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Monoclonal Antibodies for Targeted Fluorescence-Guided Surgery: A Review of Applicability across Multiple Solid Tumors

Stefano Giuliani
Irene Paraboschi
Angus McNair
Myles Smith
Kenneth S. Rankin
Daniel S. Elson
Vinidh Paleri
Daniel Leff
Graeme Stasiuk
13 and
John Anderson
2 on behalf of the Precision Surgery Group at the NIHR Oncology Translational Research Collaboration
Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London W1W 7TY, UK
Cancer Section, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK
Department of Specialist Neonatal and Paediatric Surgery, Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK
Department of Biomedical and Clinical Science, University of Milano, 20157 Milan, Italy
National Institute for Health Research Bristol Biomedical Research Centre, Bristol Centre for Surgical Research, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK
Department of Gastrointestinal Surgery, North Bristol NHS Trust, Bristol BS10 5NB, UK
The Sarcoma, Melanoma and Rare Tumours Unit, The Royal Marsden Hospital, Institute Cancer of Research, London SW3 6JJ, UK
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
North of England Bone and Soft Tissue Tumour Service, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK
Hamlyn Centre for Robotic Surgery, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
Head and Neck Unit, The Royal Marsden Hospitals, London SW3 6JJ, UK
Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, King’s College London, St Thomas’ Hospital, London SE1 7EH, UK
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2024, 16(5), 1045;
Submission received: 2 February 2024 / Revised: 25 February 2024 / Accepted: 28 February 2024 / Published: 4 March 2024
(This article belongs to the Special Issue New Findings in Targeting Cancer Proteins)



Simple Summary

Due to their specificity, monoclonal antibodies have significantly impacted cancer patients’ care, becoming one of the fastest-growing classes of new drugs approved for the treatment of solid tumors. Targeted fluorescence-guided surgery is a novel technology to better visualize tumor residuals intraoperatively. It consists of a fluorescent molecular probe, that, once injected, lights up the neoplastic cells during the surgical resection. In this regard, the development of an off-the-shelf large-scale production of clinically approved, fluorescently labeled monoclonal antibodies for targeted fluorescence-guided surgery is becoming an urgent need for oncological surgeons working in this field. Our paper aims to present the current evidence on the clinical use of monoclonal antibodies targeting solid adult and pediatric cancers. Particularly, we aim to define the utility, indications, doses, and timing of administration of the most promising monoclonal antibodies to be used for targeted fluorescence-guided surgery in oncology patients. We will also define the top three monoclonal antibodies that could be used for targeted fluorescence-guided surgery in different solid cancers, to set the basis of a bank of monoclonal antibodies that can be used to deliver highly individualized and personalized surgical approaches.


This study aims to review the status of the clinical use of monoclonal antibodies (mAbs) that have completed or are in ongoing clinical trials for targeted fluorescence-guided surgery (T-FGS) for the intraoperative identification of the tumor margins of extra-hematological solid tumors. For each of them, the targeted antigen, the mAb generic/commercial name and format, and clinical indications are presented, together with utility, doses, and the timing of administration. Based on the current scientific evidence in humans, the top three mAbs that could be prepared in a GMP-compliant bank ready to be delivered for surgical purposes are proposed to speed up the translation to the operating room and produce a few readily available “off-the-shelf” injectable fluorescent probes for safer and more effective solid tumor resection.

1. Introduction

Due to their target specificity and immunomodulatory properties, monoclonal antibodies (mAbs) have significantly impacted cancer patients’ care, becoming one of the fastest growing groups of new drugs approved for the cure of solid tumors [1]. mAbs have been effectively used to elicit long-lasting effector responses against solid malignancies by exploiting their unique capability of directly killing cancer cells while simultaneously activating the host immune system [1]. As a form of radioimmunotherapy, mAbs have also been adopted to selectively deliver high doses of radiation to tumor cells while also reducing the exposure of the surrounding healthy tissues, thus enhancing the efficacy of standard radiotherapy while minimizing its side effects [2].
Recently, fluorescently labeled mAbs have been used in the operating theatre to help surgeons better visualize and remove solid tumors in real time. This has been a revolution in the field of targeted fluorescence-guided surgery (T-FGS). Even if the adoption of fluorescently labeled mAbs in surgical oncology is still in its infancy, its applications are growing fast, with real potential to revolutionize the surgical field [3,4,5,6,7,8,9,10]. In this regard, the development of an “off-the-shelf” large-scale production of clinically approved fluorescently labeled mAbs is becoming an urgent need for oncological surgeons working in this surgical field.
This review paper focuses on presenting clinical evidence on the use of mAbs as the method to deliver T-FGS in adult and pediatric solid cancers. We will not consider other targeted forms of T-FGS, which are not mAb-driven, and we will exclude solid hematological cancers (e.g., lymphomas).
Particularly, we aim to define the utility, indications, doses, and timing of administration of the most promising mAbs to be used for T-FGS in oncology patients. Then, we will propose the top three mAbs that could be prepared in a GMP-compliant bank ready to be delivered for intraoperative tumor visualization.

