Photodynamic Therapy Device for Treating Glioblastoma

Overview

Glioblastoma (GBM) is an aggressive brain cancer characterized by rapid cell growth in the frontal and temporal lobes. Current treatment methods involve surgical resection of the tumor with help from 5-aminolevulinic acid (5-ALA), a photosynthesizing agent that binds to cancerous glial cells at a much higher rate than normal cells and illuminates cancerous cells under near-infrared light. New studies indicate that 5-ALA infused glial cancer cells can undergo apoptosis when exposed to high amounts of near-infrared (NIR) light, but current procedures require multiple open brain surgeries to administer this photodynamic light. With the 5-year rate of survival being 6% due to residual cancer cell growth, PSU College of Medicine has tasked us to create an implantable device to deliver near-infrared light to patients with glioblastomas to reduce tumor recurrence after surgery in an environment outside the operating room.

Objectives

The primary focus of our project is to create a portable device that is able to administer photodynamic therapy with NIR lights (850 nm) into the brain as supplementary treatment to patients with glioblastoma. The main requirements are as follows:

1. Biocompatibility within physiological conditions
2. MRI/CT scan capability
3. Implantable device delivering a wavelength of 850 nm
4. Portable and minimalistic
5. Battery operated for efficient control

Approach

Research:
A large component of research was devoted to understanding what glioblastoma (GBM) is and how it is currently being treated. As the brain is one of the most important organs, it was essential that our device would not affect is normal functions. Photodynamic therapy (PDT) has been used in treatment in other cancers, primarily skin, so much of the already existing procedures were studied- as PDT has shown promise in early studies of the treatment of GBM. The metabolic pathway of the photosynthesizing drug, 5-aminolevulinic acid (5-ALA) was also studied to better understand how this therapy works.

Prototyping:
The physical and functional prototype was achieved after 2 iterations of designs. Comprised of a translucent polymethyl methacrylate (PMMA) polymer, this craniotomy implant was created from an original CAD file modeled after the average dimensions of a 3D-printed craniotomy implant accounting for skull thickness, curvature and tumor location. This part was then created using a CNC laser machine to ensure a uniform fit. 9 near-infrared (NIR) light bulbs were then recessed into the craniotomy implant that was cut, and wires were soldered to each light to provide a power source.

– Alpha prototype was created to provide a visualization of how large the parts needed to be and where they
were to be located in the body
– Beta prototype was created to test the transmittance of different NIR light sources, looking for one that
produces a high amount of wattage without potential overheating

The physical, functional model is comprised of a 12 x 17 x 9 mm PMMA piece with 9 NIR (850 nm) bulbs recessed into the piece. Each bulb was soldered together and cured with epoxy to prevent any dislocation of the light sources. These wires would then be connected to a battery in the chest cavity.

Testing:
Light penetration was collected through a calibrated diode to detect light waves at 850 nm. Transmittance was then calculated by comparing the maximum power output produced and the detected light through the PMMA. The data was then compared to literature to ensure similar outputs of transmittance and wattage. Temperature was also tested by using a NIR heat camera to ensure no significant physiological change occurs within the treatment time and implantation of the device.

Outcomes

– A final prototype was created that is biocompatible with physiological conditions, MRI/CT scan capable,
implantable delivering 850 nm light, portable and minimalistic and includes a battery for efficient control.
– The final prototype is a functioning device that is able to emit near infrared light, and is patient specific
– Polyether ether ketone (PEEK) is a colorless organic thermoplastic polymer that is also used for craniotomy
implants. Potentially, a new prototype could be created with this material
– In vitro/animal testing that shows how well this implantable device works and what future adjustments need
to be made