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Optical modelling points the way to PDT progress

16 Apr 2009

Off-the-shelf commercial software is helping scientists to enhance the clinical efficacy of photodynamic therapy for targeted tumour destruction. Joe McEntee reports.

Photodynamic therapy (PDT) has been the "next big thing" in targeted cancer treatment for too long. Although clinical studies of the technique – which uses a light-activated drug to kill cancer cells – have often yielded dramatic tumour destruction without permanent damage to surrounding healthy tissue, the fact remains that PDT still has some way to go before it can be considered a mainstream treatment modality in the oncology clinic.

Among a posse of researchers looking for ways to fast-track progress are Claudio Sibata and his team at the Brody School of Medicine at East Carolina University (ECU) in Greenville, NC, US. One of the main thrusts of ECU's research is the development of robust software protocols and optical diagnostics for the planning and monitoring of the photodynamic treatment process. Ultimately, Sibata and his colleagues are hoping that their endeavours will yield big rewards in the shape of improved therapeutic outcomes and "personalized" PDT treatment regimes.

If the end-game is clear, then so too are the challenges that must be tackled along the way. Chao Sheng, an ECU researcher who specializes in optical modelling of PDT, highlights three parameters that complicate PDT dosimetry and treatment planning: the number of photons deposited in the target tissue; the concentration of photosensitizer that accumulates in the target tissue; and the local oxygen situation.

"All three parameters must be measured and quantified to optimize patient response," he told OLE. "Our research at ECU is focused on doing just that and developing a practical dosimetry model that will help clinicians to plan treatments according to the individual patient situation."

The mainstay of ECU's dosimetry modelling work is an off-the-shelf software package called the Advanced Systems Analysis Program (ASAP) BIO Toolkit from Breault Research Organization (BRO) in Tucson, AZ, US. One of the attractions of ASAP BIO is the software's integration of 3D models of the patient's organ geometry with models of light sources and tissue optical properties in a single package. "ASAP BIO is a powerful and modular software platform for running Monte Carlo simulations quickly," Sheng added. "I can easily define the target medium, light source and boundary conditions."

Right now, Sheng and his colleagues are using ASAP BIO to simulate the light dose deposited in tissue. Simulation, he explains, yields a number close to the actual photon energy dumped in the target tissue, which in turn determines the treatment outcome. "For example, if we have a laser with 100 mW/cm2 output and the tumour is 2_mm beneath skin, the actual light fluence rate received by the tumour will not be 100 mW/cm2. The deposited dose could be higher or lower – it depends on tissue optical properties, tissue geometry and other parameters. We can use ASAP to build up a model similar to the patient situation and calculate the optimum laser output to prevent over- or under-treatment."

Measurement science

The reference points for ECU's simulation work with ASAP BIO are provided by laboratory investigation – and more specifically, custom tools and methodologies to measure tissue optical properties (e.g. scattering coefficient and absorption coefficient) in vivo within a specified range of error. A case in point is a reflectance-based technique that uses a linear-array fibre-bundle probe to map a series of spatial reflectance values (sequentially measured by a spectrometer connected to a fibre-optic switch).

In parallel, the ECU team has developed a model that relates these reflectance profiles to optical properties of a turbid medium based on Monte Carlo simulations (using ASAP BIO) and tissue-phantom experiments. Preliminary results show good correlation between the known optical properties of the phantom and the measured optical properties, such that the system is now being used to study ex vivo bladder-tissue samples.

"Knowing the difference between the light dose delivered and the dose actually deposited in tissue will help physicians to minimize treatment outcome variation," noted Sheng. "In addition, the photosensitizer dose can also be derived from the change in tissue absorption coefficient before and after drug application."

Over time, Sheng is hopeful that ECU's refinement of ASAP BIO simulations will help to improve the clinical and commercial prospects of PDT technologies, though he cautions that improved therapeutic efficacy isn't a given. "Even if we fully understand the light dose and photosensitizer dose in tissue, the treatment outcome could still vary owing to different biological responses to the photochemical reactions. Nevertheless, our project, including the ASAP BIO simulations, will help to increase what we know about PDT mechanisms and also improve clinical planning."

Briefing: back to basics on PDT

PDT is a two-stage process that exploits the activation of a photosensitive drug by using light to destroy cancer cells.

In the first step, a photosensitizer is administered to the patient, either topically or via injection. After an appropriate time period, depending on the particular drug used and the targeted treatment area, much of the photosensitizer will have preferentially accumulated in the abnormal tissue.

The second stage is the irradiation of the tumour site with light of a wavelength that will be absorbed by the photosensitizer. Once activated, the drug produces cytotoxic singlet oxygen, which damages cellular membranes and causes cell death. By careful targeting of this light (most commonly provided by a laser), PDT selectively destroys abnormal tissue.

For more information about ASAP and to view bio-optics software demonstrations, visit www.breault.com/bio.

• This article originally appeared in the April 2009 issue of Optics & Laser Europe magazine.

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