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Glioblastoma is a fast‐growing and aggressive form of brain cancer. Even with maximal treatment, patients show a low median survival and are often subjected to a high recurrence incidence. The currently available treatments require multimodal management, including maximal safe surgical resection, followed by radiation and chemotherapy. Because of the infiltrative glioblastoma nature, intraoperative differentiation of cancer tissue from normal brain parenchyma is very challenging, and this accounts for the low rate of complete tumor resection. For these reasons, clinicians have increasingly used various intraoperative adjuncts to improve surgical results, such as fluorescent agents. However, most of the existing fluorophores show several limitations such as poor selectivity, photostability, photosensitization and high costs. This could limit their application to successfully improve glioblastoma resection. In the present perspective, we highlight the possibility to develop next‐generation fluorescent tools able to more selectively label cancer cells during surgical resection. [ABSTRACT FROM AUTHOR]

Abstract Glioblastoma is a fast‐growing and aggressive form of brain cancer. Even with maximal treatment, patients show a low median survival and are often subjected to a high recurrence incidence. The currently available treatments require multimodal management, including maximal safe surgical resection, followed by radiation and chemotherapy. Because of the infiltrative glioblastoma nature, intraoperative differentiation of cancer tissue from normal brain parenchyma is very challenging, and this accounts for the low rate of complete tumor resection. For these reasons, clinicians have increasingly used various intraoperative adjuncts to improve surgical results, such as fluorescent agents. However, most of the existing fluorophores show several limitations such as poor selectivity, photostability, photosensitization and high costs. This could limit their application to successfully improve glioblastoma resection. In the present perspective, we highlight the possibility to develop next‐generation fluorescent tools able to more selectively label cancer cells during surgical resection.

Introduction: Probe-based confocal laser endomicroscopy (pCLE) is an innovative technique providing real-time, in vivo optical biopsies. A previous ex vivo phase of the study (PERSEE) allowed identifying accurate pCLE criteria for the diagnosis of hepatic and peritoneal surgical specimens. This study aimed at evaluating the pCLE role for in vivo intra-abdominal tissue characterization during digestive cancer surgical procedures.Methods: Between October 2014 and July 2015, consecutive patients diagnosed with digestive cancers and scheduled for a surgical resection or an exploratory laparoscopy were prospectively enrolled. Endomicroscopic images were acquired using a motorized Confocal Miniprobe™ with a bending distal tip providing easy access to abdominal organs. It was connected to an endomicroscopy system that allowed near-infrared illumination (at a wavelength of 785 nm) in conjunction with indocyanine green for contrast agent. A live audiovisual transmission was established between the surgeon and the pathologist for real-time interpretation of optical biopsies. Intraoperative pCLE performance for the diagnosis of suspicious nodules was assessed using corresponding surgical histopathology as reference standard.Results: 21 consecutive patients were successfully enrolled. Live audiovisual transmission between the surgeon and the pathologist was successfully established in all cases. 62 pCLE sequences were acquired from different tissues [peritoneum (n = 27), liver (n = 21), lymph node (n = 4), diaphragm (n = 3), colon (n = 3), stomach (n = 2), and adrenal gland (n = 2)]. Malignant tissues were identified by fluorescently enhanced irregular cancerous tubes contrasting with dark glandular lumen and extracellular matrix. pCLE sensitivities and specificities were 67% and 100%, and 38% and 100% for peritoneal and hepatic carcinogenesis, respectively. One benign incident was reported during the trial with no patient consequence.Conclusions: Real-time intraoperative pCLE with near-infrared illumination is feasible and safe, provides additional information in terms of tissue characterization, and, in combination with telepathology, allows interactive collaboration between the surgeon and the pathologist during surgical procedures. Trial registration clinicaltrials.gov Identifier: NCT02312167. [ABSTRACT FROM AUTHOR]

