Targeted optical fluorescence imaging: a meta-narrative review and future perspectives

Purpose The aim of this review is to give an overview of the current status of targeted optical fluorescence imaging in the field of oncology, cardiovascular, infectious and inflammatory diseases to further promote clinical translation. Methods A meta-narrative approach was taken to systematically describe the relevant literature. Consecutively, each field was assigned a developmental stage regarding the clinical implementation of optical fluorescence imaging. Results Optical fluorescence imaging is leaning towards clinical implementation in gastrointestinal and head and neck cancers, closely followed by pulmonary, neuro, breast and gynaecological oncology. In cardiovascular and infectious disease, optical imaging is in a less advanced/proof of concept stage. Conclusion Targeted optical fluorescence imaging is rapidly evolving and expanding into the clinic, especially in the field of oncology. However, the imaging modality still has to overcome some major challenges before it can be part of the standard of care in the clinic, such as the provision of pivotal trial data. Intensive multidisciplinary (pre-)clinical joined forces are essential to overcome the delivery of such compelling phase III registration trial data and subsequent regulatory approval and reimbursement hurdles to advance clinical implementation of targeted optical fluorescence imaging as part of standard practice.

F-actin dynamics transform filopodial bridges into intercellular nanotubes capable of distant cell communication

A novel actin-based bridge connecting cells has been recognized as a new pathway for the distant transport of cytoplasmic components, viruses, or pathogenic substances between cells. However, it is not yet known how such a fine structure extends over several hundred micrometres and remains robust for several hours. Using optical fluorescence imaging methods, we found that random contact promotes the formation of filopodial bridges through N-cadherin interactions between filopodia, which are slender actin-rich plasma membrane protrusions. These filopodial bridges eventually evolve into a single actin-based bridge (intercellular nanotube) that connects two cells via an intermediate state that involves a helical structure. Surprisingly, the twisting of two filopodia is likely to result from the rotational motion of actin filaments inside the filopodia by myosin V. The accumulated torsion of the filopodia triggers the release of one of the paired filopodia, whose end is attached to the other cell body by an N-cadherin cluster. The resulting retraction of the filopodium by retrograde F-actin flow leaves a single bridge. The N-cadherin/catenin cluster is likely to form a synapse between the intercellular nanotube and the cell body. This study sheds light on the formation mechanism of the filopodial bridge-based intercellular nanotubes for long-distance communication between cells.