Fluorescence-guided Tumor Visualization Using the Tumor Paint BLZ-100

Kittle, David S.; Mamelak, Adam N.; Parrish-Novak, Julia; Hansen, Stacey; Patil, Rameshwar; Gangalum, Pallavi R.; Ljubimova, Julia Y.; Black, Keith L.; Butte, Pramod

doi:10.7759/cureus.210

Cited by 13 publications

(24 citation statements)

References 39 publications

(37 reference statements)

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“…DISCUSSION Tozuleristide, in preclinical studies, has been shown to bind in both primary and metastatic disease to a variety of tumor types including gliomas, sarcomas, and head and neck squamous cell carcinomas. 6,[8][9][10] Here we show for the first time that tozuleristide binds breast carcinomas in a clinical study. Signal for invasive carcinoma appeared bright and focal in ex vivo imaging of sectioned fresh breast tissue.…”

Section: Arch Pathol Lab Med-vol 143 September 2019mentioning

confidence: 60%

Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide

Dintzis

Hansen

Harrington

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Resection of breast carcinoma with adequate margins reduces the risk of local recurrence and reoperation. Tozuleristide (BLZ-100) is an investigational peptide-fluorophore agent that may aid in intraoperative tumor detection and margin assessment. In this study, fluorescence imaging was conducted ex vivo on gross breast pathology specimens. Objectives.— To determine the potential of tozuleristide to detect breast carcinoma in fresh pathology specimens and the feasibility of fluorescence-guided intraoperative pathology assessment of surgical margins. Design.— Twenty-three patients received an intravenous bolus dose of 6 or 12 mg of tozuleristide at least 1 hour before surgery. Fifteen lumpectomy and 12 mastectomy specimens were evaluated for fluorescence by the site's clinical pathology staff using the SIRIS, an investigational near-infrared imaging device. The breast tissue was then processed per usual procedures. Fluorescent patterns were correlated with the corresponding hematoxylin-eosin–stained sections. Clinical pathology reports were used to correlate fluorescent signal to grade, histotype, prognostic marker status, and margin measurements. Results.— Tozuleristide fluorescence was readily observed in invasive and in situ breast carcinoma specimens. Most invasive carcinomas were bright and focal, whereas in situ lesions demonstrated a less intense, more diffuse pattern. Tozuleristide was detected in ductal and lobular carcinomas with a similar fluorescent pattern. Fluorescence was detected in high- and low-grade lesions, and molecular marker/hormone receptor status did not affect signal. Fluorescence could be used to identify the relationship of carcinoma to margins intraoperatively. Conclusions.— Tumor targeting with tozuleristide allowed visual real-time distinction between pathologically confirmed breast carcinoma and normal tissue.

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Section: Arch Pathol Lab Med-vol 143 September 2019mentioning

confidence: 60%

Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide

Dintzis

Hansen

Harrington

et al. 2018

Archives of Pathology &Amp; Laboratory Medicine

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“…19,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] The long-term interest in the intraoperative NIR fluorescence visualization is driven by the development of new agents capable of improved delineation of brain tumor margins. Examples of dyes include various derivatives of NIR fluorescent dye currently undergoing preclinical or clinical evaluations, such as BLZ-100, a chlorotoxin-ICG conjugate; 36,37 CLR1502, an alkylphopholine derivative of a cyanine dye; 40,41 anti-EGFR antibody fragments conjugated to IRDye 800 CW; 42,43 and others. 44 We believe that the ability to simultaneously visualize the surgical field and contrast agent within the augmented microscope will enable broad implementation of image guidance in surgeries.…”

Section: Discussionmentioning

confidence: 99%

Augmented microscopy: real-time overlay of bright-field and near-infrared fluorescence images

et al. 2015

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Abstract. Intraoperative applications of near-infrared (NIR) fluorescent contrast agents can be aided by instrumentation capable of merging the view of surgical field with that of NIR fluorescence. We demonstrate augmented microscopy, an intraoperative imaging technique in which bright-field (real) and electronically processed NIR fluorescence (synthetic) images are merged within the optical path of a stereomicroscope. Under luminance of 100,000 lx, representing typical illumination of the surgical field, the augmented microscope detects 189 nM concentration of indocyanine green and produces a composite of the real and synthetic images within the eyepiece of the microscope at 20 fps. Augmentation described here can be implemented as an add-on module to visualize NIR contrast agents, laser beams, or various types of electronic data within the surgical microscopes commonly used in neurosurgical, cerebrovascular, otolaryngological, and ophthalmic procedures.

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“…23 Some of these studies have used resolution targets to identify CTF graphs, 21 whereas others use them for a more qualitative assessment. 22 In a recently published comprehensive multiuse phantom, 16 a resolution target embedded in a turbid matrix was shown to be unusable for determining CTF during surface imaging. Alternate approaches for evaluating NIRF system resolution have included the use of small parallel fluorophores and crossed tubes.…”

Section: D1 Spatial Resolutionmentioning

confidence: 99%

“…Prior studies on medical imaging, [8][9][10] NIRF, [1][2][3][4][11][12][13][14][15][16][17][18] and other optical modalities (e.g., hyperspectral) 19,20 identify key characteristics relevant for en-face imaging. Several key commonly cited metrics are spatial resolution, 15,[21][22][23][24][25][26][27][28][29] sensitivity/ detectability, 1,7,[11][12][13][15][16][17][21][22][23][24][25][26][27][28][29][30][31] linearity, 11,13,17,32,3...…”

Section: Introductionmentioning

confidence: 99%

Performance test methods for near‐infrared fluorescence imaging

et al. 2020

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Purpose: Near-infrared fluorescence (NIRF) imaging using exogenous contrast has gained much attention as a technique for enhancing visualization of vasculature using untargeted agents, as well as for the detection and localization of cancer with targeted agents. In order to address the emerging need for standardization of NIRF imaging technologies, it is necessary to identify the best practices suitable for objective, quantitative testing of key image quality characteristics. Toward the development of a battery of test methods that are rigorous yet applicable to a wide variety of devices, we have evaluated techniques for phantom design, measurement, and calculation of specific performance metrics. Methods: Using a NIRF imaging system for indocyanine green imaging, providing excitation at 780 nm and detection above 830 nm, we explored methods to evaluate uniformity, field of view, spectral crosstalk, spatial resolution, depth of field, sensitivity, linearity, and penetration depth. These measurements were performed using fluorophore-doped multiwell plate and high turbidity planar phantoms, as well as a 3D-printed multichannel phantom and a USAF 1951 resolution target. Results and Conclusions: Based on a wide range of approaches described in medical and fluorescence imaging literature, we have developed and demonstrated a cohesive battery of test methods for evaluation of fluorescence image quality in wide-field imagers. We also propose a number of key metrics that can facilitate direct, quantitative comparison of device performance. These methods have the potential to facilitate more uniform evaluation and inter-comparison of clinical and preclinical imaging systems than is typically achieved, with the long-term goal of establishing international standards for fluorescence image quality assessment.

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Fluorescence-guided Tumor Visualization Using the Tumor Paint BLZ-100

Cited by 13 publications

References 39 publications

Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide

Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide

Augmented microscopy: real-time overlay of bright-field and near-infrared fluorescence images

Performance test methods for near‐infrared fluorescence imaging

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