Multimodal Bone Metastasis-associated Epidermal Growth Factor Receptor Imaging in an Orthotopic Rat Model
Laboratory of Molecular Imaging Probes, Department of Radiology; Advanced MRI Center and New England Center for Stroke Research, Department of Radiology
Bioimaging and Biomedical Optics | Neoplasms | Radiology
Purpose: To develop multimodality imaging techniques for measuring epidermal growth factor receptor (EGFR) as a therapy-relevant and metastasis-associated molecular marker in triple-negative mammary adenocarcinoma metastases.
Materials and Methods: An orthotopic bone metastasis EGFR-positive, triple-negative breast cancer (TNBC) model in rats was used for bioluminescence imaging, SPECT/CT, PET/CT, and MRI with quantitative analysis of transcripts (n = 22 rats). Receptor-specific MRI of EGFR expression in vivo was performed by acquiring spin-echo T1-weighted images after sequential administration of a pair of anti-EGFR antigen binding fragments, F(ab')2, conjugated to either horseradish peroxidase or glucose oxidase, which have complementing activities, as well as paramagnetic (gadolinium[III]-mono-5-hydroxytryptamide of 2,2',2''-(10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1 ,4,7-triyl)triacetic acid, or Gd-5HT-DOTAGA) or positron-emitting (gallium 68-5HT-DOTAGA) substrates for MRI and PET/CT imaging, respectively. EGFR expression was confirmed by quantitative reverse transcriptase polymerase chain reaction and immunohistochemical analyses to compare with image findings.
Results: After surgical intraarterial delivery of TNBC cells, rats developed tumors that diverged into either rapidly growing osteolytic or slow-growing nonosteolytic tumors. Both tumor types showed receptor-specific initial MRI signal enhancement (contrast-to-noise ratio) that was three to six times higher than that of normal bone marrow (29.4 vs 4.9; P < .01). Micro PET/CT imaging of EGFR expression demonstrated a high level of heterogeneity with regional uptake of the tracer, which corresponded to region-of-interest MRI signal intensity elevation (121.1 vs 93.3; P < .001). Analysis of metastases with corroboration of imaging results showed high levels of EGFR protein and messenger RNA, or mRNA, expression in the invasive tumor.
Conclusion: Convergence of multimodal molecular receptor imaging enabled comprehensive assessment of EGFR overexpression in an orthotopic model of TNBC metastasis.
Animal Studies, MR-Contrast Agent, Metastases, Molecular Imaging-Cancer, Radionuclide Studies, Skeletal-Appendicular
DOI of Published Version
Bäuerle T, Gupta S, Zheng S, Seyler L, Leporati A, Marosfoi M, Maschauer S, Prante O, Caravan P, Bogdanov A Jr. Multimodal Bone Metastasis-associated Epidermal Growth Factor Receptor Imaging in an Orthotopic Rat Model. Radiol Imaging Cancer. 2021 Jul;3(4):e200069. doi: 10.1148/rycan.2021200069. PMID: 34170199; PMCID: PMC8344354. Link to article on publisher's site
Radiology. Imaging cancer
Bauerle T, Gupta S, Zheng S, Seyler L, Leporati AM, Marosfoi MG, Maschauer S, Prante O, Caravan P, Bogdanov AA. (2021). Multimodal Bone Metastasis-associated Epidermal Growth Factor Receptor Imaging in an Orthotopic Rat Model. Radiology Publications. https://doi.org/10.1148/rycan.2021200069. Retrieved from https://escholarship.umassmed.edu/radiology_pubs/646