Endocrine Abstracts

Aim: Auger electron (AE)-emitting radionuclides are well suited as molecularly targeted radionuclide therapeutics (MRT) due to the high energy deposition density in the immediate vicinity of the decay site which avoids to a large extent non-specific radiotoxicity. However, due to the short range of the low-energy Auger (and Coster-Kronig) electrons, it is imperative that the AE emitting agent is closely associated with the cell nucleus. In this study we evaluate the dose deposition of intra-nuclear accumulated activity using transmission electron microscopy (TEM) images to inform the spatial distribution.

Materials and methods: Q620B head and neck cancer cells were treated with ¹¹¹In-DTPA-hEGF (8 MBq, 40 nM) for 24 h before microautoradiography (MAR) and TEM preparation and analysis. The complete radiation spectra of ¹¹¹In was generated using the BrIccEmis code [1], which implements a stochastic model for the atomic relaxation assuming a condensed-phase approach. Dose-point kernels (DPKs) in 1 nm radial bins were calculated using event-by-event simulations with the general-purpose Monte Carlo (MC) code PENELOPE [2]. The simulated DPKs were then overlaid on the TEM images to form a dosemap.

Results: Quantitative analysis of TEM images noted 44±23.85 and 19.96±13.69 grains per cell in the cytoplasm and nucleus respectively. Energy deposition in the first 1 nm radial bin representing a DNA double helix was 176.6 eV with a corresponding DPK of 6.75 MGy. The dose decreased to 6.85 mGy over the scale of an entire mitotic chromosome (1400 nm).

Conclusion: TEM-MAR is a viable method for looking at the spatial distribution of radioisotopes in single cells. The heterogeneity in spatial distribution resulted in a large variation in dose over the nucleus.

References

[1] Lee B et al. Comp Math Meth Med 2012; 651475.

[2] Salvat F, Fernández-Varea JM, Sempau J, eds. PENELOPE-2011 OECD Nuclear Energy Agency.