A Novel Fluorescent Imaging Agent for Diffuse Optical Tomography of the Breast: First Clinical Experience in Patients

Ven, Stephanie M. W. Y. van de; Wiethoff, Andrea J.; Nielsen, Tim; Brendel, Bernhard; Voort, Marjolein van der; Nachabé, Rami; Mark, M.; Beek, Michiel van; Bakker, Leon; Fels, Lueder; Elias, Sjoerd G.; Luijten, Peter R.; Mali, Willem P.Th.M.

doi:10.1007/s11307-009-0269-1

Cited by 65 publications

(53 citation statements)

References 22 publications

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“…Moreover, several optical contrast agents are available, which may improve contrast and sensitivity (31,32). Furthermore, DOS can be combined with other imaging modalities, such as ultrasound, for improved tumor localization accuracy (11).…”

Section: Discussionmentioning

confidence: 99%

Optical Mammography Using Diffuse Optical Spectroscopy for Monitoring Tumor Response to Neoadjuvant Chemotherapy in Women with Locally Advanced Breast Cancer

Schaafsma

Giessen

Charehbili

et al. 2015

Clinical Cancer Research

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Purpose: Diffuse optical spectroscopy (DOS) has the potential to enable monitoring of tumor response during chemotherapy, particularly in the early stages of treatment. This study aims to assess feasibility of DOS for monitoring treatment response in HER2-negative breast cancer patients receiving neoadjuvant chemotherapy (NAC) and compare DOS with tumor response assessment by MRI.Experimental Design: Patients received NAC in six cycles of 3 weeks. In addition to standard treatment monitoring by dynamic contrast enhanced MRI (DCE-MRI), DOS scans were acquired after the first, third, and last cycle of chemotherapy. The primary goal was to assess feasibility of DOS for early assessment of tumor response. The predictive value of DOS and DCE-MRI compared with pathologic response was assessed.Results: Of the 22 patients, 18 patients had a partial or complete tumor response at pathologic examination, whereas 4 patients were nonresponders. As early as after the first chemotherapy cycle, a significant difference between responders and nonresponders was found using DOS (HbO 2 86% AE 25 vs. 136% AE 25, P ¼ 0.023). The differences between responders and nonresponders continued during treatment (halfway treatment, HbO 2 68% AE 22 vs. 110% AE 10, P ¼ 0.010). Using DCE-MRI, a difference between responders and nonresponders was found halfway treatment (P ¼ 0.005) using tumor volume measurement calculations.Conclusions: DOS allows for tumor response assessment and is able to differentiate between responders and nonresponders after the first chemotherapy cycle and halfway treatment. In this study, DOS was equally effective in predicting tumor response halfway treatment compared with DCE-MRI. Therefore, DOS may be used as a novel imaging modality for (early) treatment monitoring of NAC.

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Section: Discussionmentioning

confidence: 99%

Optical Mammography Using Diffuse Optical Spectroscopy for Monitoring Tumor Response to Neoadjuvant Chemotherapy in Women with Locally Advanced Breast Cancer

Schaafsma

Giessen

Charehbili

et al. 2015

Clinical Cancer Research

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“…As a result, visualizing submillimeter spatial variations in binding potential within a deep-seated tumor will likely be infeasible. Despite this limitation, quantifying the average available receptor density in tumor masses is achievable in research animals, and the recent history of FMT studies in the human breast (24,44) suggests that translating the technology to clinical imaging is feasible for tissue organs accessible by FMT imaging geometries.…”

Section: Discussionmentioning

confidence: 99%

Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo

Davis

Samkoe²,

Tichauer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model to estimate the density of receptors available for binding in the tissue. Applying this approach to mice with deep-seated gliomas that overexpress the EGF receptor produced an estimate of available receptor density of 2.3 ± 0.5 nM (n = 5), consistent with values estimated in comparative invasive imaging and ex vivo studies.

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“…When used for studying breast tissue, diffuse optical imaging is often referred to as optical mammography. This technique is currently being tested in early clinical trials (37). Confocal laser endomicroscopy allows in vivo imaging of the mucosal layer during gastrointestinal endoscopy.…”

Section: Discussionmentioning

confidence: 99%

Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies

Scheltinga¹,

Dam²,

Nagengast³

et al. 2011

J Nucl Med

177

141

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Fluorescence imaging is currently attracting much interest as a method for intraoperative tumor detection, but most current tracers lack tumor specificity. Therefore, this technique can be further improved by tumor-specific detection. With tumortargeted antibodies bound to a radioactive label, tumor-specific SPECT or PET is feasible in the clinical setting. The aim of the present study was to apply antibody-based tumor detection to intraoperative optical imaging, using preclinical in vivo mouse models. Methods: Anti-vascular endothelial growth factor (VEGF) antibody bevacizumab and anti-human epidermal growth factor receptor (HER) 2 antibody trastuzumab were labeled with the near-infrared (NIR) fluorescence dye IRDye 800CW. Tumor uptake of the fluorescent tracers and their 89 Zr-labeled radioactive counterparts for PET was determined in human xenograft-bearing athymic mice during 1 wk after tracer injection, followed by ex vivo biodistribution and pathologic examination. Intraoperative imaging of fluorescent VEGF-or HER2-positive tumor lesions was performed in subcutaneous tumors and in intraperitoneal dissemination tumor models. Results: Tumorto-background ratios, with fluorescent imaging, were 1.93 6 0.40 for bevacizumab and 2.92 6 0.29 for trastuzumab on day 6 after tracer injection. Real-time intraoperative imaging detected tumor lesions at even the submillimeter level in intraperitoneal dissemination tumor models. These results were supported by standard histology, immunohistochemistry, and fluorescence microscopy analyses. Conclusion: NIR fluorescence-labeled antibodies targeting VEGF or HER2 can be used for highly specific and sensitive detection of tumor lesions in vivo. These preclinical findings encourage future clinical studies with NIR fluorescence-labeled tumor-specific antibodies for intraoperative-guided surgery in cancer patients.

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A Novel Fluorescent Imaging Agent for Diffuse Optical Tomography of the Breast: First Clinical Experience in Patients

Cited by 65 publications

References 22 publications

Optical Mammography Using Diffuse Optical Spectroscopy for Monitoring Tumor Response to Neoadjuvant Chemotherapy in Women with Locally Advanced Breast Cancer

Optical Mammography Using Diffuse Optical Spectroscopy for Monitoring Tumor Response to Neoadjuvant Chemotherapy in Women with Locally Advanced Breast Cancer

Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo

Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies

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