Background Despite significant improvements in preoperative workup and surgical planning, surgeons often rely on their eyes and hands during surgery. Although this can be sufficient in some patients, intraoperative guidance is highly desirable. Near-infrared fluorescence has been advocated as a potential technique to guide surgeons during surgery. Methods A literature search was conducted to identify relevant articles for fluorescence-guided surgery. The literature search was performed using Medical Subject Headings on PubMed for articles in English until November 2022 and a narrative review undertaken. Results The use of invisible light, enabling real-time imaging, superior penetration depth, and the possibility to use targeted imaging agents, makes this optical imaging technique increasingly popular. Four main indications are described in this review: tissue perfusion, lymph node assessment, anatomy of vital structures, and tumour tissue imaging. Furthermore, this review provides an overview of future opportunities in the field of fluorescence-guided surgery. Conclusion Fluorescence-guided surgery has proven to be a widely innovative technique applicable in many fields of surgery. The potential indications for its use are diverse and can be combined. The big challenge for the future will be in bringing experimental fluorophores and conjugates through trials and into clinical practice, as well as validation of computer visualization with large data sets. This will require collaborative surgical groups focusing on utility, efficacy, and outcomes for these techniques.

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Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.

Surgery is the cornerstone of curative-intent treatment of patients with solid cancers. Complete removal of the tumor is pivotal for prolonged survival outcomes. Unfortunately, tumor-positive resection margins occur in 8-70% of cases depending on cancer type. Evidently, there is an unmet need for a technique to improve tumor detection and margin assessment in real-time during surgery. Intraoperative tumor-targeted near-infrared (NIR) fluorescence imaging enables visualization of (residual) tumor rapidly, non-invasively and in real-time with high spatial accuracy. The development and clinical translation of newly designed tumor-targeted NIR imaging agents is essential, because none of the available imaging agents can be used in all tumor types due to variable protein expression profiles. Development and clinical translation of imaging agents is a costly and time-consuming process, as it comprises many different stages and requires strict regulatory assessments to ensure patient safety and agent efficacy. To illustrate this process, a brief overview of the development and/or clinical translation of four promising tumor-targeted NIR imaging agents is presented, each currently in a different phase: OTL-38 (Pafolacianine - Cytalux), SGM-101, cRGD-ZW800-1 and AKRO-QC-ICG.