2. Fluorescence-Guided Surgery (FGS): Non-Specific and Monoclonal Antibody (mAb)-Targeted

FGS is an emerging imaging tool that permits surgeons to identify healthy and pathological tissues, in real time, by intravenously delivering non-specific fluorophores (e.g., indocyanine green (ICG), 5-aminolevulinic acid, or fluorescein sodium) or fluorescently labeled molecules with a particular tissue or tumor tropism (e.g., mAbs). Depending on their route of administration, systemically administered non-specific fluorescent dyes can be used to help surgeons identify blood, bile, and lymphatic vessels during surgery, bridging the gap existing between preoperative anatomical imaging and patient-specific surgical findings [11,12].
In the surgical oncology field, non-specific dyes could be employed to distinguish neoplastic lesions from the surrounding normal tissues, by exploiting the enhanced permeability and retention (EPR) effects caused by the leaky nature of tumor vessels and the compromised lymphatic drainage [3,4,5,6,7,8,9]. Unfortunately, non-specific dyes are often unable to cause tumors from a diverse range of cancer types to fluoresce effectively as the EPR effect is not homogenous or reliable.
Besides non-specific fluorescent dyes, fluorophores have been conjugated to mAbs to deliver T-FGS, thus enhancing the intraoperative visualization of cancer at the tumor margins, loco-regional lymph nodes, and occult disease with high resolution and deep tissue penetration. By binding to a specific site of the tumor antigen (i.e., epitope), fluorescently labeled mAbs can be administered a few days before surgery, and then visualized using new-generation near-infrared (NIR) camera systems for endoscopic and open-field procedures [3,4,5,6,7,8,9].
Building on the widespread use of non-specific FGS and ICG, biomedical device companies have developed several NIR fluorescence platforms, which can be used to detect mAb-based FGS [3,4,5,8]. Briefly, the fluorophore-conjugated mAb needs to be excited at a specific wavelength to produce an invisible light, which will be collected at a set wavelength range to be transformed into an image. For surgical indications, mAbs have been conjugated to NIR dyes (e.g., IRDye800CW; wavelengths: 650–900 nm), which provide low absorption in healthy tissue, high tumor-to-background-ratio (TBR) and tissue penetration, with low interference from intrinsic fluorescence, especially when compared to the visible light spectrum (wavelengths: 400–600 nm). By doing so, the non-specific tissue background can be minimized while the tumor cells can be illuminated in real-time helping surgeons with better visualization [3,4,5,6,7,8,9].

3. Monoclonal Antibodies (mAbs) Clinically Approved for the Treatment of Extra-Hematological Solid Malignancies under Evaluation in Clinical Trials for T-FGS Purposes

