Targeted radionuclide therapy is being actively investigated as a potential cancer therapy modality. The relationship between absorbed dose and tumor response or normal organ toxicity is important in optimizing radionuclide therapy. Current understanding of this relationship is almost completely derived from external beam rather than radionuclide therapy experience. Using data derived from clinical radionuclide therapy studies we propose to evaluate the potential role of radionuclide dosimetry in trial design and tumor response or toxicity prediction. The following questions will be addressed by this proposal: 1. What is the relationship between estimated absorbed dose and tumor and normal organ response? 2. Does patient specific, 3-D imaging-based dosimetry provide an advantage over a simpler, standard phantom-based approach? 3. Does radiobiologic modeling that accounts for differences in absorbed dose rate and uniformity improve response prediction? 4. How does prior therapy influence hematologic toxicity and the dose-response relationship? Using 3D-ID, a patient-specific 3-D dosimetry package developed by the PI with previous NIH support, the following aims are proposed to address these questions 1.Incorporate radiobiologic modeling in 3D-ID to utilize and interpret dose-rate and spatial uniformity information in evaluating response probability. 2.1.Obtain dose-response relationships in thyroid disease patients treated with 1-131. 2.2. Obtain dose-response relationships for non-hodgkins lymphoma patients treated with non- myeloablative Tositumomab (Bexxar;131l-anti-CD20) and Ibritumomab Tiuxetan (Zevalin;90Y-anti-CD20). 3. Compare dose-responserelationships obtained by accounting for dose-rate, non-uniformity and patient- specific anatomy (i.e., using 3D-ID) with those obtained using a simpler, standard-phantom based methodology (OLINDA);in the NHL studies, evaluate the role of FL.T3 ligand in improving thedose-response relationship for hematologic toxicity. Dosimetry has been assumed to be the best predictor of response following radionuclide treatment. Standardized, rigorous dosimetric analyses of radionuclide therapy data are needed to evaluate this assumption, identify the level of complexity required and to understand how other factors can impact the absorbed dose vs response relationship.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA116477-05
Application #
7790587
Study Section
Special Emphasis Panel (ZRG1-ONC-G (02))
Program Officer
Deye, James
Project Start
2006-05-01
Project End
2011-07-31
Budget Start
2010-04-01
Budget End
2011-07-31
Support Year
5
Fiscal Year
2010
Total Cost
$304,855
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Plyku, Donika; Hobbs, Robert F; Huang, Kevin et al. (2017) Recombinant Human Thyroid-Stimulating Hormone Versus Thyroid Hormone Withdrawal in 124I PET/CT-Based Dosimetry for 131I Therapy of Metastatic Differentiated Thyroid Cancer. J Nucl Med 58:1146-1154
Fahey, Frederic H; Goodkind, Alison B; Plyku, Donika et al. (2017) Dose Estimation in Pediatric Nuclear Medicine. Semin Nucl Med 47:118-125
Yoshida, Takahiro; Jin, Kideok; Song, Hong et al. (2016) Effective treatment of ductal carcinoma in situ with a HER-2- targeted alpha-particle emitting radionuclide in a preclinical model of human breast cancer. Oncotarget 7:33306-15
O'Reilly, Shannon E; Plyku, Donika; Sgouros, George et al. (2016) A risk index for pediatric patients undergoing diagnostic imaging with (99m)Tc-dimercaptosuccinic acid that accounts for body habitus. Phys Med Biol 61:2319-32
Woliner-van der Weg, Wietske; Schoffelen, Rafke; Hobbs, Robert F et al. (2015) Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy. EJNMMI Phys 2:5
Banerjee, Sangeeta Ray; Foss, Catherine A; Pullambhatla, Mrudula et al. (2015) Preclinical evaluation of 86Y-labeled inhibitors of prostate-specific membrane antigen for dosimetry estimates. J Nucl Med 56:628-34
Plyku, Donika; Loeb, David M; Prideaux, Andrew R et al. (2015) Strengths and Weaknesses of a Planar Whole-Body Method of (153)Sm Dosimetry for Patients with Metastatic Osteosarcoma and Comparison with Three-Dimensional Dosimetry. Cancer Biother Radiopharm 30:369-79
Sgouros, George; Goldenberg, David M (2014) Radiopharmaceutical therapy in the era of precision medicine. Eur J Cancer 50:2360-3
Sgouros, George; Hobbs, Robert F (2014) Dosimetry for radiopharmaceutical therapy. Semin Nucl Med 44:172-8
Hobbs, Robert F; Howell, Roger W; Song, Hong et al. (2014) Redefining relative biological effectiveness in the context of the EQDX formalism: implications for alpha-particle emitter therapy. Radiat Res 181:90-8

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