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Gadolinium Neutron Capture Therapy Using FDA-Approved MRI Contrast Agents

W Swanson1*, S Yasmin-Karim2, V Ainsworth1, N Bih2, R Mueller3, E Sajo1, W Ngwa3, M Jandel1, (1) University of Massachusetts Lowell, Lowell, MA, (2) Dana-Farber Cancer Institute, Boston, MA, (3) Brigham and Womens Hospital, Boston, MA

Presentations

(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library

Purpose: Several decades ago, Boron Neutron Capture Therapy (BNCT) was introduced as a prospective “best of both worlds” treatment modality combining the cancer-targeting mechanisms of chemotherapy and localization methods of radiotherapy. BNCT however suffers from the disadvantage of inducing systemic toxicity. This investigation explores the potential improvement of this modality using locally administered gadolinium (Gd). The significantly greater thermal neutron absorption cross-section of Gd can provide a similar interaction rate to that of boron at a lower dose. By these methods, Gadolinium Neutron Capture Therapy (GdNCT) has the potential to provide non-inferior outcomes with reduced systemic toxicity.


Methods: Ex-vivo experiments were performed on four harvested pancreatic tumors from mice. The tumors were treated with combinations of Gd-based MRI contrast agent (Omniscan) and thermal neutron irradiation equivalent to 4 cGy absorbed dose. Post-treatment DNA damage was assessed by phosphor-histone ?-H2AX stain fluorescence imaging. Experimental results were compared to Geant4 Monte Carlo simulations of dose enhancement in tissue with versus without Gd contrast agent.


Results: ?-H2AX images display a 73% increase in nuclei with radiation-induced double-strand breaks in tissue treated with both Gd and neutron radiation compared to neutron radiation alone. In contrast, computer simulations indicated a dose enhancement ratio of approximately 8.


Conclusion: Both experiments and computations suggest significant radiation sensitization in the presence of Gd. Histone staining exhibited a remarkable degree of additional cell inactivation even at low dose of 4 cGy and using an already FDA-approved MRI contrast agent in concentrations normally used in imaging studies.

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