Targeted radiotherapy with internally administered radiopharmaceuticals has recently experienced renewed interest due to identification of better tumor biomarkers and development of new targeting agents. In any form of radiotherapy, the fraction of surviving cells, healthy organ toxicity and tumor response depend primarily on the quantity of energy deposited. The relationship between absorbed dose and malignant tissue response or normal tissue toxicity is the theme of any radiotherapy approach. The following questions will be addressed by this proposal: 1. Can we improve the accuracy of radiation absorbed dose estimate to a specific patient relative to current, simpler phantom-based methods, yet such a method be efficient enough for routine clinical use? 2) Will accounting for the temporal and spatial dose-rate gradient and tissue-response heterogeneity by using known radiobiologic models improve the predictive value of treatment efficacy and toxicity to bone marrow and kidney? Using an ultra fast discrete ordinate method (DOM) with quantitative SPECT/CT voxel-based dose engine developed by the PI with previous NIH support, the following aims are proposed to address these questions: 1) Validate the accuracy of DOM-QSPECT/CT in phantom with measurements and Monte Carlo simulations, 2) Incorporate known radiobiological effect dose (BED) models in the DOM-QSPECT/CT dose estimate and generate BED-volume-histograms for kidney, 3) Compare retrospectively DOM-QSPECT/CT dose estimates to MIRD and Monte Carlo dose estimates for a cohort of patients treated using Sm-153 EDTMP in a phase II clinical trial, and 4) Correlate the clinical outcomes (bone pain index and toxicity level to bone and kidney) to the DOM-QSPECT/CT-BED dose estimates. The proposed work is innovative because it capitalizes on a novel method to perform radiation transport in human tissue, a method that we have demonstrated to be as accurate as Monte Carlo simulations yet far more efficient for complex external beam radiotherapy regimens (i.e., computational results can be obtained within minutes compared to many hours or days for Monte Carlo). In addition, we propose the incorporation of radiobiological modeling to assess the treatment plan using the biological effective dose concept. With respect to expected outcomes, the combination of the work proposed in the four specific aims is expected to create a new platform for radiopharmaceutical dosimetry that will have a positive impact on the therapy field of nuclear medicine, in a way that will fundamentally advance the field of patient-specific internal radionuclide therapy treatment planning.

Public Health Relevance

Targeted radiotherapy with internally administered radiopharmaceuticals has recently experienced renewed interest due to identification of better tumor biomarkers and development of new targeting agents. Our long term goal is to develop targeted radionuclide therapy planning tools comparable to those used in radiation oncology practice (e.g., for external beam and brachytherapy), in order to aid in trial design and tumor response and toxicity prediction, as well as replace the current, inferior planar image/MIRD-based dosimetry methodology. We developed a deterministic radiation transport method that we plan to validate and test in a cohort of patients from a phase II clinical trial of a skeletal targeted therapy radiopharmaceutical in Breast Cancer Patients with Bone Only Metastases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA138986-01A2
Application #
7888739
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Deye, James
Project Start
2010-08-05
Project End
2013-07-31
Budget Start
2010-08-05
Budget End
2011-07-31
Support Year
1
Fiscal Year
2010
Total Cost
$326,165
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Radiation-Diagnostic/Oncology
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Kappadath, S Cheenu; Mikell, Justin; Balagopal, Anjali et al. (2018) Hepatocellular Carcinoma Tumor Dose Response After 90Y-radioembolization With Glass Microspheres Using 90Y-SPECT/CT-Based Voxel Dosimetry. Int J Radiat Oncol Biol Phys 102:451-461
Siman, W; Mawlawi, O R; Mikell, J K et al. (2017) Effects of image noise, respiratory motion, and motion compensation on 3D activity quantification in count-limited PET images. Phys Med Biol 62:448-464
Mikell, Justin; Cheenu Kappadath, S; Wareing, Todd et al. (2016) Evaluation of a deterministic grid-based Boltzmann solver (GBBS) for voxel-level absorbed dose calculations in nuclear medicine. Phys Med Biol 61:4564-82
Mikell, Justin K; Mahvash, Armeen; Siman, Wendy et al. (2016) Selective Internal Radiation Therapy With Yttrium-90 Glass Microspheres: Biases and Uncertainties in Absorbed Dose Calculations Between Clinical Dosimetry Models. Int J Radiat Oncol Biol Phys 96:888-896
Siman, W; Mikell, J K; Kappadath, S C (2016) Practical reconstruction protocol for quantitative (90)Y bremsstrahlung SPECT/CT. Med Phys 43:5093
Mikell, Justin K; Mahvash, Armeen; Siman, Wendy et al. (2015) Comparing voxel-based absorbed dosimetry methods in tumors, liver, lung, and at the liver-lung interface for (90)Y microsphere selective internal radiation therapy. EJNMMI Phys 2:16
Mikell, Justin K; Klopp, Ann H; Gonzalez, Graciela M N et al. (2012) Impact of heterogeneity-based dose calculation using a deterministic grid-based Boltzmann equation solver for intracavitary brachytherapy. Int J Radiat Oncol Biol Phys 83:e417-22