Near-infrared fluorescence imaging of HER-2 protein over-expression in tumour cells

Hilger, Ingrid; Leistner, Yvonne; Berndt, Alexander; Fritsche, Christine; Haas, Karl Michael; Kosmehl, Hartwig; Kaiser, Werner A.

doi:10.1007/s00330-004-2257-9

Cited by 69 publications

(56 citation statements)

References 17 publications

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“…Imaging agents derived from antibodies directed against HER2 have demonstrated binding to HER2/neu-overexpressing tumors in preclinical models (24,25). In our study, comparative probe-binding experiments involving the use of breast cancer cell lines with varying degrees of HER2/ neu expression revealed that the described NIR fluorescent HER2 probe can be used to discriminate between HER2-normal and HER2-overexpressing tumors both in vitro and in vivo.…”

Section: Molecular Imaging: Imaging Of Breast Cancer During Her2/neu-mentioning

confidence: 71%

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Human Breast Cancer Tumor Models: Molecular Imaging of Drug Susceptibility and Dosing during HER2/neu-targeted Therapy

Gee¹,

Upadhyay²,

Bergquist³

et al. 2008

Radiology

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Purpose:To use near-infrared (NIR) optical imaging to assess the therapeutic susceptibility and drug dosing of orthotopic human breast cancers implanted in mice treated with molecularly targeted therapy. Materials and Methods:This study was approved by the institutional animal care and use committee. Imaging probes were synthesized by conjugating the human epidermal growth factor receptor type 2 (HER2)-specific antibody trastuzumab with fluorescent dyes. In vitro probe binding was assessed with flow cytometry. HER2-normal and HER2-overexpressing human breast cancer cells were orthotopically implanted in nude mice. Intravital laser scanning fluorescence microscopy was used to evaluate the in vivo association of the probe with the tumor cells. Mice bearing 3-5-mm-diameter tumors were intravenously injected with 0.4 nmol of HER2 probe before or after treatment. A total of 123 mice were used for all in vivo tumor growth and imaging experiments. Tumor fluorescence intensity was assessed, and standard fluorescence values were determined. Statistical significance was determined by performing standard analysis of variance across the imaging cohorts. Results:HER2 probe enabled differentiation between HER2-normal and HER2-overexpressing human breast cancer cells in vitro and in vivo, with binding levels correlating with tumor trastuzumab susceptibility. Serial imaging before and during trastuzumab therapy revealed a significant reduction (P Ͻ .05) in probe binding with treatment and thus provided early evidence of successful HER2 inhibition days before the overall reduction in tumor growth was apparent. Conclusion:NIR imaging with HER2-specific imaging probes enables evaluation of the therapeutic susceptibility of human mammary tumors and of drug dosing during HER2-targeted therapy with trastuzumab. This approach, combined with tomographic imaging techniques, has potential in the clinical setting for determining patient eligibility for and adequate drug dosing in molecularly targeted cancer therapies. RSNA, 2008

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Section: Molecular Imaging: Imaging Of Breast Cancer During Her2/neu-mentioning

confidence: 71%

“…Plasma samples were obtained from the mice (H.B., R.U.) at multiple time points (6,24,48,72, and 96 hours) after probe administration. Whole blood samples were centrifuged in capillary tubes.…”

Section: Determination Of Her2 Probe In Vivo Plasma Half-lifementioning

confidence: 99%

Human Breast Cancer Tumor Models: Molecular Imaging of Drug Susceptibility and Dosing during HER2/neu-targeted Therapy

Gee¹,

Upadhyay²,

Bergquist³

et al. 2008

Radiology

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“…A molecular imaging approach using certain fluorescent probes may vastly improve signal-to-noise ratios by signal amplification [27]. Target-specific fluorescent probes for optical imaging have already been used successfully in animal experiments [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Diffuse optical tomography of the breast: preliminary findings of a new prototype and comparison with magnetic resonance imaging

et al. 2009

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This paper presents an evaluation of a prototype diffuse optical tomography (DOT) system. Seventeen women with 18 breast lesions (10 invasive carcinomas, 2 fibroadenomas, and 6 benign cysts; diameters 13-54 mm) were evaluated with DOT and magnetic resonance imaging (MRI). A substantial fraction of the original 36 recruited patients could not be examined using this prototype due to technical problems. A region of interest (ROI) was drawn at the lesion position as derived from MRI and at the mirror image site in the contralateral healthy breast. ROIs were assessed quantitatively and qualitatively by two observers independently in two separate readings. Intra-and interobserver agreements were calculated using kappa statistics (k) and intraclass correlation coefficients (ICCs). Discriminatory values for presence of malignancy were determined by receiver operating characteristic (ROC) analyses. Intraobserver agreements were excellent (k 0.88 and 0.88; ICC 0.978 and 0.987), interobserver agreements were good to excellent (k 0.77-0.95; ICC 0.96-0.98). Discriminatory values for presence of malignancy were 0.92-0.93 and 0.97-0.99 for quantitative and qualitative ROC analysis, respectively. This DOT system has the potential to discriminate malignant from benign breast tissue in a reproducible qualitative and quantitative manner. Important technical improvements are required before this technique is ready for clinical application.

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“…These probes produced minimal fluorescence outside of the cell, and were activated by sensing the pH change in the lysosome after internalization (Urano et al, 2009). Other optical imaging based applications include imaging SK-BR-3 tumors with Cy5.5-labeled trastuzumab (Hilger et al, 2004), and distinguishing between HER2+ pulmonary metastases and HER2-pulmonary metastases using rhodamine green-conjugated trastuzumab .…”

Section: Wwwintechopencom Targeting Egfr and Her2 For Molecular Imamentioning

confidence: 99%

Targeting EGFR and HER2 for Molecular Imaging of Cancer

Gong¹,

Sampath²,

Kovar³

et al. 2012

Molecular Imaging

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Near-infrared fluorescence imaging of HER-2 protein over-expression in tumour cells

Cited by 69 publications

References 17 publications

Human Breast Cancer Tumor Models: Molecular Imaging of Drug Susceptibility and Dosing during HER2/neu-targeted Therapy

Human Breast Cancer Tumor Models: Molecular Imaging of Drug Susceptibility and Dosing during HER2/neu-targeted Therapy

Diffuse optical tomography of the breast: preliminary findings of a new prototype and comparison with magnetic resonance imaging

Targeting EGFR and HER2 for Molecular Imaging of Cancer

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