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Evaluation of CD44v6-targeted radionuclide therapy on bone marrow, skin and esophageal epithelium using a novel internal dosimetry model
Sahlgrens Acad, Inst Clin Sci, Dept Med Radiat Sci, Gothenburg, Sweden..
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.ORCID iD: 0000-0003-4662-3142
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..ORCID iD: 0000-0002-6771-3289
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-6421-4142
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2025 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 70, no 23, article id 235031Article in journal (Refereed) Published
Abstract [en]

Objective. The cell surface antigen CD44v6 is a promising target for several cancers, with favorable in vivo characteristics such as high affinity and suitable biodistribution. In normal tissues, expressions are restricted to basal epithelial cells in skin and mucosa. Consequently, previous clinical studies have reported varying degrees of toxicity in these tissues. To support new radioimmunotherapies (RIT), we developed small-scale internal dosimetry models for abdominal skin and esophageal mucosa. Using published biodistribution data, we compared absorbed doses to epithelial tissues and bone marrow from four clinically relevant radionuclides: rhenium-186, lutetium-177, terbium-161, and actinium-225. Approach. From the Genotype-Tissue Expression database, 288 H&E-stained sections of abdominal skin and esophageal mucosa were obtained from donors aged 21-70 and segmented to generate voxelized models. Monte Carlo simulations were conducted for the radionuclides across multiple source/target combinations. A compartment model generated serum, skin, and bone marrow biodistributions to estimate AD to the epithelium and bone marrow. Main results. Absorbed dose estimates to the basal layer of the skin were highest for 161Tb at 23.7 Gy GBq-1, followed by 177Lu and 186Re, with values of 9.5 and 5.3 Gy GBq-1, respectively, whereas the alpha emitter 225Ac delivered a dose of 4.9 Gy MBq-1. For the beta-emitters, three methods produced absorbed-dose estimates for the red marrow (RM) consistent within 5% of each other, with the highest values in the hip bone: 0.36, 0.25, and 0.39 Gy GBq-1 for 186Re, 177Lu, and 161Tb, respectively, compared to 0.66 Gy MBq-1 for 225Ac. Significance. This study presents a dosimetry framework for CD44v6-targeted RIT, demonstrating that, at clinically relevant administered activities, short-ranged emitters like 161Tb and 225Ac deliver substantially higher doses to basal epithelial layers compared to 186Re. RM doses were comparable for 161Tb and 186Re, lower for 177Lu, and highly uncertain for 225Ac due to daughter redistribution. Overall, these results support the use of 177Lu for initial clinical trials.

Place, publisher, year, edition, pages
Institute of Physics (IOP), 2025. Vol. 70, no 23, article id 235031
Keywords [en]
small-scale, skin, esophagus, dosimetry, CD44v6, radionuclide therapy
National Category
Radiology and Medical Imaging Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-573639DOI: 10.1088/1361-6560/ae237eISI: 001630937700001PubMedID: 41342241OAI: oai:DiVA.org:uu-573639DiVA, id: diva2:2022525
Funder
Swedish Cancer Society, 22 2391 SSwedish Cancer Society, 24 3485 PjAvailable from: 2025-12-17 Created: 2025-12-17 Last updated: 2025-12-17Bibliographically approved

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Nestor, MarikaLundgren Mortensen, AnjaFrejd, Fredrik

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