Price A Jackson1,2, Michael S Hofman3,2, Rodney J Hicks3,2, Mark Scalzo3, John Violet4. 1. Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia price.jackson@petermac.org. 2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; and. 3. Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia. 4. Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
Abstract
Calculation of radiation dosimetry in targeted nuclear medicine therapies is traditionally resource-intensive, requiring multiple posttherapy SPECT acquisitions. An alternative approach is to take advantage of existing pharmacokinetic data from these smaller cohorts to enable dose computation from a single posttreatment scan in a manner that may be applied to a much broader patient population. Methods: In this work, a technical description of simplified dose estimation is presented and applied to the assessment of 177Lu-prostate-specific membrane antigen (PSMA)-617 therapy for metastatic prostate cancer. By normalizing existing time-activity curves to a single measurement time, it is possible to calculate a mean and range of time-integrated activity values that relate to absorbed radiation dose. To assist with accurate pharmacokinetic modeling of the training cohort, a method for contour-guided image registration was developed. Results: Tissue-specific dose conversion factors for common posttreatment imaging times are reported along with a characterization of added uncertainty in comparison to a traditional serial imaging protocol. Single-time-point dose factors for tumor were determined to be 11.0, 12.1, 13.6, and 15.2 Gy per MBq/mL at image times of 24, 48, 72, and 96 h, respectively. For normal tissues, parotid gland factors were 6.7, 9.4, 13.3, and 19.3 Gy per MBq/mL at those times, and kidneys were 7.1, 10.3, 15.0, and 22.0 Gy per MBq/mL. Tumor dose estimates were most accurate using delayed scanning at times beyond 72 h. Dose to healthy tissues is best characterized by scanning patients in the first 2 d of treatment because of the larger degree of tracer clearance in this early phase. Conclusion: This work demonstrates a means for efficient dose estimation in 177Lu-PSMA-617 therapy. By providing methods to simplify and potentially automate radiation dosimetry, we hope to accelerate the understanding of radiobiology and development of dose-response models in this unique therapeutic context.
Calculation of radiation dosimetry in targeted nuclear medicine therapies is traditionally resource-intensive, requiring multiple posttherapy SPECT acquisitions. An alternative approach is to take advantage of existing pharmacokinetic data from these smaller cohorts to enable dose computation from a single posttreatment scan in a manner that may be applied to a much broader patient population. Methods: In this work, a technical description of simplified dose estimation is presented and applied to the assessment of 177Lu-prostate-specific membrane antigen (PSMA)-617 therapy for metastatic prostate cancer. By normalizing existing time-activity curves to a single measurement time, it is possible to calculate a mean and range of time-integrated activity values that relate to absorbed radiation dose. To assist with accurate pharmacokinetic modeling of the training cohort, a method for contour-guided image registration was developed. Results: Tissue-specific dose conversion factors for common posttreatment imaging times are reported along with a characterization of added uncertainty in comparison to a traditional serial imaging protocol. Single-time-point dose factors for tumor were determined to be 11.0, 12.1, 13.6, and 15.2 Gy per MBq/mL at image times of 24, 48, 72, and 96 h, respectively. For normal tissues, parotid gland factors were 6.7, 9.4, 13.3, and 19.3 Gy per MBq/mL at those times, and kidneys were 7.1, 10.3, 15.0, and 22.0 Gy per MBq/mL. Tumor dose estimates were most accurate using delayed scanning at times beyond 72 h. Dose to healthy tissues is best characterized by scanning patients in the first 2 d of treatment because of the larger degree of tracer clearance in this early phase. Conclusion: This work demonstrates a means for efficient dose estimation in 177Lu-PSMA-617 therapy. By providing methods to simplify and potentially automate radiation dosimetry, we hope to accelerate the understanding of radiobiology and development of dose-response models in this unique therapeutic context.
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