21 Aug 2009
Fluorescence imaging can reveal a tumour's early biological response to photodynamic therapy.
The notoriously poor survival rate associated with pancreatic cancer has encouraged research into new treatment options. Photodynamic therapy (PDT) is a leading contender and trials are underway. However, conventional imaging-led methods of monitoring tumour growth are unable to provide the rapid response data that researchers are looking for.
A collaboration between Dartmouth College (Hanover, NH) and the Wellman Center for Photomedicine, Massachusetts General Hospital (Boston, MA), has now shown that fluorescence imaging can be combined with MRI to monitor the immediate effects of PDT in mouse models (Proc. SPIE 7380 73803M). It is hoped that this technique will reveal how PDT can be used most effectively against pancreatic cancer, possibly in partnership with drug or radiation therapy.
Structural imaging methods, such as MRI and CT, are often used to check whether a cancer treatment has halted tumour growth, induced shrinkage, or done nothing to stop the mass spreading. The problem is that these volume changes can take weeks to be seen on imaging, delaying important decisions on treatment management. This issue is particularly significant in fast-growing cancers, such as pancreatic adenocarcinoma.
Volume changes can also mask the biological effects of therapy. When the Dartmouth College researchers started looking at the effects of PDT on pancreatic cancer in mouse models using MRI alone, the tumours appeared to get larger immediately after treatment. But this size change was caused by inflammation, not cancer growth, engineering research associate Kimberley Samkoe told our sister website medicalphysicsweb.
The study team has now revised its follow-up protocol to include simultaneous fluorescence imaging, using a dedicated MR-coupled diffuse optical tomography system. "This means that we can take both the MR images and fluorescence tomography images at the same time," Samkoe said. "There is no need to realign the images afterwards because they have been taken at the same location."
The change requires that animals are injected with a fluorescent dye 48 hours before optical imaging. This dye is attached to epidermal growth factor (EGF), a protein that plays an important role in cell division. Pancreatic cancer cells contain particularly high numbers of EGF receptors (EGFR) so, after the dye has been injected, there should be more fluorescence from areas of active tumour than from surrounding tissue.
Early results from a study of tumour-bearing mice indicate that an early biological response to PDT can indeed be tracked using a combination of MRI and fluorescence imaging. EGF levels in treated mice are very low immediately after therapy, and only begin to increase again when the tumour starts to regrow, Samkoe said. This dual imaging strategy could potentially be used to tailor delivery of combination therapies involving PDT and anti-EGFR antibodies.
"We want to figure out if there is a time after PDT when these EGF receptors are very active. If we can deliver the antibody therapy at that point, then maybe we can further halt the regrowth of the tumour," Samkoe said.
Interpreting the optical data is far from straightforward because organs close to the pancreas may emit strong fluorescence signals too, Samkoe cautioned. For example, the normal intestine has high levels of EGF and is likely to fluoresce strongly, whilst the kidneys and the liver may contain large pools of labelled dye as part of the excretion process. "One of the biggest things right now is trying to sort out where the fluorescence is coming from and modelling that correctly," she said.