In this section, mAbs clinically approved for the treatment of extra-hematological solid malignancies are presented. For each of them, we will report the antigen targeted, mAb generic/commercial name and format, and clinical indication (Table 1). Then, we will present completed or ongoing human clinical trials using mAbs for T-FGS with a focus on indications, doses, the timing of administration, and safety profile (Table 2).
  • mAbs targeting the epidermal growth factor receptor (EGFR)
The EGFR (c-ErbB1, HER1) is a 170 kDa transmembrane glycoprotein belonging to the epidermal growth factor receptor (ErbB) family [13,14].
The members of this family of type I receptor tyrosine kinases, which also include c-ErbB2 (HER2, neu in rodents), c-ErbB3 (HER3), and c-ErbB4 (HER4), share similarities in their structure (i.e., an extracellular domain, a lipophilic transmembrane region, an intracellular domain containing tyrosine kinase, and a carboxy-terminal region) and function [13,14].
Despite being a monomer in its inactive form, when it is bounded by its ligands (e.g., EGF, TNFα), EGFR forms homodimers or heterodimers with another member of its family of receptors and activates its intracellular tyrosine kinase region. This results in its autophosphorylation and in the initiation of a cascade of intracellular events, which regulate tumor cell differentiation, proliferation, angiogenesis, and migration [13,14].
Several alterations in EGFR are associated with the growth and spread of different solid tumors in humans. Hence, this surface antigen has been extensively studied over time together with the effects of anti-EGFR mAbs on EGFR-positive tumors [13,14].
Since anti-EGFR mAbs are bound to EGFR with a higher affinity compared with its ligands, they inhibit the subsequent activation of the tyrosine kinase-mediated cascade of intracellular events [13,14].
Cetuximab (Erbitux) is a recombinant human/mouse chimeric IgG1 mAb that binds to the extracellular domain of the human EGFR and, therefore, competitively inhibits EGF and other ligand binding. The inhibition of cell proliferation, the induction of apoptosis, and reduced matrix metalloproteinase and vascular endothelial growth factor (VEGF) production are all results of the binding of Cetuximab to its receptor. This mAb is currently approved for the treatment of recurrent squamous-cell carcinoma of the head and neck, K-Ras wild-type EGFR-expressing colorectal cancer, and BRAF V600E mutation-positive metastatic colorectal cancer. The safety and tumor specificity of Cetuximab-IRDye800CW as a surgical navigation tool have been successfully demonstrated in multiple in vitro and in vivo models of human cancers, showing limited toxicity. Moreover, several early-phase clinical trials are in progress to test the safety, efficacy, reactions, best dosage, formulation method, and efficacy of its administration. Table 2 lists the solid tumors currently under investigation for T-FGS applications of Cetuximab-IRDye800CW, including esophageal cancer ( NCT04161560), head and neck cancer ( NCT03134846, NCT01987375), pancreatic adenocarcinoma ( NCT02736578), brain neoplasm ( NCT02855086), rectal cancer ( NCT04638036), and penile cancer ( NCT05376202).
In 2015, Rosenthal et al. [15] published a dose escalation study of Cetuximab- IRDye800CW enrolling 12 patients undergoing surgery for squamous-cell carcinoma of the head and neck. This report represents a milestone in the application of tumor biology-based FGS because it proved for the first time that commercially available mAb could be labeled with fluorophores and safely administered to patients in order to identify in real-time solid tumors with sharp demarcation and deep resolution. According to the study design, the escalating doses were based on the therapeutic dose of Cetuximab (250 mg/m2): 2.5 mg/m2, 25.0 mg/m2, and 62.5 mg/m2, corresponding to the 1%, 10%, and 25% of the therapeutic dose. Wide-field NIR imaging was performed after infusion on days 0, 1, and on the day of surgical resection. While no severe side effects were reported, an average TBR of 5.2 in the highest dose range helped successfully differentiate the tumor from the surrounding healthy tissue during surgery.
Three years later, Miller et al. [16] used Cetuximab conjugated with IRDye800CW for intraoperative imaging during glioblastoma resection. Two doses (50 and 100 mg) were administered 2–5 days before surgery to identify the optimal TBR. It is worth noting that a 100 mg loading dose of unlabeled Cetuximab was infused before the fluorescent agent to differentiate potential adverse reactions and to saturate tissues highly expressing EGFR (e.g., liver). Interestingly, the administered dose correlated with the TBR (mean: 3.6 vs. 4.3) and the smallest detectable tumor volume (70 mg vs. 10 mg), and so did the specificity (66.3% vs. 69.8%) and sensitivity for viable tumor tissue (73.0% vs. 98.2%). With the limitation of a small number of patients included, this study represents a pivotal proof-of-principle of the feasibility, safety, and capacity of mAb-based imaging to traverse the blood–brain barrier for contrast-enhancing glioblastomas.
Panitumumab (Vectibix) is a fully human IgG2 anti-EGFR mAb, currently used for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer.
Panitumumab-IRDye800CW has been employed for FGS in patients with head and neck cancer ( NCT04511078, NCT03405142, NCT02415881, NCT03733210), lung cancer ( NCT03582124), brain tumor ( NCT04085887, NCT03510208), and pancreatic adenocarcinoma ( NCT03384238).
In 2018, Gao et al. [17] published the results of a Phase I clinical trial enrolling 15 patients with biopsy-confirmed head and neck squamous-cell carcinoma undergoing standard surgery.
One to five days before surgery, 100 mg of unlabeled Panitumumab were administered to patients as a loading dose to limit background. In case of no drug reaction, a dose of 0.06 mg/kg Panitumumab-IRDye800CW (1/100 of one therapeutic dose), 0.5 mg/kg (1/12 of one therapeutic dose), or 1 mg/kg (1/6 of one therapeutic dose) was infused. The results of this study together with those of similar mAb-based imaging studies suggested that Panitumumab-IRDye800CW has toxicity and pharmacodynamic profiles like the unconjugated mAb, and that its safety profile can be exploited to design safe and effective fluorescent imaging probes at doses up to 25% of the therapeutic one.
Moreover, by histologically correlating the tumor location with fluorescence intensities, the authors reported a high TBR, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the tested optical imaging agent at both doses (0.5 mg/kg: 9.96 ± 1.30; 80.0%; 94.8%, 42.7%, and 96.5%, respectively; 1 mg/kg: 8.85 ± 1.26; 83.7%; 72.1%; 20.6%, and 99.5%; respectively) that significantly aided in the real-time detection of surgical resection margins of head and neck squamous-cell carcinomas.
More recently, Zhou et al. [18] investigated the use of Panitumumab-IRDye800CW, administered at subtherapeutic doses, as a safe and effective imaging agent for high-grade gliomas. According to the study design, 11 patients affected by contrast-enhancing high-grade gliomas were administered Panitumumab-IRDye800CW at two doses (low: 50 mg; high: 100 mg) 1–5 days before surgery. The authors concluded that Panitumumab-IRDye800CW was safe at both doses and provided excellent intraoperative contrast in a dose-dependent way (smallest detectable tissue weights: 3 mg vs. 66 mm), with no difference in the observed NIR fluorescence in tumor tissue resected among the three imaging windows. Although viable tumor tissue could be visualized with PPV and NPV above 85% at both doses, the highest dose provided a superior AUC compared to 50 mg (0.90 vs. 0.85), which was thus more appropriate for real-time surgical imaging.
  • mAbs targeting the vascular endothelial growth factor (VEGF)
Angiogenesis is a complex phenomenon, involving several series of events, including the outgrowth of post-capillary vessels from pre-existing venules, vasodilation, increased permeability, and the migration of endothelial progenitor cells. Besides the tightly regulated process occurring during the normal growth of an organism and the tissue repair occurring during wound healing, solid malignancies also upregulate angiogenetic processes to induce nutrient delivery and tumor growth [19,20].
In this regard, the protein family of VEGF has been demonstrated to play major roles in physiological and pathological angiogenesis by providing signaling pathways and cascades of events crucial for endothelial cell division and migration. The VEGF family consists of six secreted proteins including VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placenta-induced growth factor (PDGF), characterized by eight conserved cysteines and functions as a homodimer structure. These ligands bind to three different, but structurally related, VEGF-receptor (VEGFR) tyrosine kinases, essential for hematopoietic, vascular endothelial, and lymphatic endothelial cell development [19,20].
