Photodynamic therapy (PDT) induces cell death through local light activation of a photosensitizer (PS) and has been used to treat head and neck cancers. Yet, common PS lack tumor specificity, which leads to collateral damage to normal tissues. Targeted delivery of PS via antibodies has pre-clinically improved tumor selectivity. However, antibodies have long half-lives and relatively poor tissue penetration, which could limit therapeutic efficacy and lead to long photosensitivity. Here, in this feasibility study, we evaluate at the pre-clinical level a recently introduced format of targeted PDT, which employs nanobodies as targeting agents and a water-soluble PS (IRDye700DX) that is traceable through optical imaging. In vitro, the PS solely binds to cells and induces phototoxicity on cells overexpressing the epidermal growth factor receptor (EGFR), when conjugated to the EGFR targeted nanobodies. To investigate whether this new format of targeted PDT is capable of inducing selective tumor cell death in vivo, PDT was applied on an orthotopic mouse tumor model with illumination at 1h post-injection of the nanobody-PS conjugates, as selected from quantitative fluorescence spectroscopy measurements. In parallel, and as a reference, PDT was applied with an antibody-PS conjugate, with illumination performed 24h post-injection. Importantly, EGFR targeted nanobody-PS conjugates led to extensive tumor necrosis (approx. 90%) and almost no toxicity in healthy tissues, as observed through histology 24h after PDT. Overall, results show that these EGFR targeted nanobody-PS conjugates are selective and able to induce tumor cell death in vivo. Additional studies are now needed to assess the full potential of this approach to improving PDT.

Background Iatrogenic ureteral injury (IUI) following abdominal surgery has a relatively low incidence, but is associated with high risks of morbidity and mortality. Conventional assessment of IUI includes visual inspection and palpation. This is especially challenging during laparoscopic procedures and has translated into an increased risk of IUI. The use of near-infrared fluorescent (NIRF) imaging is currently being considered as a novel method to identify the ureters intraoperatively. The aim of this review is to describe the currently available and experimental dyes for ureter visualization and to evaluate their feasibility of using them and their effectiveness. Methods This article adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for systematic reviews. A systematic literature search was performed in the PubMed database. All included articles were screened for eligibility by two authors. Three clinical trial databases were consulted to identify ongoing or completed unpublished trials. Risk of bias was assessed for all articles. Results The search yielded 20 articles on ureter visualization. Two clinically available dyes, indocyanine green (ICG) and methylene blue (MB), and eight experimental dyes were described and assessed for their feasibility to identify the ureter. Two ongoing clinical trials on CW800-BK and one trial on ZW800-1 for ureter visualization were identified. Conclusions Currently available dyes, ICG and MB, are safe, but suboptimal for ureter visualization based on the route of administration and optical properties, respectively. Currently, MB has potential to be routinely used for ureter visualization in most patients, but (cRGD-)ZW800-1 holds potential for this role in the future, owing to its exclusive renal clearance and the near absence of background. To assess the benefit of NIRF imaging for reducing the incidence of IUI, larger patient cohorts need to be examined. Electronic supplementary material The online version of this article (10.1007/s10151-019-01973-4) contains supplementary material, which is available to authorized users.

Background: Fluorescent imaging using indocyanine green (ICG) is an emerging technique that aids the surgeon with intraoperative decision making during upper gastrointestinal cancer surgery. In this systematic review we aim to provide an overview of current practice of fluorescence imaging using ICG during esophagectomy, and to show how this technology can prevent surgical morbidity, such as anastomotic leakage, graft necrosis and chylothorax. Methods: The PRISMA standard for systematic reviews was used. The PubMed and Embase database were searched to identify articles matching our systematic literature search. Two authors screened all included articles for eligibility. Risk of bias was assessed for all included articles. Results: A total of 25 articles were included in this review: 22 articles on perfusion assessment, and three on the detection of chyle fistula. Five out of 22 articles concerning perfusion assessment evaluated fluorescence signals in quantitative values. In 20 articles the pooled incidence of anastomotic leakage and graft necrosis in the ICG group was 11.10% (95% CI: 8.06-15.09%) and in eight studies the pooled change in management rate was 24.55% (95% CI: 19.16-30.88%). After change in management, the pooled incidence of anastomotic leakage and graft necrosis was 14.08% (95% CI: 6.55-27.70%). A meta-analysis showed that less anastomotic leakages and graft necrosis occur in the ICG group (OR 0.30, 95% CI: 0.14-0.63). Three case-reports (N=3) were identified regarding chyle fistula detection, and ICG lymphography detected the thoracic duct in all cases and the chyle fistula in one case. Conclusions: Fluorescence imaging using ICG is a promising and safe technology to reduce surgical morbidity after esophagectomy with continuity restoration. ICG fluorescence angiography showed a reduction in anastomotic leakage and graft necrosis. Future studies are needed to demonstrate the feasibility of ICG lymphography for chyle fistula detection.