Glioblastoma is a fast-growing and aggressive form of brain cancer. Even with maximal treatment, patients show a low median survival and are often subjected to a high recurrence incidence. The currently available treatments require multimodal management, including maximal safe surgical resection, followed by radiation and chemotherapy. Because of the infiltrative glioblastoma nature, intraoperative differentiation of cancer tissue from normal brain parenchyma is very challenging, and this accounts for the low rate of complete tumor resection. For these reasons, clinicians have increasingly used various intraoperative adjuncts to improve surgical results, such as fluorescent agents. However, most of the existing fluorophores show several limitations such as poor selectivity, photostability, photosensitization and high costs. This could limit their application to successfully improve glioblastoma resection. In the present perspective, we highlight the possibility to develop next-generation fluorescent tools able to more selectively label cancer cells during surgical resection., Competing Interests: Dr. Francesco Acerbi received honoraria from Carl Zeiss Meditec for lectures in International Meetings. Other authors declare no conflict of interest., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Purpose: Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP(®) peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors.Procedures: Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP(®) variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP(®) variants in multidimensional space of spectral parameters.Results: The fluorescently labeled pHLIP(®) variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP(®) peptide.Conclusions: Different cargo molecules conjugated with pHLIP(®) peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP(®)-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions. [ABSTRACT FROM AUTHOR]

Objective The identification of cranial nerves is one of the most challenging goals in the dissection of skull base meningiomas. The authors present an application of sodium fluorescein (SF) in skull base meningiomas with the purpose of improving the identification of cranial nerves. Design A prospective study within-subjects design. Setting Hospital Ernesto Dornelles, Porto Alegre, Brazil. Participants Patients with skull base meningiomas. Main Outcomes Measures Cranial nerve identification. Results The group of nine meningiomas was composed of one cavernous sinus, three petroclival, one tuberculum sellae, two sphenoid wing, one olfactory groove, and one temporal floor meningioma. The SF enhancement in all tumors was strong, and the contrast with cranial nerves clearly evident. There were one definite olfactory nerve deficit, one transient abducens deficit, and one definite hemiparesis. All lesions were resected (Simpson grades 1 and 2). The analysis of the difference of the delta SF wavelength between themeningiomas and cranial nerve contrast was performed by the Wilcoxon signed rank test and showed p = 0.011. Conclusions The contrast between the enhancedmeningiomas and cranial nerves was evident and assisted in the visualization and microsurgical dissection of these structures. The anatomical preservation of these structures was improved using the contrast. [ABSTRACT FROM AUTHOR]

Local re-occurrence of cancer in patients with solid tumors is currently the most common reason for failure of treatment strategies. This fact indicates that prevailing approaches for tumor resection can cure only 50% of patients. A major cause of failure in tumor resection is off-target drug cytotoxicity and lack of sensitivity in tumor detection methods. These disadvantages are addressed with the development of targeted therapy and diagnostics, which significantly aid treatment strategies. Targeted diagnostics exploit properties of tumor cells that show significant up-regulation of tumor biomarkers. These biomarkers are targeted by a homing ligand attached to a fluorophore for visual inspection during surgery. However, these approaches suffer from disadvantages like high autofluorescence from background tissues, tissue absorption, and scattering, resulting in decreased image sensitivity and resolution. The use of near-infrared (NIR) fluorophores to overcome these drawbacks has generated unprecedented interest among researchers. The NIR window lies within the range of 650 to 1,700 nm, which results in reduced absorption and scattering by the tissues, thereby providing deeper tissue penetration and reduced autofluorescence. NIR fluorophores can be designed to target tumor biomarkers such as prostate specific membrane antigen (PSMA) or folate receptors found over-expressed on cancer tissues. These targeted fluorophores consist of small-molecule ligands conjugated with NIR dyes that bind with high specificity to PSMA and folic acid receptors. In this protocol, we have extensively described the methodology for the synthesis of targeted NIR agents for PSMA (DUPA-NIR bioconjugate) and folic acid (folate-NIR bioconjugate), along with detailed steps for preclinical evaluation. Procedures to calculate the binding affinity to cancer cells in vitro are described, along with uptake and biodistribution in different mice models in vivo. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Synthesis and purification of DUPA and folate-peptide linkers via a SPPS strategy Basic Protocol 2: Conjugation, purification, and characterization of targeted bioconjugates with NIR probe for deep-tissue imaging applications Basic Protocol 3: In vitro evaluation of binding affinity of targeted DUPA-NIR and folate-NIR bioconjugates using a spectrophotometer Basic Protocol 4: Induction of tumor in mice to develop CDX or metastatic tumor models Basic Protocol 5: Intravenous administration of targeted DUPA-NIR and folate-NIR bioconjugates in mouse CDX or metastatic tumor models for deep-tissue NIR imaging and tumor resection., (© 2022 Wiley Periodicals LLC.)