Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

Boer, Esther de; Samuel, Sharon; French, David N.; Warram, Jason M.; Schoeb, Trenton R.; Rosenthal, Eben L.; Zinn, Kurt R.

doi:10.1007/s11307-015-0892-y

Cited by 11 publications

(13 citation statements)

References 16 publications

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“…Although we did not evaluate ZIKV-specific antibody levels in lymph nodes in the present study, studies with monoclonal antibodies have shown substantial variation in antibody biodistribution to different tissues, including lymph node and brain, as compared with peripheral blood (de Boer et al, 2016; Tichauer et al, 2014; Wang et al, 2008). In the CSF, it is likely that the absence of ZIKV-specific antibodies contributed to viral persistence in that compartment.…”

Section: Discussionmentioning

confidence: 95%

Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys

Aïd

Abbink

Larocca

et al. 2017

Cell

197

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SUMMARY Zika virus (ZIKV) is associated with severe neuropathology in neonates as well as Guillain-Barre syndrome and other neurologic disorders in adults. Prolonged viral shedding has been reported in semen, suggesting the presence of anatomic viral reservoirs. Here we show that ZIKV can persist in cerebrospinal fluid (CSF) and lymph nodes (LN) of infected rhesus monkeys for weeks after virus has been cleared from peripheral blood, urine, and mucosal secretions. ZIKV-specific neutralizing antibodies correlated with rapid clearance of virus in peripheral blood but remained undetectable in CSF for the duration of the study. Viral persistence in both CSF and LN correlated with upregulation of mechanistic target of rapamycin (mTOR), proinflammatory, and anti-apoptotic signaling pathways, as well as downregulation of extracellular matrix and cell signaling pathways. These data raise the possibility that persistent or occult neurologic and lymphoid disease may occur following clearance of peripheral virus in ZIKV-infected individuals.

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Section: Discussionmentioning

confidence: 95%

Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys

Aïd

Abbink

Larocca

et al. 2017

Cell

197

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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%

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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“…In fact, lymph node and cancer physiology, rather than cancer‐specific binding, can dominate the pharmacokinetics of imaging agents in terms of their accumulation and retention in lymph nodes for both systemically and locally delivered methods. To account for this, a growing number of groups have been using so‐called paired‐agent or ratiometric imaging methods.…”

Section: Molecular Targeted Imaging Agent Methodsmentioning

confidence: 99%

“…A common concern regarding the clinical translation of paired‐agent imaging protocols is that it is already very onerous to approve 1 imaging agent for clinical use, let alone 2. With respect to this, there are recent unpublished results in our lab suggesting that indocyanine green—which is already approved for clinical use and has now been used in multiple lymph node mapping applications—can act as an ideal control imaging agent when coadministered with IRDye700DX‐labeled antibodies, such as the GMP‐produced, and ready‐for‐human‐use, anti‐EGFR agent developed by de Boer et al…”

Section: Paired‐agent and Ratiometric Methodsmentioning

confidence: 99%

Noninvasive detection of cancer spread to lymph nodes: A review of molecular imaging principles and protocols

Torres

Tichauer

2018

Journal of Surgical Oncology

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Identification of cancer spread to tumor-draining lymph nodes offers critical information for guiding treatment in many cancer types. Current clinical methods of nodal staging are invasive and can have substantial negative side effects. Molecular imaging protocols have long been proposed as a less invasive means of nodal staging, having the potential to enable highly sensitive and specific evaluations. This review article summarizes the current status and future perspectives for molecular targeted nodal staging.

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Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

Abstract: Both IR700 and intact cetuximab-IR700 biodistributions were consistent with known epidermal growth factor receptor (EGFR) expression, and changes between 2 and 14 days were consistent with rapid metabolism and excretion of the cetuximab-IR700.

Cited by 11 publications

References 16 publications

Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys

Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys

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

Noninvasive detection of cancer spread to lymph nodes: A review of molecular imaging principles and protocols

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