Biomodulatory approaches to photodynamic therapy for solid tumors

Abstract

Photodynamic Therapy (PDT) uses a photosensitizing drug in combination with visible light to kill cancer cells. PDT has an advantage over surgery or ionizing radiation because PDT can eliminate tumors without causing fibrosis or scarring. Disadvantages include the dual need for drug and light, and a generally lower efficacy for PDT versus surgery. This minireview describes basic principles of PDT, photosensitizers available, and aspects of tumor biology that may provide further opportunities for treatment optimization. An emerging biomodulatory approach, using methotrexate or Vitamin D in combination with aminolevulinate-based PDT, is described. Finally, current clinical uses of PDT for solid malignancies are reviewed.

New Approaches to Photodynamic Therapy from Types I, II and III to Type IV Using One or More Photons

“…The nonfluorescent PS precursor 5-aminolevulinic acid (5-ALA, trade name Levulan®) enhances the intrinsic production of protoporphyrin IX (PPIX) in mitochondria, which is activated by light illumination (~ 635 nm) following accumulation at the treatment site leading to the effective generation of reactive oxygen species within treated cells and triggering cell death [17,68,69]. The clinical use of topically applied 5-ALA for PDT was first introduced in 1990 [70] and followed by a wide range of clinical and preclinical studies for the PDT treatment of bladder cancer [71][72][73], chronic polyarthritis [74], malignant glioma [75], nonmelanoma skin cancers such as actinic keratosis (in combination with fluorescence dosimetry) [69,76], Barret's oesophagus and even multidrug resistant leukemia, the latter without much success [77]. In 2013 Bader et al reported a clinical trial using hexaminolevulinate (HAL), a 5-ALA derivative, for the PDT of bladder cancer in humans.…”

“…chlorins, bacteriochlorins and phthalocyanines) were developed. Third generation PSs were designed to improve selective tumour targeting and drug accumulation by conjugating common PSs to carriers such as cholesterol, antibodies, and liposomes and therefore reduce unwanted damage to healthy tissues [5,42,69,78]. The section on targeted PDT below (4.7) will cover these developments in more detail.…”

“…The choice of light source depends on its cost, reliability, size, available fluence rate (light dose), the PS used, the location of the disease site, as well as on the treatment depth inside tissue that needs to be achieved [5,32,69]. Ideally excitation wavelengths in the red or NIR ("tissue window") are best, as the penetration depth in tissues is improved compared to the UV or visible range.…”

“…The main types of light sources that can be used for PDT are lasers, LEDs and filtered lamps (e.g. fluorescent tubes, metal halide, xenon arc, high pressure and incandescent filament lamps) [10,28,69]. Since the invention of the Finsen lamp there has been much technological development leading to improved light sources.…”

“…LED arrays can be configured easily allowing to accurately define irradiation areas of different geometries, e.g. linear arrays can be used endoscopically [10,28,69].…”