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Monte Carlo Simulation of Radiation Transport and Dose Deposition From Locally Released Radiolabeled Gold Nanoparticles Incorporated Into Tissue Implantable Depots

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P Lai

P Lai1*, Z Cai2 , J Pignol3 , D Jaffray4 , R Reilly5 , (1) University of Toronto, Toronto, Ontario, Canada(2) University of Toronto, Toronto, Ontario, Canada (3) Erasmus MC, Rotterdam, Netherlands(4) University Health Network, Toronto, Ontario, Canada(5) University of Toronto, Toronto, Ontario, Canada


TU-D-205-7 (Tuesday, August 1, 2017) 11:00 AM - 12:15 PM Room: 205

Purpose: Gold nanoparticles (AuNP) functionalized with electron emitting radionuclides have recently been developed for treatment of various cancers, however limited studies have explored the dose distribution from such an agent. Previously, we reported a novel nanoparticle depot (NPD) that can be delivered interstitially using permanent brachytherapy techniques and control release of AuNP in the tumor. The use of NPD may offer a dosimetric advantage by providing a way to spatially design and administer prescription doses of radiolabeled-AuNP. The aim of the current study is to report the three dimensional dose distribution resulting from radiolabeled-AuNP administered by NPD and intratumoral (i.t) injection, using Monte Carlo based voxel level dosimetry.

Methods: ¹⁷⁷Lu-AuNP were constructed and incorporated into NPD. C.B-17 SCID mice bearing MDA-MB-231 human breast cancer xenografts were implanted with ¹⁷⁷Lu-AuNP NPD, or i.t. injected with ¹⁷⁷Lu-AuNP in d.d.H2O. Activity distributions of ¹⁷⁷Lu-AuNP within the tumors were derived from micro-SPECT imaging (1h, 24h, 48h, 7d). The MCNP5 Monte Carlo code was used to calculate voxel dose kernels comprising of S-values for long-range (⁹⁰Y), mid-range (¹⁷⁷Lu) and short-range (¹¹¹In) electron emitters. Three dimensional dosimetry was performed by convolving activity distributions with voxel dose kernels.

Results: The use of NPD for radiolabeled-AuNP delivery resulted in predictable concentric dose distributions as compared to i.t. injected radiolabeled-AuNP, which were irregular. Dose volume histograms of the VOI indicated that ⁹⁰Y was the most robust for achieving a homogeneous dose distribution while compensating for heterogeneities in the activity distribution. At 1h, the minimum dose rate within the VOI were a factor of 4×10² (¹⁷⁷Lu) and 1.3×10⁵ (¹¹¹In) lower than ⁹⁰Y (2×10⁻⁵ Gy/Bq∙s).

Conclusion: NPD offers a clinically practical method of delivering radiolabeled AuNP for treatment of localized cancers using existing brachytherapy techniques. Further optimization may allow homogeneous delivery of doses from electron emitting radionuclides with shorter penetrating ranges.

Funding Support, Disclosures, and Conflict of Interest: This research was supported by a grant from the Canadian Breast Cancer Foundation (CBCF), Ontario Region to R.M. Reilly and J.P. Pignol. P. Lai is supported by an Alexander Graham Bell Canada Graduate Scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC).

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