Abstract
BackgroundPhotosensitizer based fluorescence imaging and spectroscopy is fast becoming a promising approach for cancer detection. The purpose of this study was to examine the use of the photosensitizer chlorin e6 (Ce6) formulated in polyvinylpyrrolidone (PVP) as a potential exogenous fluorophore for fluorescence imaging and spectroscopic detection of human cancer tissue xenografted in preclinical models as well as in a patient.MethodsFluorescence imaging was performed on MGH human bladder tumor xenografted on both the chick chorioallantoic membrane (CAM) and the murine model using a fluorescence endoscopy imaging system. In addition, fiber optic based fluorescence spectroscopy was performed on tumors and various normal organs in the same mice to validate the macroscopic images. In one patient, fluorescence imaging was performed on angiosarcoma lesions and normal skin in conjunction with fluorescence spectroscopy to validate Ce6-PVP induced fluorescence visual assessment of the lesions.ResultsMargins of tumor xenografts in the CAM model were clearly outlined under fluorescence imaging. Ce6-PVP-induced fluorescence imaging yielded a specificity of 83% on the CAM model. In mice, fluorescence intensity of Ce6-PVP was higher in bladder tumor compared to adjacent muscle and normal bladder. Clinical results confirmed that fluorescence imaging clearly captured the fluorescence of Ce6-PVP in angiosarcoma lesions and good correlation was found between fluorescence imaging and spectral measurement in the patient.ConclusionCombination of Ce6-PVP induced fluorescence imaging and spectroscopy could allow for optical detection and discrimination between cancer and the surrounding normal tissues. Ce6-PVP seems to be a promising fluorophore for fluorescence diagnosis of cancer.
Highlights
Photosensitizer based fluorescence imaging and spectroscopy is fast becoming a promising approach for cancer detection
Fluorescence imaging of bladder tumor xenografts on the chorioallantoic membrane (CAM) model Fluorescence was not observed from the tumors under blue light illumination before drug administration
Fluorescence in the normal CAM tissue was lower compared to fluorescence in the tumor tissue, suggesting either a lower uptake or faster clearance rate from normal tissue of the CAM (Figure 1)
Summary
Photosensitizer based fluorescence imaging and spectroscopy is fast becoming a promising approach for cancer detection. Random surveillance biopsies are the existing gold standard for the identification of lesions in pre-neoplastic conditions This method is prone to sampling error, time-consuming, subjective and cost-inefficient. A variety of optical techniques have recently been utilized for the diagnostic study of cancerous tissue These include fluorescence spectroscopy [1], Raman spectroscopy [2], light scattering spectroscopy [3], and Fourier-transform infrared spectroscopy [4]. These optical spectroscopic techniques are capable of providing biochemical and morphological information in short integration times, which can be used for automated diagnosis of intact tissue. In order to be useful as a comprehensive screening procedure, the optical technique must allow rapid real time imaging of a large area of tissue rather than point by point measurement, such that suspicious regions could be identified accurately and biopsied for histopathologic correlation [5]
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