5‐ALA in the management of malignant glioma

Abstract

Background: Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard. Aims: This review intends to provide an overview over current status, significance, limitations, and future perspectives of 5-ALA based fluorescence guided surgery and photodynamic therapy for brain tumor patients. Materials and Methods: From peer reviewed publications on the many aspects connected with this topic, those with potential clinical relevance were selected and put in the context of our own experience. Results and Discussion: The high tumor selectivity of accumulation of fluorescent protoporphyrin IX (PpIX) after systemic administration of 5-ALA enables intra-operative fluorescence guidance, which is unimpaired by brainshift and does not require expensive equipment. The neurosurgical aim of complete resection of enhancing tumor can now more easily be achieved, which improves prognosis in these patients. Nevertheless, despite better surgery tumors will inevitably recur. In order to further prolong survival, the phototoxic properties of PpIX are presently being exploited in clinical trials of post-operative or interstitial photodynamic therapy (PDT). Conclusion: 5-ALA based fluorescence guidance and PDT offer an intriguing new option for the management of malignant gliomas. Lasers Surg. Med. 50:399-419, 2018.

Detecting neuroinflammation in the brain following chronic alcohol exposure in rats: A comparison between in vivo and in vitro TSPO radioligand binding

“…Increases in peripheral ALA have been shown to increase brain levels of PPIX 2.5‐fold in the mouse cortex (Demyanenko, Uzdensky, Sharifulina, Lapteva, & Polyakova, ). Clinically, oral administration of ALA is used to delineate gliomas via the fluorescent properties of PPIX, which gliomas accumulate in greater amounts than non‐malignant brain tissue (Stepp & Stummer, ), providing evidence that in humans increases in ALA lead to elevations of PPIX. Finally, pre‐treatment with 200 mg/kg ALA, which is converted to PPIX, decreased [ 11 C]PBR28 uptake in TSPO‐rich regions, such as the heart and lungs, by 57%–80%, respectively, in rats in vivo using PET (Ozaki et al., ).…”

Compact and contactless reflectance confocal microscope for neurosurgery

“…In addition, the concept entails some practical advantages. A combination of NIR illumination with fibre-based detection reduces the system's susceptibility to room light interference, which is normally in the visible light spectrum [31], implying that surgical procedures could be performed under normal lighting conditions [11]. Longer wavelengths would further decrease interference of ambient light as well as increase the imaging depth [19,29], but at the expense of a reduced spatial resolution.…”

“…Apart from system configuration, the employed contrast mechanism also affects the feasibility of adopting an imaging method for intraoperative use. Fluorescence guided surgery, as one of the most commonly exploited techniques, has provided useful information on the cellular and molecular scale for brain tumour resection [2,[9][10][11]. However, the use of fluorescent dyes in the human brain is limited by many factors, such as tumour selectivity, fluorophore uptake due to the blood-brain-barrier, fluorophore brightness and toxicity, photobleaching, injection timings, dose constraints [12][13][14].…”

The Yin and Yang of PDT and PTT

“…Several Phase I/II clinical trials have demonstrated improvement in overall survival times and progression‐free survival . As recently reviewed by Stepp and Stummer , the combination in the use of ALA‐PpIX for fluorescence image‐guided tumor resection followed by intracavitary photodynamic therapy is particularly compelling. Interstitial PDT, exploiting the tumor selectivity of ALA‐PpIX, has also been investigated for destruction of metastatic tumors in the brain and has shown significant efficacy .…”