Cellular dosimetry of ¹⁹⁷Hg, ^197mHg and ¹¹¹In: comparison of dose deposition and identification of the cell and nuclear membrane as important targets

Abstract

Purpose

To examine the reliability to model cellular S-values for the Auger electron (AE) emitters, ¹¹¹In, ¹⁹⁷Hg and ^197mHg with MCNP6 and their relative dose deposition in subcellular targets.

Methods

A model cell was defined as four concentric spheres consisting of the nucleus (N), cytoplasm (Cy), cell and nuclear membranes (CM, NM) in which radionuclides distributed homogeneously. The transport of AE, conversion electrons and photons were simulated by MCNP6 to calculate cellular S values (S_N←CM, S_N←Cy, S_N←NM, S_N←N, S_CM←CM, S_NM←NM). S_N←CM, S_N←Cy and S_N←N were also calculated with MIRDcell.

Results

MIRDcell and MCNP6-calculated S_N←N were in excellent agreement, but a slight discrepancy on S_N←Cy and S_N←CM was observed. The ratios of S_CM←CM or S_NM←NM vs. S_N←N were 9.7–51.0 or 10.5–37.4, 7.9–41.8 or 8.4–31.8 and 7.2–36.9 or 8.0–28.1 for ¹¹¹In, ¹⁹⁷Hg, ^197mHg, respectively. The mean S(¹⁹⁷Hg)/S(¹¹¹In) and S(^197mHg)/S(¹¹¹In) were 2.5 ± 0.5 and 2.5 ± 0.6, respectively.

Conclusions

Cellular S-values were reliably calculated with MCNP6. ¹⁹⁷Hg and ^197mHg deposit two-fold more doses than ¹¹¹In at the subcellular scale. All AE emitters deposit a higher self-dose in the CM and NM than in the N, which warrants studies on the effects of targeting the CM and NM by AE emitters.

Keywords:

• ¹⁹⁷Hg
• ^197mHg
• ¹¹¹In
• Auger electrons
• dosimetry

Acknowledgments

The authors would like to thank and acknowledge the collaboration with Drs. Valery Radchenko and Cornelia Hoehr at TRIUMF (Vancouver, B.C., Canada) for their efforts in producing ¹⁹⁷Hg and ^197mHg for the cancer treatment which motivated this study on the dosimetry of these radionuclides.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by a Discovery grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) under Grant [#RGPIN-2020-04496] and an Innovation grant from the Canadian Cancer Society under Grant [#706774] to RMR and ZC. NA received funding from the PRiME Precision Medicine Initiative at the University of Toronto. CG was supported by the NSERC Polymer Nanoparticles for Drug Delivery (POND) CREATE training program and an MDS Nordion Scholarship in Radiopharmaceutical Sciences from the University of Toronto.

Notes on contributors

Zhongli Cai

Dr. Zhongli Cai is a senior research associate at the Leslie Dan Faculty of Pharmacy, University of Toronto. Her current research includes fundamental studies of the effects of Auger electrons emitted in different subcellular compartments of human cells, Auger electron radioimmunotherapy for treatment and prevention of metastases from triple-negative breast cancer (TNBC), radiation nanomedicine for local treatment of metastases from TNBC and radiation nanomedicine combined with checkpoint immunotherapy for treatment of glioblastoma multiforme (GBM) with a special interest in dosimetry. She holds a PhD in radiobiology from the Université de Sherbrooke and a PhD in radiochemistry from Peking University.

Noor Al-saden

Dr. Noor Al-saden is a molecular imaging and radiopharmaceutical scientist. She is serving as a scientific lead for several projects at STTARR Innovation Center, University Health Network, Toronto, which involve development of imaging probes for PET and SPECT imaging. At the time of this study, Dr. Al-saden was a post-doctoral fellow in the PRiME precision medicine initiative at the University of Toronto working on a radiation nanomedicine for intraoperative treatment of GBM using ¹⁹⁷Hg and ^197mHg. She holds a PhD in Pharmaceutical Sciences from the University of Toronto where she obtained extensive experience in developing PET probes for predicting the delivery of biologically targeted drugs to tumors.

Constantine J. Georgiou

Constantine J. Georgiou is a PhD candidate in the Department of Pharmaceutical Sciences at the University of Toronto. He received a B.Sc. degree in Pharmaceutical Chemistry from the University of Toronto in 2018. His graduate thesis involves developing a radiation nanomedicine for local treatment of GBM.

Raymond M. Reilly

Dr. Raymond M. Reilly is a professor and Director of the Center for Pharmaceutical Oncology at the Leslie Dan Faculty of Pharmacy, University of Toronto. He leads a program of translational radiopharmaceutical research aimed at the development of novel molecular imaging agents and targeted radiotherapeutics for cancer and advancement of the most promising agents to first-in-humans Phase 1 clinical trials in collaboration with oncologists and nuclear medicine imaging specialists. He obtained a BSc in pharmacy and MSc in nuclear pharmacy from the University of Toronto and practiced as a nuclear pharmacist. He subsequently received his PhD in medical biophysics from the University of Toronto focused on the development of Auger electron-emiting radiopharmaceuticals for breast cancer. He supervises MSc and PhD graduate students studying radiopharmaceuticals for cancer imaging and treatment for their thesis research and teaches undergraduate courses in pharmaceutical analysis and clinical laboratory medicine and medical imaging and a graduate course on radiopharmaceutical science.