Bevacizumab (Avastin) is a recombinant humanized anti-VEGF IgG1 mAb that contains human framework regions and murine complementarity-determining regions. Bevacizumab binds VEGF and interferes with the interaction of VEGF with its receptors (Flt-1 and KDR) on the surface of endothelial cells, preventing angiogenetic events.
It has been approved for patients affected with metastatic colorectal cancers, unresectable, locally advanced, recurrent, or metastatic non-squamous non-small-cell lung cancers, recurrent glioblastomas, metastatic renal-cell carcinomas, persistent, recurrent, or metastatic cervical cancers, epithelial ovarian, fallopian tube, or primary peritoneal cancers, and unresectable or metastatic hepatocellular carcinoma.
Different treatment protocols have been described according to the different histological subtypes, with specific guidelines and recommendations for drug infusion, dosage calculations, ortive treatment, the monitoring of vital parameters, and criteria for dose changes.
Bevacizumab-IRDye800CW has been leveraged for delivering precision surgery in several clinical trials enrolling patients with adenomatous polyposis coli ( NCT02113202), rectal cancer ( NCT01972373), breast cancer ( NCT01508572), soft-tissue sarcoma ( NCT03913806), Barrett esophagus ( NCT03877601), esophageal cancer ( NCT02129933, NCT03558724), hilar cholangiocarcinoma ( NCT03620292), inverted papilloma ( NCT03925285), pancreatic cancer ( NCT02743975), and pituitary tumor ( NCT04212793).
In 2016, Harlaar et al. [21] ran a single-center feasibility study to prove the safety of molecular FGS using Bevacizumab-IRDye800CW in seven patients with colorectal peritoneal metastases scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. No serious side effects related to its administration were reported in any of the patients enrolled receiving 4.5 mg (1 mg/mL) of the NIR fluorescent tracer 2 days before surgery. Of interest, fluorescence was seen intraoperatively in all patients, and in two patients, additional tumor tissues that were initially missed by the surgeons were detected by FGS itself. Although molecular FGS was associated with more false-positive results than expected initially (in fact, tumor tissue was detected in 27 of 51 fluorescent areas, 53%), no residual disease was found in the absence of fluorescence.
A year later, Lamberts et al. [22] published a proof-of-principle study describing the safety of 4.5 mg Bevacizumab-IRDye800CW in 21 patients affected with primary invasive breast cancer eligible for primary surgery. Interestingly, none had side effects, and even if in situ intraoperative tumor margin detection was not possible (due to the microdose of the tracer administered) the ex vivo imaging proved to correlate well with VEGF-A quantification and microscopic analyses of the tumor site of targeting. Further studies adopting higher tracer doses, albeit still well below the therapeutic dosing scheme of Bevacizumab, were therefore warranted for intraoperative in situ imaging purposes.
More recently, in 2020, J. de Jongh et al. [23] demonstrated the potential of back-table FGS for the evaluation in the surgical theatre of the margin of locally advanced rectal cancers following the administration of 4.5 mg of Bevacizumab-800CW 2–3 days before surgery. The technique itself proved to be safe and feasible and showed huge potential for guiding intraoperative decision-making with high sensitivity.
In the same year, Tjalma et al. [24] evaluated the role of quantitative fluorescence endoscopy targeting VEGF A to detect residual tumors after neoadjuvant chemoradiotherapy in a first-in-human pilot by enrolling 25 patients with locally advanced rectal cancer who received 4.5 mg of Bevacizumab-800CW intravenously 2–3 days prior to endoscopy. Their results demonstrated that this image-guided technique aided clinical response assessment in the patients by showing significantly higher fluorescent signals in tumors compared with healthy rectal tissue and fibrosis and by improving the prediction of final pathology results in 16% of patients compared with standard MRI and white-light endoscopy. Further studies involving more patients are warranted to realize this strategy.
  • mAbs targeting carbonic anhydrase IX (CAIX)
Carbonic anhydrase IX (CAIX) is a zinc metalloprotein enzyme. CAIX belongs to the carbonic anhydrase family. Under conditions associated with low pH, CAIX is triggered by the hypoxia-inducible factor 1-α (HIF1-α) and is highly upregulated in environments characterized by a low pressure of oxygen. By catalyzing the interconversion of CO2 and HCO3 to maintain intracellular pH homeostasis, the overexpression of CAIX contributes to cancer cell survival. Not only does CAIX modulate the microenvironment, but it also has a critical role in mediating tumor survival, spreading, and metastasis [25]. Hence, CAIX has become an interesting target not only for cancer diagnosis but also for treatment. Its expression is increased in a wide variety of solid tumors (e.g., renal-cell carcinoma, brain, bladder, cervical, head and neck, breast, lung, sarcoma, and kidney cancers). Conversely, its expression in normal healthy tissues is usually low [26]. It is worth noting that the Von Hippel–Lindau mutation in clear-cell renal-cell carcinomas causes HIF1-α overexpression on the cell surface in this group of tumors [27].
Girentuximab (Rencarex) is a chimeric IgG1 mAb that binds CAIX and triggers antibody-dependent cell-mediated cytotoxicity (ADCC) by activating natural killer cells.
As an adjuvant treatment for high-risk clear-cell renal-cell carcinoma patients, its development as an unconjugated antibody was suspended because it showed no clinical benefit in a Phase III trial [28]. However, as a radioimmunoconjugate (i.e., 89Zr-Girentuximab), its safety and tolerance were proven in all patients, with a mean administered activity of 36.7 ± 1.1 MBq (range: 34.2–38.34 MBq) in a Phase I clinical trial [29].
In 2018, Hekman et al. [30] performed a Phase I dose-escalation study investigating the use of [111In] In-DOTA-Girentuximab-IRDye800CW in 15 patients with primary renal mass scheduled for surgery.
Four days after the administration of [111In] In-DOTA-Girentuximab-IRDye800CW (5, 10, 30, or 50 mg), SPECT/CT imaging was performed, whereas surgery was performed seven days after the infusion by using a gamma probe and NIR fluorescence camera. All CAIX-expressing tumors were visualized with SPECT/CT, and no uptake was observed in CAIX-negative tumors, proving the high sensitivity of the probe. Interestingly, an excellent concordance was also observed between the SPECT/CT and the NIR imaging. With a mean TBR of 2.5 at all protein doses, all clear-cell renal-cell carcinoma could be localized with gamma probe measurements during surgery. In summary, this Phase I study proved the safety of the [111In]In-DOTA-Girentuximab-IRDye800CW for targeting CAIX during clear-cell renal-cell carcinoma resection and it could be easily adopted for intraoperative guidance and decision-making.
  • mAbs targeting carcinoembryonic antigen (CEA)
Carcinoembryonic antigen (CEA) is a non-specific serum biomarker that is elevated in various malignancies, and it is highly expressed on the surface of colorectal cancer cells in more than 90% of all cases with a significant antigenic density. Conversely, its expression is 60 times lower on average in healthy tissue [31].
Labetuzumab (CEA-CIDE) is a humanized IgG1 mAb that has a high specificity to CEA. It has been deeply studied as a therapeutic drug, radiotracer, and antibody–drug conjugate for the treatment of several tumors.
A Phase I clinical trial was designed for the accurate preoperative evaluation and subsequent intraoperative identification of all tumor deposits in patients with colorectal peritoneal metastases undergoing cytoreductive surgery by using a dual-labeled version of Labetuzumab, the [111In]In-DOTA-Labetuzumab-IRDye800CW probe [31].
The results of the trial showed that [111In]In-DOTA-Labetuzumab-IRDye800CW was safe and enabled sensitive pre- and intraoperative imaging in patients who received 10 or 50 mg of the dual-labeled anti-CEA antibody conjugate. Interestingly, the preoperative imaging study showed previously undetected lymph node metastases in one case, while the intraoperative fluorescence signal allowed the identification of four previously undetected metastases in two cases. Moreover, in three patients, this multimodal imaging altered the decision-making process and the clinical and surgical strategy. A dose-expansion study was therefore warranted to further investigate the diagnostic accuracy and the potential implications of this dual-labeled anti-CEA antibody conjugate for patients with peritoneal metastases derived from colorectal cancer.

