Delta-Aminolevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials

Abstract

Fluorescence imaging is an emerging clinical technique for real-time intraoperative visualization of tumors and their boundaries. Though multiple fluorescent contrast agents are available in the basic sciences, few fluorescence agents are available for clinical use. Of the clinical fluorophores, delta aminolevulinic acid (5ALA) is unique for generating visible wavelength tumor-specific fluorescence. In 2017, 5ALA was FDA-approved for glioma surgery in the United States. Additionally, clinical studies suggest this agent may have utility in surgical subspecialties outside of neurosurgery. Data from dermatology, OB/GYN, urology, cardiothoracic surgery, and gastrointestinal surgery show 5ALA is helpful for intraoperative visualization of malignant tissues in multiple organ systems. This review summarizes data from English-language 5ALA clinical trials across surgical subspecialties. Imaging systems, routes of administration, dosing, efficacy, and related side effects are reviewed. We found that modified surgical microscopes and endoscopes are the preferred imaging devices. Systemic dosing across surgical specialties range between 5 and 30 mg/kg bodyweight. Multiple studies discussed potential for skin irritation with sun exposure, however this side effect is infrequently reported. Overall, 5ALA has shown high sensitivity for labeling malignant tissues and providing a means to visualize malignant tissue not apparent with standard operative light sources.

A Surgical Pen-Type Probe Design for Real-Time Optical Diagnosis of Tumor Status using 5-Aminolevulinic acid

“…In Fig. 10, the external irradiation optical source power (laser module) of a conventional surgical microscope was 55-160 mW/cm 2 [4], [15], [18], [25]- [29], and the working distance was 15-30 cm [4,15,18,23,25,29]. However, the external irradiation optical intensity will have losses of approximately 58 % when the working distance is above the minimum of 200 mm [30].…”

“…4 shows the fabrication of a pen-type probe that was created via the 3 D printing technique. The overall size and weight of the pen-type probe were 17 mm × 2.5 mm and 32 g (± 2 g), respectively; the weight of the conventional surgical microscope is 6.0 kg [20]- [23]. Thus, the pentype probe is lighter than the conventional surgical microscope.…”

“…In addition, they allow limited adjustment of the observed beam angles (maximum 30°) and working distances of 15-30 cm/cm 2 [15]- [24]. Because a surgical camera uses a high-energy light source (55-160 mW/cm 2 ) for the electromotive force of fluorescence emission, optical source beam energy loss (above 58%) can occur at the working distance (15-30 cm), and strong ambient light can be observed around the tissue (photobleaching) [10], [15], [23,24]. Thus, the surgical microscope is difficult to operate for tissue observation owing of the limitations of beam working distance (WD) control and adjustment of the left and right of the camera [16,17].…”

“…Thus, the surgical microscope is difficult to operate for tissue observation owing of the limitations of beam working distance (WD) control and adjustment of the left and right of the camera [16,17]. In addition, surgical diagnostic systems are not portable because of their large size [10], [23].…”

Photodynamic diagnosis and photodynamic therapy of colorectal cancer in vitro and in vivo

“…82 No studies utilizing any modied third-generation porphyrins for the PDD of CRC were found. 83 Chlorins. A study by Gavrina et al (2018), explored the PDT efficacy of Chlorin e6 (Ce6) conjugated to polyvinyl alcohol (PVA) nanoparticles in CRC CT26 xenogra models.…”