AUTHOR=Ngô Toàn Minh , Vágner Adrienn , Nagy Gábor , Ország Gábor , Nagy Tamás , Szoboszlai Zoltán , Csikos Csaba , Váradi Balázs , Trencsényi György , Tircsó Gyula , Garai Ildikó 

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

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 31 - 2025

YEAR=2025

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2025.1611999

DOI=10.3389/pore.2025.1611999

ISSN=1532-2807

ABSTRACT=Purpose: Positron emission tomography (PET) hybrid imaging targeting HER2 requires antibodies labelled with longer half-life isotopes. With the suitable radiation profile, 52 Mn coupled with DOTAGA as a bifunctional chelator is a potential candidate. In this study, we investigated the tumour HER2 specificity and the temporal biodistribution of the [ 52 Mn]Mn-DOTAGA(anhydride)-trastuzumab in preclinical models.Methods: PET/MRI and PET/CT were performed on SCID mice bearing orthotopic and ectopic HER2-positive and ectopic HER2-negative tumours at 4, 24, 48, 728, and 120 hours post-injection with [ 52 Mn]Mn-DOTAGA(anhydride)-trastuzumab. Melanoma xenografts were included for comparison of specificity.In vivo biodistribution demonstrated strong contrast in HER2-positive tumours, particularly in orthotopic tumours, where uptake was significantly higher than in the blood pool and other organs from 24 hours onwards and consistently higher than in ectopic HER2-positive tumours at all the time points. Significantly higher tumourto-blood and tumour-to-muscle ratios were observed in HER2-positive ectopic tumours compared to HER2negative tumours, but only at 4 and 24 hours; the differences were likely due to non-specific binding of the tracer.In contrast, theThe ratios for orthotopic HER2-positive tumours were significantly higher than those for ectopic HER2-negative tumours and melanoma at all the time points. However, the differences between HER2 -positive and HER2-negative tumours decreased at later time points.These results suggest that [ 52 Mn]Mn-DOTAGA(anhydride)-trastuzumab demonstrates efficient tumour-to-background contrast, emphasise the higher tumour uptake observed in orthotopic tumours, and highlight the influence of tumour environment characteristics on uptake.