A nephron-based model of the kidneys for macro-to-micro α-particle dosimetry

Hobbs, Robert F; Song, Hong; Huso, David L; H Sundel, Margaret; Sgouros, George

doi:10.1088/0031-9155/57/13/4403

Cited by 61Radiopharmaceutical Chemistry and ApplicationsAdvanced Radiotherapy TechniquesRadioactivity and Radon Measurements

A nephron-based model of the kidneys for macro-to-micro α-particle dosimetry

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Hobbs, Robert F, Song, Hong, Huso, David L, H Sundel, Margaret, Sgouros, George·2012·Physics in Medicine and Biology

DOI 10.1088/0031-9155/57/13/4403PMC PMC3640368

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Abstract

Targeted α-particle therapy is a promising treatment modality for cancer. Due to the short path-length of α-particles, the potential efficacy and toxicity of these agents is best evaluated by microscale dosimetry calculations instead of whole-organ, absorbed fraction-based dosimetry. Yet time-integrated activity (TIA), the necessary input for dosimetry, can still only be quantified reliably at the organ or macroscopic level. We describe a nephron- and cellular-based kidney dosimetry model for α-particle radiopharmaceutical therapy, more suited to the short range and high linear energy transfer of α-particle emitters, which takes as input kidney or cortex TIA and through a macro to micro model-based methodology assigns TIA to micro-level kidney substructures. We apply a geometrical model to provide nephron-level S-values for a range of isotopes allowing for pre-clinical and clinical applications according to the medical internal radiation dosimetry (MIRD) schema. We assume that the relationship between whole-organ TIA and TIA apportioned to microscale substructures as measured in an appropriate pre-clinical mammalian model also applies to the human. In both, the pre-clinical and the human model, microscale substructures are described as a collection of simple geometrical shapes akin to those used in the Cristy-Eckerman phantoms for normal organs. Anatomical parameters are taken from the literature for a human model, while murine parameters are measured ex vivo. The murine histological slides also provide the data for volume of occupancy of the different compartments of the nephron in the kidney: glomerulus versus proximal tubule versus distal tubule. Monte Carlo simulations are run with activity placed in the different nephron compartments for several α-particle emitters currently under investigation in radiopharmaceutical therapy. The S-values were calculated for the α-emitters and their descendants between the different nephron compartments for both the human and murine models. The renal cortex and medulla S-values were also calculated and the results compared to traditional absorbed fraction calculations. The nephron model enables a more optimal implementation of treatment and is a critical step in understanding toxicity for human translation of targeted α-particle therapy. The S-values established here will enable a MIRD-type application of α-particle dosimetry for α-emitters, i.e. measuring the TIA in the kidney (or renal cortex) will provide meaningful and accurate nephron-level dosimetry.

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Current 3-dimensional imaging modalities SPECT and PET have the resolution and counting statistics needed to quantify macroscale nonuniformities but not microscale nonuniformities.
“Also related to these nonuniformities is the fact that current 3-dimensional imaging modalities -SPECT and PET -have the resolution and counting statistics needed to quantify macroscale nonuniformities (e.g., kidney renal cortex vs. overall kidney volume) but not assess nonuniformities at the microscale (e.g., renal tubule vs. renal glomerulus) level.”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [11]
The Introduction says the microscale information needed for α-particle dosimetry is smaller than the resolving power of clinical imaging, and the Methods say clinical activity measurements are made at the kidney or, at best, renal-cortex level. These passages support the macro-versus-micro distinction, but our copy does not establish the claim specifically for PET or attribute the limitation to counting statistics. No page numbers were provided for these passages. (LLM, conf=0.84)
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Authors: Hobbs, R. F., Song, H., Huso, D. L., H Sundel, M., & Sgouros, G.
Affiliations: Johns Hopkins University (US)
Corresponding author: Hobbs, Robert F
Huso, David L
Sgouros, George
ORCID: Hobbs, Robert F
Venue: Physics in Medicine and Biology
Publisher: IOP Publishing
Published: 2012-06-15
Volume: 57
Issue: 13
Pages: 4403-4424
ISSN: 0031-9155 (ISSN-L)
1361-6560
DOI: 10.1088/0031-9155/57/13/4403
PMC: PMC3640368
OpenAlex: W2097789626
Cited by: 61
References: 62
Citations by year: 2026: 3 · 2025: 3 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 6 · 2015: 1 · 2014: 6 · 2013: 1
FWCI: 1.93
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Physics in Medicine and Biology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (UL1TR000064)
National Cancer Institute (R01CA157542, R01CA116477)
National Center for Advancing Translational Sciences
Topics: Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
Health Sciences › Health Professions › Radiological and Ultrasound Technology › Radioactivity and Radon Measurements
Keywords: targeted alpha therapy, alpha particle dosimetry, kidney dosimetry, S-values, time-integrated activity, renal cortex, renal medulla, alpha-emitting radionuclides, fraction absorbed, Monte Carlo simulation, glomeruli
MeSH terms: Alpha Particles, Animals, Humans, Models, Biological, Monte Carlo Method, Nephrons, Radiometry, Phantoms, Imaging, Mice

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A nephron-based model of the kidneys for macro-to-micro α-particle dosimetry

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