Multi-regional dosimetry of mouse kidneys for beta-emitters

Aim/Introduction: Conventional preclinical internal dose estimates typically assume a uniform distribution of radioactivity and dose deposition throughout organ tissues. This assumption can deviate from reality for β-/α-emitting radioligands with a heterogeneous tissue activity distribution. In this study S-values for internal dosimetry of β- emitters were calculated for a multi-region model of a mouse kidney. The significance of regional S-values was demonstrated for the mouse kidney biodistribution of a 131I-labeled single-domain anti-HER2 antibody fragment with predominant uptake in the outer stripe of the outer medulla. Materials and Methods: A stylized computational model of a mouse kidney was developed, consisting on ellipsoids delimiting 5 tissue compartments: renal cortex, outer medulla outer/inner stripes (IS/OS), inner medulla and papilla. Energy absorbed fractions (ɸ) for the different kidney regions were calculated for 131I and 90Y, from photon-electron transport simulations using MCNP6.2 code. A sensitivity study on the influence of model specifications (kidney volume, cortex occupancy) was performed. For the 131I mouse study, time-dependent regional kidney-tissue activities were determined from the relative regional activity concentrations of kidney sections measured with digital β--particle autoradiography (using an iQID system), relative to the whole-kidney activity measured with conventional gamma counting. Results: For 131I, a large fraction of the emitted β- energy is absorbed within the sub-kidney source region itself (ɸ ≥0.60). Because of this and the smaller masses of sub-kidney tissues, the self-irradiation regional S-values are considerably higher (30% to >200% depending on kidney region) than whole-kidney S-values. Compared to 131I, 90Y regional self-absorbed fractions are lower (ɸ <0.35). Yet, the difference between self-irradiation regional and whole-kidney S-values is still very large (≥100%) for most renal tissues. β- cross-irradiation is significant (ɸ often >0.10) between most regions for 90Y and between adjacent regions for 131I (e.g. cortex/OS, OS/IS). The sensitivity of self-absorbed fractions to the kidney model specifications was typically small for 131I (<5% deviation between models) and moderate for 90Y (<20%). For the 131I mouse study, regional dose rates and time-integrated doses based on a heterogeneous activity distribution differ largely (-60% to >100% depending on region) from the uniform whole-kidney dose based on a homogeneous activity distribution. Conclusion: The calculated regional S-values, in combination with sub-kidney activity information, allow a more realistic estimation of the doses absorbed by different renal tissues from β--emitting radioligands with a heterogeneous kidney uptake. This provides new dose information relevant for preclinical investigations studying the risk of radiation-induced nephrotoxicity of these therapies.