4. Monoclonal Antibodies (mAbs) Clinically Approved for the Treatment of Extra-Hematological Solid Malignancies Not Yet under Evaluation in Clinical Trials for T-FGS Purposes

In this section, mAbs clinically approved for the treatment of extra-hematological solid malignancies but not yet under clinical trial for T-FGS purposes are presented. For each of them, we will report the antigen targeted, mAb generic/commercial name and format, and clinical indication (Table 1). The aim is to stimulate future research and company developments in the field of T-FGS.
  • mAbs targeting the epidermal growth factor receptor (EGFR)
Necitumumab (Portazza) is an anti-EGFR recombinant human mAb of the IgG1 kappa isotype. With gemcitabine and cisplatin, it is used as a first-line treatment for patients affected by metastatic squamous non-small-cell lung cancer.
  • mAbs targeting the epidermal growth factor receptor 2 (HER2)
HER2 is a transmembrane receptor protein of 185 kDa, structurally related to the EGFR. In HER2-overexpressing tumors, an aberrant HER2 activity results in receptor dimerization (e.g., HER2/HER3), triggering complex intracellular signaling pathways that modulate cancer cell survival, proliferation, mobility, and invasiveness [32].
Trastuzumab (Herceptin) is a recombinant DNA-derived humanized IgG1 mAb that selectively binds with high affinity to the extracellular domain of HER2.
Trastuzumab is currently employed as an adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR negative or with one high-risk feature) breast cancers, in combination with paclitaxel for the first-line treatment of HER2-overexpressing metastatic breast cancers, and as a single agent for the treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease. Trastuzumab is also the basics of two approved antibody–drug conjugates (i.e., Ado-Trastuzumab Emtansine and Trastuzumab-Deruxtecan) for patients with HER2-positive metastatic breast cancer whose disease progresses after treatment with a combination of anti-HER2 antibodies and a taxane.
In combination with cisplatin and capecitabine or 5-fluorouracil, it is also used for the treatment of patients with HER2-overexpressing metastatic gastric or gastro-esophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.
Pertuzumab (Perjeta) is a recombinant humanized mAb that binds the extracellular dimerization domain (subdomain II) of HER2. By doing so, it blocks the ligand-dependent heterodimerization of HER2 with other HER family members (e.g., EGFR, HER3, and HER4). By inhibiting ligand-initiated intracellular cascades through two major signal pathways (i.e., mitogen-activated protein [MAP] kinase and phosphoinositide 3-kinase [PI3K]), Pertuzumab results in cell growth arrest and apoptosis. Moreover, Pertuzumab is a mediator of ADCC.
In 2017, the FDA granted regular approval to Pertuzumab for its use (i) in association with Trastuzumab and Docetaxel, for the treatment of HER2-positive metastatic breast cancers that had not been treated with prior anti-HER2 therapy or chemotherapy for metastatic disease; (ii) in association with Trastuzumab and chemotherapy, as a neoadjuvant treatment of HER2-positive, locally advanced, inflammatory, or early-stage breast cancers (either greater than 2 cm in diameter or node-positive); and (iii) as an adjuvant treatment of HER2-positive early-stage breast cancers at a high risk of recurrence.
  • mAbs targeting the vascular endothelial growth factor receptor 2 (VEGFR2)
VEGFR2 is a type III transmembrane kinase receptor composed of 1356 amino acids. It is made of an extracellular region consisting of seven immunoglobulin (Ig)-like domains, a short transmembrane domain, and an intracellular region containing a tyrosine kinase domain, split by a 70-amino-acid insert [19,20].
In adults, VEGFR-2 is mostly expressed on vascular endothelial cells and mediates several physiological and pathological processes driven by VEGF-A, including cell survival, proliferation, migration, and increased vascular permeability [19,20].
Ramucirumab (Cyramza) is a recombinant human IgG1 mAb targeting the extracellular domain of VEGFR2 and blocking the binding of VEGFR ligands, VEGF-A, VEGF-C, and VEGF-D. As a consequence, Ramucirumab inhibits the ligand-stimulated activation of VEGFR2, thereby inhibiting the ligand-induced proliferation and migration of human endothelial cells.
Ramucirumab is currently approved for the treatment of patients with advanced or metastatic gastric or gastro-esophageal junction adenocarcinomas, metastatic non-small-cell lung cancers, metastatic colorectal cancers, or hepatocellular carcinomas.
  • mAbs targeting platelet-derived growth factor receptor α (PDGFRα)
PDGFR-α is a receptor tyrosine kinase expressed on cells of mesenchymal origin [33,34]. Signaling through this receptor plays a role in cell proliferation, migration, mesenchymal stem cell differentiation, and VEGF-mediated angiogenesis [33,34].
The overexpression and activating mutations of PDGFRα in tumor cells have been demonstrated to contribute to tumor growth, metastasis, and the establishment of a tumor-supporting microenvironment. In this regard, a range of tyrosine kinase inhibitors with activity against PDGFRα have been investigated, aiming to reduce the proliferation and spreading of numerous solid cancers including sarcomas [33,34].
Olaratumab (Lartruvo) is a recombinant human IgG1 mAb that binds specifically to PDGFRα. It is used, in association with doxorubicin, for the treatment of adult patients with soft-tissue sarcoma with a histologic subtype for which an anthracycline-containing regimen is indicated and which is not amenable to curative treatment with radiotherapy or surgery.
  • mAbs targeting programmed death ligand-1 (PD-L1)
PD-L1 is expressed in several cell types: B cells, T cells, dendritic cells (DC), macrophages, mast cells, placenta, vascular endothelium, pancreatic islet cells, muscle, hepatocytes, epithelium, and mesenchymal stem cells. In pathological tumor cells, PD-L1 is overexpressed to escape immunologic surveillance and facilitate cancer growth. Several solid malignancies including melanoma, renal-cell carcinoma, non-small-cell lung cancer, thymoma, ovarian, and colorectal cancer express PD-L1 to create an immunosuppressive tumor microenvironment and escape T-cell cytolysis. Recently, several anti-PD-L1 mAbs have proven their safety and efficacy in causing durable antitumor immune effects with low toxicity for solid tumor types [35,36].
Atezolizumab (Tecentriq) is an Fc-engineered, humanized, non-glycosylated IgG1 kappa PD-L1-blocking mAb. It is clinically approved for the treatment of patients with non-small-cell lung cancers, small-cell lung cancers, hepatocellular carcinomas, melanomas, and alveolar soft part sarcomas.
Avelumab (Bavencio) is a human IgG1 lambda PD-L1 blocking mAb approved for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinomas.
Durvalumab (Imfinzi) is a human IgG1 kappa mAb that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80. It is indicated for the treatment of adult patients with unresectable, stage III non-small-cell lung cancer or with metastatic non-small-cell lung cancer with no sensitizing EGFR mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. Moreover, it is approved as a first-line treatment for adult patients with extensive-stage small-cell lung cancers or with locally advanced or metastatic biliary tract cancer. Additional indications are represented by unresectable hepatocellular carcinomas.
  • mAbs targeting the disialoganglioside GD2
Gangliosides (e.g., GM3, GM2, GM1, and GD1) are carbohydrate-containing sphingolipids highly expressed in healthy tissues. This explains why most subtypes are unsuitable targets for cancer therapy. On the contrary, the disialoganglioside GD2 is considered a tumor-associated antigen thanks to its minimal expression in healthy human tissues (e.g., lymphocytes, mesenchymal stem cells, dermal melanocytes, central nervous system, and peripheral sensory nerve fibers,) and good expression in several tumors (e.g., neuroblastomas, melanomas, retinoblastomas, and several Ewing sarcomas), and, hence, valued as a primary target for cancer immunotherapy [37,38,39] (see Figure 1). Not only its peculiar expression profile on solid tumors, but also its role in enhanced tumor cell proliferation, growth, motility, migration, adhesion, and invasion highlight its role for clinical targeting this tumor antigen with mAbs for therapeutic approaches [37,38,40,41]. Based on all these characteristics, the disialoganglioside GD2 has been ranked 12th among 75 potential targets for anti-cancer therapy in 2009 by the U.S. National Cancer Institute [38].
Dinutuximab (Unituxin) is a chimeric GD2-binding mAb employed for the treatment of children with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent multimodality therapy.
Dinutuximab-beta (Quarziba) is a murine-human chimeric anti-GD2 mAbs produced in Chinese hamster ovary (CHO) cells. In May 2017, the European Commission approved Dinutuximab-beta for the treatment of high-risk neuroblastoma in patients aged 12 months and above who have previously received induction chemotherapy and achieved at least a partial response followed by myeloablative therapy and stem cell transplantation. Patients with a history of relapsed or refractory neuroblastoma with or without residual disease are also potential candidates for its use.

