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HER2 expression in different cell lines at different inoculation sites assessed by [52Mn]Mn-DOTAGA(anhydride)-trastuzumab

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Title: HER2 expression in different cell lines at different inoculation sites assessed by [52Mn]Mn-DOTAGA(anhydride)-trastuzumab
Authors: Toàn Minh Ngô, Adrienn Vágner, Gábor Nagy, Gábor Ország, Tamás Nagy, Zoltán Szoboszlai, Csaba Csikos, Balázs Váradi, György Trencsényi, Gyula Tircsó, Ildikó Garai
Source: Pathology and Oncology Research, Vol 31 (2025)
Publisher Information: Frontiers Media S.A., 2025.
Publication Year: 2025
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
LCC:Pathology
Subject Terms: breast cancer, HER2, trastuzumab, positron emission tomography, 52Mn, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Pathology, RB1-214
Description: PurposePositron emission tomography (PET) hybrid imaging targeting HER2 requires antibodies labelled with longer half-life isotopes. With a suitable radiation profile, 52Mn coupled with DOTAGA as a bifunctional chelator is a potential candidate. In this study, we investigated the tumor HER2 specificity and the temporal biodistribution of the [52Mn]Mn-DOTAGA(anhydride)-trastuzumab in preclinical models.MethodsPET/MRI and PET/CT were performed on SCID mice bearing orthotopic and ectopic HER2-positive and ectopic HER2-negative tumors at 4, 24, 48, 72, and 120 h post-injection with [52Mn]Mn-DOTAGA(anhydride)-trastuzumab. Melanoma xenografts were included for comparison of specificity.ResultsIn vivo biodistribution demonstrated strong contrast in HER2-positive tumors, particularly in orthotopic tumors, where uptake was significantly higher than in the blood pool and other organs from 24 h onwards and consistently higher than in ectopic HER2-positive tumors at all time points. Significantly higher tumor-to-blood and tumor-to-muscle ratios were observed in HER2-positive ectopic tumors compared to HER2-negative tumors but only at 4 and 24 h; the differences were likely due to non-specific binding of the tracer. The ratios for orthotopic HER2-positive tumors were significantly higher than those for ectopic HER2-negative tumors and melanoma at all time points. However, the differences between HER2-positive and HER2-negative tumors decreased at later time points.ConclusionThese results suggest that [52Mn]Mn-DOTAGA(anhydride)-trastuzumab demonstrates efficient tumor-to-background contrast, emphasize the higher tumor uptake observed in orthotopic tumors, and highlight the influence of tumor environment characteristics on uptake.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1532-2807
Relation: https://www.por-journal.com/articles/10.3389/pore.2025.1611999/full; https://doaj.org/toc/1532-2807
DOI: 10.3389/pore.2025.1611999
Access URL: https://doaj.org/article/b63bc38e559c4b559444e58bbd8f6bae
Accession Number: edsdoj.b63bc38e559c4b559444e58bbd8f6bae
Database: Directory of Open Access Journals
Description
Abstract:PurposePositron emission tomography (PET) hybrid imaging targeting HER2 requires antibodies labelled with longer half-life isotopes. With a suitable radiation profile, 52Mn coupled with DOTAGA as a bifunctional chelator is a potential candidate. In this study, we investigated the tumor HER2 specificity and the temporal biodistribution of the [52Mn]Mn-DOTAGA(anhydride)-trastuzumab in preclinical models.MethodsPET/MRI and PET/CT were performed on SCID mice bearing orthotopic and ectopic HER2-positive and ectopic HER2-negative tumors at 4, 24, 48, 72, and 120 h post-injection with [52Mn]Mn-DOTAGA(anhydride)-trastuzumab. Melanoma xenografts were included for comparison of specificity.ResultsIn vivo biodistribution demonstrated strong contrast in HER2-positive tumors, particularly in orthotopic tumors, where uptake was significantly higher than in the blood pool and other organs from 24 h onwards and consistently higher than in ectopic HER2-positive tumors at all time points. Significantly higher tumor-to-blood and tumor-to-muscle ratios were observed in HER2-positive ectopic tumors compared to HER2-negative tumors but only at 4 and 24 h; the differences were likely due to non-specific binding of the tracer. The ratios for orthotopic HER2-positive tumors were significantly higher than those for ectopic HER2-negative tumors and melanoma at all time points. However, the differences between HER2-positive and HER2-negative tumors decreased at later time points.ConclusionThese results suggest that [52Mn]Mn-DOTAGA(anhydride)-trastuzumab demonstrates efficient tumor-to-background contrast, emphasize the higher tumor uptake observed in orthotopic tumors, and highlight the influence of tumor environment characteristics on uptake.
ISSN:15322807
DOI:10.3389/pore.2025.1611999