested using previously acquired patient normal-organ and tumor kinetic data and MTBED values taken from the literature. Results: The average AA value based solely on normal-organ constraints was 19.0 ± 8.2 GBq (range, 3.9-36.9 GBq) for 131I-tositumomab and 2.77 ± 1.64 GBq (range, 0.42-7.54 GBq) for 90Y-ibritumomab tiuxetan. Tumor BED optimization results were calculated and plotted as a function of AA for 5 different cases, established using patient normal-organ kinetics for the 2 radiopharmaceuticals. Results included AA ranges that would deliver 95% of the maximum tumor BED, allowing for informed inclusion of clinical considerations, such as a maximum-allowable 131I administration. Conclusion: A rational approach for combination radiopharmaceutical treatment has been developed within the framework of a proven 3-dimensional (3D) personalized dosimetry software, 3D-RD, and applied to the myeloablative treatment of NHL. We anticipate that combined radioisotope therapy will ultimately supplant single radioisotope therapy, much as combination chemotherapy has substantially replaced single-agent chemotherapy. COPYRIGHT

Original languageEnglish (US)
Pages (from-to)1535-1542
Number of pages8
JournalJournal of Nuclear Medicine
Volume54
Issue number9
DOIs
StatePublished - Sep 1 2013

Keywords

  • BED
  • Dosimetry
  • Lymphoma
  • Radiopharmaceutical therapy
  • Treatment planning

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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