5. Promising Monoclonal Antibodies (mAbs) for T-FGS Purposes Not Yet Clinically Approved for the Treatment of Extra-Hematological Solid Tumors

  • mAbs targeting the epidermal growth factor receptor (EGFR)
Nimotuzumab (h-R3, BIOMAb EGFR, Biocon, India; TheraCIM, CIMYM Biosciences, Canada; Theraloc, Oncoscience, Europe, CIMAher, Center of Molecular Immunology, Havana, Cuba) is a humanized anti-EGFR mAb, that was obtained in 1996 after the genetic modification of the parental murine molecule ior egf/r3 [42]. This mAb inhibits cell growth and angiogenesis, activates NK cells, induces cytotoxic T cells, and stimulates DC maturation. By hindering one of the EGFR immune-escape ways, this mAb restores MHC-I expression on tumor cells. Nimotuzumab has been deeply examined in seven clinical trials enrolling patients with inoperable head and neck tumors, concurrently with irradiation alone or irradiation plus chemotherapy [42].
According to a 2009 review [43], Nimotuzumab was approved for “squamous cell carcinoma in head and neck in India, Cuba, Argentina, Colombia, Ivory Coast, Gabon, Ukraine, Peru, and Sri Lanka; for glioma (pediatric and adult) in Cuba, Argentina, Philippines, and Ukraine; for nasopharyngeal cancer in China. It has been granted orphan drug status for glioma in the USA and for glioma and pancreatic cancer in Europe”. In April 2014, Daiichi Sankyo announced the discontinuation of a Phase III clinical trial conducted in Japan investigating Nimotuzumab for first-line therapy in patients with unresectable and locally advanced squamous-cell lung cancer based on safety issues occurring in certain patients receiving a combination of cisplatin, vinorelbine, and radiotherapy [44]. A phase I/II clinical trial evaluating Nimotuzumab-IRDye800CW as a NIR-I imaging probe for image-guided surgery is currently determining the safety, optimal dose, and imaging time for lung cancer resection ( NCT04459065).
  • mAbs targeting B7-H3 (CD276)
B7-H3 (CD276) is a member of the B7 family of immune checkpoint molecules, that is overexpressed in cancer cells and in activated tumor-infiltrating immune cells. B7-H3’s main function is to aid tumor cells to escape the surveillance of cytotoxic T cells and NK cells [45].
Several studies have demonstrated that B7-H3 is involved in the growth, spreading, and treatment resistance of several cancer types (e.g., lung cancer, colorectal cancer, breast cancer, prostate cancer, melanoma, gastric cancer, liver cancer, cervical cancer, and brain tumors), resulting in poor patient outcomes [46]. B7H3 has been also reported to be expressed specifically in the endothelial cells of tumors but not in normal vascular endothelium [47]. The significant difference in the expression levels of this immune checkpoint between healthy and tumor tissues can be adopted to develop targeting drugs with cancer-specific toxicity, without harm to normal tissue. B7-H3 is, therefore, a promising target for cancer therapy, including T-FGS. As a matter of fact, immunotherapies targeting B7-H3 have been developing rapidly, and many ongoing clinical trials are currently investigating the safety and efficacy profiles of this immune checkpoint molecule in cancer treatments ( NCT02982941, NCT02923180, NCT02381314, NCT04630769, NCT04634825, and NCT02475213).

6. Discussion

Several mAb-fluorophore conjugates have been effectively used for T-FGS in humans. We believe that the three most versatile ones are Cetuximab-IRDye800CW, Panitumumab-IRDye800CW, and Bevacizumab-IRDye800CW.
Among these three, examining the timing/dose of administration, safety profile, and side effects, we believe that Cetuximab-IRDye800CW has reached sufficient scientific evidence to support its role as a commercially available mAb for T-FGS in humans.
To reach the highest TBR and avoid a specific binding, Cetuximab should be administered intravenously 2 or 3 days before surgery as an unlabeled test/loading dose, followed by the fluorescently labeled one.
Although many solid tumor types have been investigated in clinical trials so far (i.e., head and neck cancer, esophageal cancer, pancreatic adenocarcinoma, brain neoplasm, rectal cancer, and penile cancer), several more can benefit from fluorescently labeled mAbs in the future to deliver highly individualized and personalized surgical approaches.
However, some key limitations of T-FGS have yet to be resolved.
Firstly, NIR-light penetration up to a few millimeters may limit the application of this modality for deep-seated lesions within solid organs (including minimal residual disease) and lymph node metastases. In this regard, more recent studies are evaluating dye with longer excitation wavelengths (i.e., NIR-II [wavelength: 1100–1350 nm], NIR-III [wavelength: 1600–1850 nm], and NIR-IV [wavelength: 2100–2300 nm] dyes) for achieving higher contrast, greater sensitivity, and improved penetration depths [48,49]. Despite the fact that no NIR-II fluorophores have been approved for clinical use in humans yet, some NIR-I dyes (e.g., ICG) have been shown to display bright emission tails over 1000 nm. This offers exciting opportunities for T-FGS [50].
Secondly, mAbs need to be given a few days before surgery, requiring an additional visit to the hospital for the patient. In this regard, new-generation small molecules have been recently developed for immunotherapy (i.e., affibodies and nanobodies), offering exciting new opportunities in the field of T-FGS. These small molecules could be adopted as theranostic tools to provide high-contrast images within a few hours after injection, overcoming the slow and low tumor uptake and the limited tumor penetration compared to traditional mAbs [51].
Thirdly, another limitation of fluorescently labeled mAbs conjugates is the quick quenching process, which means the loss of fluorescence due to a gain in stability from the electrons present in the fluorophore. Intraoperative sprayable targeted probes could overcome this problem. They will be applied to the region of interest (ROI) with a simple spray and make their clinical use simpler, more convenient, and possibly with fewer systemic side effects [3].
Finally, a thorough characterization of cancer surface antigen expression should become routine at diagnosis to decide which is the best mAb to deliver T-FGS at the time of surgical removal (precision medicine).

