Title

Multimodal Bone Metastasis-associated Epidermal Growth Factor Receptor Imaging in an Orthotopic Rat Model

UMMS Affiliation

Laboratory of Molecular Imaging Probes, Department of Radiology; Advanced MRI Center and New England Center for Stroke Research, Department of Radiology

Publication Date

2021-07-01

Document Type

Article

Disciplines

Bioimaging and Biomedical Optics | Neoplasms | Radiology

Abstract

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.

Keywords

Animal Studies, MR-Contrast Agent, Metastases, Molecular Imaging-Cancer, Radionuclide Studies, Skeletal-Appendicular

DOI of Published Version

10.1148/rycan.2021200069

Source

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

Journal/Book/Conference Title

Radiology. Imaging cancer

Related Resources

Link to Article in PubMed

PubMed ID

34170199

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