Toward Molecular Image-guidance for Intraoperative Breast Radiotherapy

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Copyright

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Purpose/Objective(s) 

Intra-operative radiation therapy (IORT) involves only a single fraction of radiation therapy and it is critical that the cancer margins be comprehensively treated. Currently, a standard method to visualize the remaining microscopic diseases after surgery does not exist. We are currently investigating a new technique, Radio-luminescence imaging, which utilizes molecularly-targeted nanophosphors to visualize residual disease. These nanoparticles emit optical light when irradiated, which can be detected by sensitive optical detectors; we have shown this imaging technique to be potentially more sensitive than positron emission tomography or fluorescence optical imaging. By localizing multiple molecular markers that are specific to a certain tumor, this technique would aid in treatment by providing feedback as to the extent of disease. This study demonstrates the sensitivity and ability of this technology in experimental phantoms and small-animal models, and outlines steps needed to translate this technique to the clinic.

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Materials/Methods 

Several experimental models were examined to test the performance and feasibility of this technique. We first investigated the sensitivity in phantoms loaded with phosphor and agar solution. We then determined the ability to recover multiple agents simultaneously by imaging phantoms with various concentrations of both BaYF4, doped with either Terbium (Tb) or Europium (Eu), which emit green and red light, respectively. We then imaged a small-animal model injected with both types of particles. All data was acquired with a diagnostic X-ray source for particle excitation, and a cooled-CCD coupled to a camera lens for imaging.

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Results 

The detection limit was determined to be sub-picomolar. The particles showed excellent linearity (correlation coefficient for both particles r > 0.99) with concentration. The results also show an excellent ability to separate the contributions from each phosphor, with coefficients of determination of R2 >0.91 for both sets of concentrations. The technical demonstration in a small animal model also showed excellent separation between the phosphors.

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Conclusions 

The results from this study demonstrate the ability of the proposed technique to provide a means to image multiple molecular markers simultaneously. Because of the low concentrations needed to resolve the phosphors, we estimate that we will be able to inject a reasonably low dose, which will still enable the resolution of multiple molecular contrasts.