7. Conclusions

In this manuscript, the status of the clinical use of mAbs in cancer surgery was reviewed. This review aims to facilitate future research and molecular probe development in the field of T-FGS. This field is developing fast, and there is an opportunity to speed up the translation to the operating room by producing a few readily available “off-the-shelf” injectable fluorescence probes effective for several solid cancers.


This research received no external funding.

Data Availability Statement

The data presented in this study are available in this article.


This work is supported by the NIHR Oncology Translational Research Collaboration (NIHR O-TRC). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Funding statements for involved NIHR Biomedical Research Centers: NIHR The Royal Marsden and The Institute of Cancer Research BRC: This study represents independent research supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, UK. NIHR Imperial BRC: This study was supported by the NIHR Imperial Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. NIHR University College London Hospital BRC: This study was supported by researchers at the National Institute for Health Research University College London Hospitals Biomedical Research Centre. NIHR Oxford BRC: This work was supported by the NIHR Biomedical Research Centre, Oxford, UK. NIHR Cambridge BRC: This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. NIHR Manchester BRC: This research was supported by the NIHR Manchester Biomedical Research Centre. NIHR Southampton BRC: This report is independent research supported by the National Institute for Health Research Biomedical Research Centre Funding Scheme. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. NIHR Great Ormond Street Hospital BRC: All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. NIHR Bristol BRC: This study was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Guy’s and St Thomas’ BRC: This research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. AM was supported by an NIHR Clinician Scientist Fellowship (NIHR CS-2017-17-010).

Conflicts of Interest

The authors declare no conflicts of interest.


