Journal article
Targeting CXCR4 with 212Pb/203Pb-Pentixather Significantly Increases Overall Survival in Small Cell Lung Cancer
Radiation research, Vol.204(3), pp.173-183
09/2025
DOI: 10.1667/RADE-24-00232.1
PMCID: PMC12629504
PMID: 40605199
Abstract
Small cell lung cancer (SCLC) has a 6% 5-year overall survival rate. C-X-C chemokine receptor 4 (CXCR4) is an attractive target for theranostic agents, is highly expressed in SCLCs, and can be targeted with pentixather using the theranostic pair 212Pb/203Pb. The hypothesis that 212Pb/203Pb-pentixather can be used safely and effectively for imaging and therapy in SCLC in xenograft models was tested. SPECT-CT imaging and biodistribution studies of tumor-bearing mice injected with 203Pb-pentixather demonstrated CXCR4 expression-dependent uptake and accumulation of radioligand in the kidneys and livers. Dosimetry calculations were performed to estimate 212Pb-pentixather uptake in tumor and normal tissue. 212Pb-Pentixather treatment (37-111 kBq/g) of SCLC xenografts (DMS273 and H69AR) significantly prolonged survival and delayed tumor growth. CBCs of mice at 30 days after treatment demonstrated adequate retention of bone marrow function. NSG mice allografted with human hCD34+ bone marrow were treated with 212Pb-pentixather (37-111 kBq/g) to assess damage to human hematopoietic stem cells, demonstrating cytopenias in peripheral blood CBCs at 13-18 days after treatment, resolving by days 28-31. Flow cytometry of bone marrow in these animals at days 28-31 demonstrated a significantly reduced frequency of the human hematopoietic marker CD45 and reconstitution of the bone marrow with murine CD45+ lineages. 203Pb-Pentixather can be used to image CXCR4-expressing SCLC xenografts. Treatment with high-LET alpha emitter 212Pb-pentixather significantly prolonged overall survival, and recovery of mouse bone marrow from 212Pb-pentixather was significantly greater than that of human bone marrow.
Details
- Title: Subtitle
- Targeting CXCR4 with 212Pb/203Pb-Pentixather Significantly Increases Overall Survival in Small Cell Lung Cancer
- Creators
- Keegan A Christensen - Free Radical and Radiation Biology Program, Department of Radiation Oncology, and Departments ofMelissa A Fath - Free Radical and Radiation Biology Program, Department of Radiation Oncology, and Departments ofJordan T Ewald - PediatricsClaudia Robles-Planells - PediatricsStephen A Graves - RadiologySpenser S Johnson - Free Radical and Radiation Biology Program, Department of Radiation Oncology, and Departments ofZeb R Zacharias - University of IowaJon C D Houtman - University of IowaM Sue O'Dorisio - PediatricsMichael K Schultz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, and Departments ofBryan G Allen - Free Radical and Radiation Biology Program, Department of Radiation Oncology, and Departments ofMuhammad Furqan - Internal MedicineYusuf Menda - RadiologyDijie Liu - PediatricsDouglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, and Departments of
- Resource Type
- Journal article
- Publication Details
- Radiation research, Vol.204(3), pp.173-183
- DOI
- 10.1667/RADE-24-00232.1
- PMID
- 40605199
- PMCID
- PMC12629504
- NLM abbreviation
- Radiat Res
- ISSN
- 0033-7587
- eISSN
- 1938-5404
- Publisher
- RADIATION RESEARCH SOC
- Grant note
- NIH: CA243014, CA243693, CA217797, CA244091, CA270742, P50 CA174521, CA086862 Carver College of MedicineIowa City Veterans Administration Medical CenterNational Cancer Institute of the National Institutes of Health: P30CA086862
This work was supported in part by NIH grants CA243014, CA243693, CA217797, CA243693, CA244091, CA270742, P50 CA174521 and CA086862. Data presented herein were generated by the Human Immunology Core and obtained at the Flow Cytometry Facility, and statistics were performed with the help of the Biostatistics Core, which are Carver College of Medicine/Holden Comprehensive Cancer Center core research facilities at the University of Iowa. These facilities are funded through user fees and the generous financial support of the Carver College of Medicine, Holden Comprehensive Cancer Center, and Iowa City Veterans Administration Medical Center. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA086862. 12 Pb-Pentixather and 203 Pb-pentixather were obtained as a generous gift from Perspective Therapeutics.
- Language
- English
- Electronic publication date
- 07/03/2025
- Date published
- 09/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Microbiology and Immunology; Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984843246902771
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