Photodiagnosis and photodynamic therapy

Abstract

Photodiagnosis (PD) and photodynamic therapy (PDT) are highly active fields in translational medicine. This concept is partly established in a variety of medical applications, but it also constitutes a still-growing field in biomedical research, where the focus is on cross-functional collaborations between researchers, technicians, industry and clinicians. The combined use of a drug and light for diagnostic and therapeutic medical application is a vision that goes back a long way. In modern times, it was discovered by the Tirolean researchers Hermann von Tappeiner and Oscar Raab at the Institute of Pharmacology at the Ludwig Maximilians University in Munich more than 100 years ago. By now, PD and PDT are being medically used in medical disciplines such as gastroenterology, urology, neurosurgery, head-and-neck surgery, gynecology, dermatology, oncology, antimicrobial treatment and many other disciplines. PD and PDT have both become state-of-the-art and are approved by the Food and Drug Administration and European Union for various indications. Ongoing further developments are continuously presented and discussed during specific PDT conferences, such as PD&PDT-Update 2018 in Kochel a. See (Bavaria) and IPA 2019 in Boston (United States). Special highlights of such meetings are the multidisciplinary interactions and the discussions, which are a prerequisite for successful translational research and translation of new technology in the clinic. Unfortunately, due to the worldwide CORONA crisis, most of the 2020 meetings are postponed or canceled. Publishing of translational research can partly take over the personal sharing of interesting PD and PDT research. The present issue reflects the actual status quo and latest aspects of laser light application in PD and PDT. Focusing on translational clinical studies, Papayan et al describe a video endoscopy system to acquire both fluorescence images (VIS/NIR) and a white-light image of the same area during bronchoscopy (e201900019). Clinical examples illustrate the system capability and describe the procedure for photodynamic theranostics in patients suffering from central lung cancer. Malik reviews the basics of aminolevulinic acid- (ALA-) PDT applications and describes the clinical use of ALA for fluorescence-guided resection in neurosurgery, an application that also demonstrates the method's potential for theranostics (e201900022). Different aspects of ALA-PDT mechanisms are discussed, and prospects for future research and applications are described. In a contribution from dermatology, innovative applications of ALA-PDT for common skin diseases are presented by Shi et al (e201900028). As pain is the main adverse reaction of ALA-PDT here, daylight PDT (D-PDT) and an optimized PDT protocol are clinically investigated, with the aim to reduce the pain through a change of light sources and standard therapeutic parameters. Both aspects represent current trends in the strive for improvements in the clinical application of ALA-PDT. Loshenov et al show intraoperative fluorescence diagnosis of the bladder wall with an excitation wavelength of 635 nm in a clinical trial followed by fluorescence-guided transurethral resection (e201900026). Special clinical interest is given to the identification of the fluorescing boundaries of the tumor and of small fluorescing tumor foci, which cannot be detected under white-light cystoscopy. What looks promising is that, by means of this red-wavelength approach, it might become possible to detect tumors including those in the deeper tissue layers. Bigge et al contribute a specific clinical case report on a combination therapy concept using PDT plus laser-assisted drug delivery, used for the treatment of an immunosuppressed patient showing multiple actinic keratosis and recurrent squamous cell carcinoma (e201900037). Following this therapeutic approach, disease stabilization over a follow-up period of 2 years could be achieved with six sessions of combination therapy. Prior to clinical trials, dedicated background and feasibility investigations must be conducted, and thorough testing of new procedures, equipment and parameters is required. In this way Lilge et al report on the use of an innovative photosensitizer, a Ru(II) polypyridyl complex (TLD1433), for the treatment of bladder carcinomas experimentally used in vitro and in an in vivo orthotopic model (e201900032). The electrostatic properties of the normal urothelium vs a tumor-compromised urothelium provide for a high selective uptake ratio. In in vivo models, successful tumor necrosis close to 1.5 mm in depth could be achieved after activation with light in the 520 to 540 nm range. As oxygen consumption plays a major role in PDT and photobiomodulation (PBM), Gerelli et al present its effects on oxygen consumption in the chorioallantoic membrane (CAM) of chicken embryos in vivo under hypoxia (e201900025). Specifically, ALA-induced protoporphyrin IX (PPIX) was used to probe the oxygen partial pressure (pO2) in the CAM by time-resolved spectroscopy of its delayed fluorescence. The clearing and drainage function of the recently rediscovered meningeal lymphatic system is demonstrated by Semyachkina-Glushkovskaya et al by means of the photostimulation effect of using light of a wavelength of 1268 nm (e201900036). Their in vivo experiments also show the effects of photostimulation on the permeability of the lymphatic endothelium to macrophages. These findings may encourage new strategies for alternative nonpharmacological therapy approaches to brain diseases via specific modulated photostimulation. Multidrug resistance in pathogenic bacteria is a common burden and is classified as one of the major threats to human health worldwide. Maisch updates about new strategies and ideas to prevent spread and to control antibiotic-resistant bacteria (e201900033). In his review, he summarizes the current status of the photodynamic principle and new developments in the field of photoantimicrobials. In addition, Malik gives insight into PDT-related investigations aimed at developing novel therapeutic approaches against multidrug resistance (e201900030). A proposal was made that antimicrobial PDT as an adjuvant, in combination with antibiotics or other toxic molecules, may open a new therapeutic window for topical life-threatening infections, without induction of further resistance. Hally et al review recent applications of water-soluble proteins as carriers for photosensitizing molecules for antimicrobial PDT (e201900031). Taking advantage of the spontaneous interaction between water-soluble proteins endowed with hydrophobic cavities and the otherwise insoluble photosensitizing compounds, this concept appears promising for obtaining an efficient delivery system for antimicrobial PDT. Finally, although some laser medical techniques appear completely established, there are sometimes innovative investigations demonstrating a remarkable development of traditional clinical applications based on new technologies. In this regard, Strittmatter et al present a general overview of ongoing research and development in laser-induced lithotripsy, comprising the historical background, insight into actual laboratory work and lessons learned (e201900029). Nowadays, stones can be dusted, which makes it possible to flush tiny fragments out of the urinary system, thus avoiding the need to remove larger fragments separately. With regard to treatment safety, the autofluorescence of stones can be used either to verify a stone-free environment or to introduce safety measures such as the differentiation of stone from tissue. We hope that these brief appetizers motivate you to become deeply interested in the exchange of the experience of modern laser medical and biophotonic translational research and developments. You are invited to send us your feedback and propose new topics or features, and we welcome your excellent work to be published in Translational Biophotonics. Last but not least, we wish all readers an enjoyable time by discovering this issue dedicated to “PD” and “PDT.” We hope that you can rediscover proven practices and will be inspired by new suggestions. We hope that this issue of Translational Biophotonics will find you, your research group and also your families healthy.

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