ArticlePhysics in medicine and biology2012
A bone marrow toxicity model for ²²³Ra alpha-emitter radiopharmaceutical therapy.
Article in Physics in medicine and biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00667537 (A Phase I, Open-label, Dosimetry, Biodistribution and Pharmacokinetic Study of Alpharadin™ in Patients With Hormone Refractory Prostate Cancer and Skeletal Metastases), which is not on this map. Cited by 45 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I, Open-label, Dosimetry, Biodistribution and Pharmacokinetic Study of Alpharadin™ in Patients With Hormone Refractory Prostate Cancer and Skeletal Metastases
Who cites it
45 citing papers in PubMed.
- Improving the dose-myelotoxicity correlation in radiometabolic therapy of bone metastases with 153Sm-EDTMP.European journal of nuclear medicine and molecular imaging · 2014Trial
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- Embracing the Future of Clinical Trials in Radiation Therapy: An NRG Oncology CIRO Technology Retreat Whitepaper on Pioneering Technologies and AI-Driven Solutions.International journal of radiation oncology, biology, physics · 2025Review
- Beyond Average: α-Particle Distribution and Dose Heterogeneity in Bone Metastatic Prostate Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024Article
- The value of baseline 18F-sodium fluoride and 18F-choline PET activity for identifying responders to radium-223 treatment in castration-resistant prostate cancer bone metastases.European radiology · 2024Article
- Heterogeneity of dose distribution in normal tissues in case of radiopharmaceutical therapy with alpha-emitting radionuclides.Radiation and environmental biophysics · 2022Review
- MIRD Pamphlet No. 27: MIRDcell V3, a Revised Software Tool for Multicellular Dosimetry and Bioeffect Modeling.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022Article
- Radionuclides for Targeted Therapy: Physical Properties.Molecules (Basel, Switzerland) · 2022Review
- Blind Image Restoration Enhances Digital Autoradiographic Imaging of Radiopharmaceutical Tissue Distribution.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022Article
- Imaging and dosimetry for alpha-particle emitter radiopharmaceutical therapy: improving radiopharmaceutical therapy by looking into the black box.European journal of nuclear medicine and molecular imaging · 2021Review
- Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Article
- Evaluation of Aminopolycarboxylate Chelators for Whole-Body Clearance of FreePharmaceutics · 2021Article
- Effect of microdistribution of alpha and beta-emitters in targeted radionuclide therapies on delivered absorbed dose in a GATE model of bone marrow.Physics in medicine and biology · 2021Article
- Modeling bystander effects that cause growth delay of breast cancer xenografts in bone marrow of mice treated with radium-223.International journal of radiation biology · 2021Article
- Radiopharmaceutical therapy in cancer: clinical advances and challenges.Nature reviews. Drug discovery · 2020Review
- A phase II randomized trial of RAdium-223 dichloride and SABR Versus SABR for oligomEtastatic prostate caNcerS (RAVENS).BMC cancer · 2020Article
- Dosimetry, Radiobiology and Synthetic Lethality: Radiopharmaceutical Therapy (RPT) With Alpha-Particle-Emitters.Seminars in nuclear medicine · 2020Review
- Internal microdosimetry of alpha-emitting radionuclides.Radiation and environmental biophysics · 2020Review
- Dose-Dependent Growth Delay of Breast Cancer Xenografts in the Bone Marrow of Mice Treated withJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020Article
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Authors and funding
8 authors.
Funding
Abstract
Ra-223, an α-particle emitting bone-seeking radionuclide, has recently been used in clinical trials for osseous metastases of prostate cancer. We investigated the relationship between absorbed fraction-based red marrow dosimetry and cell level-dosimetry using a model that accounts for the expected localization of this agent relative to marrow cavity architecture. We show that cell level-based dosimetry is essential to understanding potential marrow toxicity. The GEANT4 software package was used to create simple spheres representing marrow cavities. Ra-223 was positioned on the trabecular bone surface or in the endosteal layer and simulated for decay, along with the descendants. The interior of the sphere was divided into cell-size voxels and the energy was collected in each voxel and interpreted as dose cell histograms. The average absorbed dose values and absorbed fractions were also calculated in order to compare those results with previously published values. The absorbed dose was predominantly deposited near the trabecular surface. The dose cell histogram results were used to plot the percentage of cells that received a potentially toxic absorbed dose (2 or 4 Gy) as a function of the average absorbed dose over the marrow cavity. The results show (1) a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity; and (2) that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity resulted in only a small increase in potential marrow toxicity (i.e. the number of cells receiving more than 4 or 2 Gy), for a range of average marrow cavity absorbed doses from 1 to 20 Gy. The results from the trabecular model differ markedly from a standard absorbed fraction method while presenting comparable average dose values. These suggest that increasing the amount of radioactivity may not substantially increase the risk of toxicity, a result unavailable to the absorbed fraction method of dose calculation.
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