![]() ![]() We have previously reported on the use of imaging techniques to evaluate the uptake and distribution of several photosensitizers in tumor tissue. However, no studies have yet examined the intratumor distribution of HPPH. They reported a 3:1 tumor-to-normal brain tissue ratio of HPPH concentration at 24 h post-administration with a half-life in tumor tissue of approximately 30 h. in a rat glioma model examined the tumor tissue selectivity for HPPH. This 10-fold lower plasma half-life is the primary reason for the reduced cutaneous photosensitivity associated with HPPH. These pharmacokinetic measurements have demonstrated that the half-life of HPPH in plasma is 20 - 26 h, which may be compared to the significantly longer elimination half-life of approximately 200 h with Photofrin. Īs drug biodistribution is an important component in determining treatment response and selectivity, several studies have evaluated pharmacokinetics of HPPH and its effectiveness in inducing tumor destruction with different drug-light intervals. Further, HPPH has demonstrated minimal skin photosensitization in preclinical and clinical studies. HPPH-PDT has demonstrated excellent safety and efficacy in the treatment of Barrett's esophagus, oral cavity cancers, and early and late stage esophageal and lung cancers. Among them, 2-2 devinyl pyropheophorbide-a (HPPH) has emerged as a promising candidate. In an effort to address this challenge, several next generation photosensitizers are being evaluated. Drawbacks posed by Photofrin include prolonged skin photosensitivity and limited tumor selectivity in patients. In the United States, FDA approval has been given to Porfimer sodium (Photofrin), a first-generation photosensitizer, for the treatment of Barrett's esophagus with high grade dysplasia, obstructing esophageal carcinoma and early and obstructing tracheobronchial carcinoma. Photodynamic therapy (PDT) continues to gain clinical acceptance worldwide as a minimally invasive treatment for neoplastic disease. Keywords: Photodynamic therapy, HPPH, In vivo imaging, Intratumor drug distribution, Confocal fluorescence microscopy, Immune cell imaging. Co-localization analysis reveals an increase in the fraction of Gr1 + cells expressing MHC-II, suggesting that HPPH-PDT is stimulating neutrophils to express an antigen-presenting phenotype. At 24 h post-PDT, an approximately 2-fold increase in MHC-II+ cells relative to untreated control is also observed. Dual color confocal imaging experiments demonstrates that about 90% of the anti-Gr1 cell population co-localized with anti-CD11b labeling, thus indicating that majority of the Gr1-labeled cells were neutrophils. Using IV-injected FITC-conjugated dextran as a fluorescent perfusion marker, we imaged tissue perfusion at different times post-irradiation and found that the reduced Gr1 + cell density at 48 h correlated strongly with functional damage to the vasculature as reported via decreased perfusion status. The maximum accumulation of Gr1 + cells is found at 24 h post-irradiation, followed by a decrease at the 48 h time-point. ![]() Imaging of the treated site at different time-points following irradiation shows significant and rapid increases in Gr1 + cells in response to therapy. Labeling of host cells using fluorophore-conjugated antibodies allowed the visualization of Gr1 +/CD11b + leukocytes and major histocompatibility complex class II (MHC-II) + cells in vivo. Confocal microscopy demonstrates a relatively homogeneous intratumor HPPH distribution. 24 h following intravenous (IV) administration of 1 μmol kg -1 HPPH, wide-field fluorescence imaging reveals tumor selectivity with an approximately 2-3-fold differential between tumor and adjacent normal tissue. We report the use of optical imaging strategies to noninvasively examine photosensitizer distribution and physiological and host responses to 2-2 devinyl pyropheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) of EMT6 tumors established in the ears of BALB/c mice. Select the file that you have just downloaded and select import option Reference Manager (RIS). Confocal Fluorescence Imaging Enables Noninvasive Quantitative Assessment of Host Cell Populations In Vivo Following Photodynamic Therapy. ![]()
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