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Figure 1. Conjugation of anti-GD2 monoclonal antibodies (mAbs) with IRDye800CW and in vitro and in vivo binding experiments on neuroblastoma cells expressing the GD2 antigen.
Figure 1. Conjugation of anti-GD2 monoclonal antibodies (mAbs) with IRDye800CW and in vitro and in vivo binding experiments on neuroblastoma cells expressing the GD2 antigen.
Cancers 16 01045 g001
Table 1. Monoclonal antibodies (mAbs) clinically approved for the treatment of solid extra-hematological malignancies.
Table 1. Monoclonal antibodies (mAbs) clinically approved for the treatment of solid extra-hematological malignancies.
AntigenDrug Generic NameDrug Brand NameFormatClinical Indication
EGFRCetuximabErbituxChimeric IgG1Squamous-Cell Carcinoma of the Head and Neck, Colorectal Cancer
PanitumumabVectibixHuman IgG2Colorectal Cancer
NecitumumabPortrazzaHuman IgG1Squamous Non-Small-Cell Lung Cancer
HER2TrastuzumabHerceptinHumanized IgG1Breast Cancer
PertuzumabPerjetaHumanized IgG1Breast Cancer
VEGFBevacizumabAvastinHumanized IgG1Colorectal Cancer, Non-Squamous Non-Small Cell Lung Cancer, Glioblastoma, Renal-Cell Carcinoma, Cervical Cancer, Epithelial Ovarian, Fallopian Tube, Primary Peritoneal Cancer, Hepatocellular Carcinoma
VEGFR2RamucirumabCyramzaHuman IgG1Gastric Or Gastro-Esophageal Junction Adenocarcinoma, Non-Small-Cell Lung Cancer, Colorectal Cancer, Hepatocellular Carcinoma
PD-L1AtezolizumabTecentriqHumanized IgG1Non-Small-Cell Lung Cancer, Small-Cell Lung Cancer, Hepatocellular Carcinoma, Melanoma, Alveolar Soft Part Sarcoma
AvelumabBavencioHuman IgG1Merkel Cell Carcinoma
DurvalumabImfinziHuman IgG1Non-Small-Cell Lung Cancer, Small-Cell Lung Cancer, Biliary Tract Cancer, Hepatocellular Carcinoma
GD2DinutiximabUnituxinChimeric IgG1Neuroblastoma
Dinutiximab-betaQuarzibaChimeric IgG1Neuroblastoma
PDGFRαOlaratumabLartruvoHuman IgG1Soft-Tissue Sarcoma
Table 2. Monoclonal antibodies (mAbs) conjugated to the near-infrared I (NIR-I) fluorescent dye IRDye800CW for the intraoperative imaging of solid extra-hematological malignancies.
Table 2. Monoclonal antibodies (mAbs) conjugated to the near-infrared I (NIR-I) fluorescent dye IRDye800CW for the intraoperative imaging of solid extra-hematological malignancies.
DrugTumor TypePhaseRecruitment StatusEstimated Patient Identifier
Cetuximab-IRDye800CWEsophageal CancerPhase Ind401% of therapeutic dose (2.5 mg/m2); 10% of therapeutic dose (25 mg/m2); 25% of therapeutic dose (62.5 mg/m2) (iv)2 days before surgeryNCT04161560
Head and Neck CancerPhase I; Phase IIRecruiting7910 mg; 25 mg; 50 mg; 75mg unlabeled test/loading dose cetuximab + 15 mg Cetuximab-IRDye800CW; 75 mg unlabeled test/loading dose cetuximab + 25 mg Cetuximab-IRDye800CW (iv)4 days before surgeryNCT03134846
Head and Neck CancerPhase ITerminated1210 mg; 100 mg unlabeled test/loading dose of cetuximab + 50 mg dose of cetuximab-IRDye800 (iv)Prior to surgeryNCT01987375
Pancreatic AdenocarcinomaPhase IITerminated10100 mg unlabeled test/loading dose of cetuximab + 50 mg; 100 mg unlabeled test/loading dose of cetuximab + 100 mg (iv)2–5 days before surgeryNCT02736578
Brain NeoplasmPhase I; Phase IITerminated10unlabeled test/loading dose of cetuximab + 50 mg; unlabeled test/loading dose of cetuximab + 100 mg (iv)2–5 days before surgeryNCT02855086
Rectal CancerPhase Ind1575 mg unlabeled test/loading dose of cetuximab + 15 mg (iv)Prior to surgeryNCT04638036
Penile CancerPhase IRecruiting1515 mg unlabeled test/loading dose of cetuximab + 15 mg (iv)2 days before surgeryNCT05376202
Head and Neck CancerPhase IINot yet recruiting2075 mg unlabeled test/loading dose of cetuximab + 15 mg (iv)Prior to surgeryNCT05499065
Panitumumab-IRDye800CWHead and Neck CancerPhase IIRecruiting2550 mg (iv)ndNCT04511078
Head and Neck CancerPhase IICompleted2050 mg (iv)1–5 days before surgeryNCT03405142
Head and Neck CancerPhase ICompleted43nd (iv)Prior to surgeryNCT02415881
Head and Neck CancerPhase ICompleted1430 mg (iv)2-5 days before surgeryNCT03733210
Lung CancerPhase I; Phase IIActive, not recruiting30nd (iv)1–2 days or 3–5 days prior to surgeryNCT03582124
Brain TumorPhase I; Phase IINot yet recruiting120.006 mg/kg; 0.25 mg/kg; 0.5 mg/kg; 1.0 (with max cap dose 50 mg)1–5 days before surgeryNCT04085887
Brain TumorPhase I; Phase IIRecruiting2250 mg; 100 mg unlabeled test/loading dose of panitumumab + 50 mg; 100 mg; 100 mg unlabeled test/loading dose of panitumumab + 100 mg (iv)1–5 days before surgeryNCT03510208
Pancreatic AdenocarcinomaPhase I; Phase IIActive, not recruiting24100 mg unlabeled test/loading dose of panitumumab + 25 mg; 100 mg unlabeled test/loading dose of panitumumab + 50 mg; 100 mg unlabeled test/loading dose of panitumumab + 75 mg; 50 mg (iv)2–5 days before surgeryNCT03384238
Bevacizumab-IRDye800CWAdenomatous Polyposis ColiPhase ICompleted154.5 mg; 10 mg; 25 mg (iv)3 days before endoscopyNCT02113202
Rectal CancerPhase ICompleted304.5 mg (iv)2–3 days before endoscopyNCT01972373
Breast CancerPhase ICompleted304.5 mg (iv)4 h, 2 days before imaging and 3 days before surgeryNCT01508572
Breast CancerPhase I; Phase IICompleted264.5 mg; 10 mg; 25 mg; 50 mg (iv)3 days before surgeryNCT02583568
Soft-Tissue SarcomaPhase I; Phase IICompleted2310 mg; 25 mg; 50 mg (iv)Prior to surgeryNCT03913806
Esophageal CancerPhase ICompleted104.5 mg (iv)2 days before endoscopyNCT02129933
Esophageal CancerPhase ITerminated254.5 mg; 10 mg; 25 mg (iv)Prior to endoscopyNCT03558724
Hilar CholangiocarcinomaPhase I; Phase IIRecruiting1210 mg; 25 mg; 50 mg (iv)3 days before surgeryNCT03620292
Barrett EsophagusPhase IInd60nd (topical)5 min before endoscopyNCT03877601
Inverted PapillomaPhase IActive, not recruiting610 mg; 25 mg (iv)2–4 days before surgeryNCT03925285
Pancreatic CancerPhase I; Phase IITerminated264.5 mg; 10 mg; 25 mg; 50 mg (iv)3 days before surgeryNCT02743975
Pituitary TumorPhase IRecruiting154.5 mg; 10 mg; 25 mg (iv)Prior to endoscopyNCT04212793
Girentuximab-IRDye800CWRenal TumorPhase IRecruiting22nd (iv)7 days before surgeryNCT03558724
Labetuzumab-IRDye800CWColorectal CancerPhase I; Phase IIRecruiting29nd (iv)6–7 days before surgeryNCT03699332
Nimotuzumab-IRDye800CWLung CancerPhase I; Phase IIRecruiting3650 mg; 100 mg (iv)4–6 days before surgeryNCT04459065
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MDPI and ACS Style

Giuliani, S.; Paraboschi, I.; McNair, A.; Smith, M.; Rankin, K.S.; Elson, D.S.; Paleri, V.; Leff, D.; Stasiuk, G.; Anderson, J., on behalf of the Precision Surgery Group at the NIHR Oncology Translational Research Collaboration. Monoclonal Antibodies for Targeted Fluorescence-Guided Surgery: A Review of Applicability across Multiple Solid Tumors. Cancers 2024, 16, 1045.

AMA Style

Giuliani S, Paraboschi I, McNair A, Smith M, Rankin KS, Elson DS, Paleri V, Leff D, Stasiuk G, Anderson J on behalf of the Precision Surgery Group at the NIHR Oncology Translational Research Collaboration. Monoclonal Antibodies for Targeted Fluorescence-Guided Surgery: A Review of Applicability across Multiple Solid Tumors. Cancers. 2024; 16(5):1045.

Chicago/Turabian Style

Giuliani, Stefano, Irene Paraboschi, Angus McNair, Myles Smith, Kenneth S. Rankin, Daniel S. Elson, Vinidh Paleri, Daniel Leff, Graeme Stasiuk, and John Anderson on behalf of the Precision Surgery Group at the NIHR Oncology Translational Research Collaboration. 2024. "Monoclonal Antibodies for Targeted Fluorescence-Guided Surgery: A Review of Applicability across Multiple Solid Tumors" Cancers 16, no. 5: 1045.

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