Development, preclinical safety, formulation, and stability of clinical grade bevacizumab-800CW, a new near infrared fluorescent imaging agent for first in human use

Weele, Eva J. ter; Scheltinga, Anton G.T. Terwisscha van; Linssen, Matthijs D.; Nagengast, Wouter B.; Lindner, Ingo; Jorritsma-Smit, Annelies; Vries, Elisabeth G.E. de; Kosterink, Jos G. W.; Hooge, Marjolijn N. Lub-de

doi:10.1016/j.ejpb.2016.05.008

Cited by 52 publications

(41 citation statements)

References 19 publications

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“…Bevacizumab-IRDye800CW showed high levels of accumulation in human breast cancer-bearing mouse tumors (31), leading to good manufacturing practice (GMP) production of clinical grade bevacizumabIRDye800CW for human use (32). In conjunction with the progress in the development of NIR intraoperative optical imaging systems for clinical applications, we initiated this first-in-human clinical study of clinical grade bevacizumabIRDye800CW in patients with breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Tumor-Specific Uptake of Fluorescent Bevacizumab–IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study

Lamberts

Koch

Jong

et al. 2017

Clinical Cancer Research

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Purpose: To provide proof of principle of safety, breast tumorspecific uptake, and positive tumor margin assessment of the systemically administered near-infrared fluorescent tracer bevacizumab-IRDye800CW targeting VEGF-A in patients with breast cancer.Experimental Design: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab-IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue.

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Section: Introductionmentioning

confidence: 99%

Tumor-Specific Uptake of Fluorescent Bevacizumab–IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study

Lamberts

Koch

Jong

et al. 2017

Clinical Cancer Research

Self Cite

237

191

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“…However, in general, very few details are given on the development and formulation of these tracers (14,24,(33)(34)(35). Several publications have addressed the translation and clinical implications of NIR imaging, but these discuss mostly the camera technology and the design of clinical trials (31,32,36,37), leaving researchers with little guidance on the steps required to progress a tracer from experiment to clinical product.…”

Section: Discussionmentioning

confidence: 99%

“…Labeling procedures were derived from those used for bevacizumab-800CW, as described previously (24). Product yield was determined by size-exclusion high-pressure liquid chromatography.…”

Section: Tracer Conjugation and Purificationmentioning

confidence: 99%

Roadmap for the Development and Clinical Translation of Optical Tracers Cetuximab-800CW and Trastuzumab-800CW

et al. 2019

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Optical molecular imaging using fluorescently labeled monoclonal antibodies is of significant added value in guiding surgical or endoscopic procedures. However, development of tracers for clinical trials is complex, and implementation in the clinic is therefore slow. We present a roadmap for development and translation of monoclonal antibody tracers into a drug product compliant with current good manufacturing processes (cGMPs). Methods: The production process for cetuximab-800CW and trastuzumab-800CW was optimized with regard to dye-to-protein ratio and formulation buffer. Promising formulations were produced under cGMP conditions and advanced to a full-scale stability study. Tracers were analyzed for stability by size-exclusion high-pressure liquid chromatography, pH measurement, osmolality, visual inspection, and sterility, as required by the European Pharmacopeia and cGMP guidelines. Results: Seven formulations were investigated for cetuximab-800CW and 10 for trastuzumab-800CW. On the basis of the formulation study results, we chose 2 formulations per antibody for investigation during the full-scale stability study. These formulations all performed well, showing good compliance with the acceptance criteria set for each product. Conclusion: We designed a roadmap to standardize the development, formulation, and cGMP translation of molecular fluorescent tracers. Using our standardized approach, we developed 2 stable antibody-based tracers for clinical use. The proposed roadmap can be used to efficiently develop a cGMPcompliant formulation and improve the translation of newly developed optical tracers to first-in-human use.

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“…PET imaging using ( 89 Zr)‐bevacizumab has indicated that VEGF‐A is a suitable target for imaging purposes in various tumor types. For the first time, Weele et al286 developed and tested the safety of clinical grade fluorescent‐labeled Bevacizumab‐800CW for non‐invasive NIFR imaging of VEGF‐A in patients with high‐grade dysplasia in Barrett's esophagus. The aim of this project was to validate the formulation, production, quality control, stability, extended characterization, and preclinical safety of a fluorescent imaging agent suitable for first‐in human application (Clinical Trial identifier: NCT02129933).…”

Section: Tumor‐specific Imaging Probes In Clinical Trialsmentioning

confidence: 99%

Interactions Between Tumor Biology and Targeted Nanoplatforms for Imaging Applications

Azizi

Dianat‐Moghadam

Salehi

et al. 2020

Adv Funct Materials

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Although considerable efforts have been conducted to diagnose, improve, and treat cancer in the past few decades, existing therapeutic options are insufficient, as mortality and morbidity rates remain high. Perhaps the best hope for substantial improvement lies in early detection. Recent advances in nanotechnology are expected to increase the current understanding of tumor biology, and will allow nanomaterials to be used for targeting and imaging both in vitro and in vivo experimental models. Owing to their intrinsic physicochemical characteristics, nanostructures (NSs) are valuable tools that have received much attention in nanoimaging. Consequently, rationally designed NSs have been successfully employed in cancer imaging for targeting cancer-specific or cancer-associated molecules and pathways. This review categorizes imaging and targeting approaches according to cancer type, and also highlights some new safe approaches involving membranecoated nanoparticles, tumor cell-derived extracellular vesicles, circulating tumor cells, cell-free DNAs, and cancer stem cells in the hope of developing more precise targeting and multifunctional nanotechnology-based imaging probes in the future.

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Development, preclinical safety, formulation, and stability of clinical grade bevacizumab-800CW, a new near infrared fluorescent imaging agent for first in human use

Cited by 52 publications

References 19 publications

Tumor-Specific Uptake of Fluorescent Bevacizumab–IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study

Tumor-Specific Uptake of Fluorescent Bevacizumab–IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study

Roadmap for the Development and Clinical Translation of Optical Tracers Cetuximab-800CW and Trastuzumab-800CW

Interactions Between Tumor Biology and Targeted Nanoplatforms for Imaging Applications

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