Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth of necrosis in a murine tumor model

Cheung, R.; Solonenko, Michael; Busch, Theresa M.; Piero, Fábio Del; Putt, Mary; Hahn, Stephen M.; Yodh, Arjun G.

doi:10.1117/1.1560011

Cited by 36 publications

(29 citation statements)

References 20 publications

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“…2 and 4 show that there is a clear correlation between the measured quantities, indicating that deeper necrosis is achieved for larger decrease in the PS surface fluorescence. A previous study has been published by Cheung et al 23 presenting in vivo correlation of the PS fluorescence and the depth of necrosis. That study, however, is different from the present one, because in their case fluorescence was only measured before illumination as a way to quantify the amount of drug present in the tissue.…”

Section: Resultsmentioning

confidence: 99%

Possibility for a full optical determination of photodynamic therapy outcome

Vollet‐Filho¹,

Menezes²,

Moriyama³

et al. 2009

Journal of Applied Physics

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The microfluidic system for studies of carcinoma and normal cells interactions after photodynamic therapy (PDT) procedures Biomicrofluidics 5, 041101 (2011) Drug injection into fat tissue with a laser based microjet injector J. Appl. Phys. 109, 093105 (2011) A near infrared instrument to monitor relative hemoglobin concentrations of human bone tissue in vitro and in vivo Rev. Sci. Instrum. 81, 043111 (2010) Mechanism of oxidative stress generation in cells by localized near-infrared femtosecond laser excitation Appl. Phys. Lett. 95, 233702 (2009) Probing nanoantenna-directed photothermal destruction of tumors using noninvasive laser irradiation Appl. Phys. Lett. 95, 233701 (2009) Additional information on J. Appl. Phys. The efficacy of photodynamic therapy ͑PDT͒ depends on a variety of parameters: concentration of the photosensitizer at the time of treatment, light wavelength, fluence, fluence rate, availability of oxygen within the illuminated volume, and light distribution in the tissue. Dosimetry in PDT requires the congregation of adequate amounts of light, drug, and tissue oxygen. The adequate dosimetry should be able to predict the extension of the tissue damage. Photosensitizer photobleaching rate depends on the availability of molecular oxygen in the tissue. Based on photosensitizers photobleaching models, high photobleaching has to be associated with high production of singlet oxygen and therefore with higher photodynamic action, resulting in a greater depth of necrosis. The purpose of this work is to show a possible correlation between depth of necrosis and the in vivo photosensitizer ͑in this case, Photogem®͒ photodegradation during PDT. Such correlation allows possibilities for the development of a real time evaluation of the photodynamic action during PDT application. Experiments were performed in a range of fluence ͑0 -450 J / cm 2 ͒ at a constant fluence rate of 250 mW/ cm 2 and applying different illumination times ͑0-1800 s͒ to achieve the desired fluence. A quantity was defined ͑ ͒ as the product of fluorescence ratio ͑related to the photosensitizer degradation at the surface͒ and the observed depth of necrosis. The correlation between depth of necrosis and surface fluorescence signal is expressed in and could allow, in principle, a noninvasive monitoring of PDT effects during treatment. High degree of correlation is observed and a simple mathematical model to justify the results is presented.

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Section: Resultsmentioning

confidence: 99%

Possibility for a full optical determination of photodynamic therapy outcome

Vollet‐Filho¹,

Menezes²,

Moriyama³

et al. 2009

Journal of Applied Physics

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“…Studies have reported water concentration in tissue using near-infrared spectroscopy in the spectral range of 700 to 1100 nm (21,34,53). Photofrin concentration is easily extracted using fluorescence techniques (54), which are of interest, but not used in this study.…”

Section: Oxygen Measurement and Photodynamic Therapy Outcomementioning

confidence: 99%

Treatment-Induced Changes in Tumor Oxygenation Predict Photodynamic Therapy Outcome

Putt²,

et al. 2004

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Photodynamic therapy (PDT) requires oxygen to cause tumor damage, yet therapy itself can deplete or enhance tumor oxygenation. In the present work we measured the PDT-induced change in tumor oxygenation and explored its utility for predicting long-term response to treatment. The tissue hemoglobin oxygen saturation (SO 2 ) of murine tumors was noninvasively measured by broadband diffuse reflectance spectroscopy. In initial validation studies, the oxyhemoglobin dissociation curve for mouse blood was accurately recreated based on measurements during deoxygenation of a tissue phantom of mouse erythrocytes. In vivo studies exhibited excellent correlation between carbogen-induced changes in SO 2 and pO 2 of radiation-induced fibrosarcoma tumors measured by reflectance spectroscopy and the Eppendorf pO 2 histograph, respectively. In PDT studies radiation-induced fibrosarcoma tumor SO 2 was measured immediately before and after Photofrin-PDT (135 J/cm 2 , 38 mW/cm 2 ). Animals were subsequently followed for tumor growth to a volume of 400 mm 3 (time-to-400 mm 3 ) or the presence of tumor cure (no tumor growth at 90 days after treatment). In animals that recurred, the PDT-induced change in tumor SO 2 , i.e., relative-SO 2 (SO 2 after PDT/SO 2 before PDT) was positively correlated with treatment durability (time-to-400 mm 3 ). The predictive value of relative-SO 2 was confirmed in a second group of animals with enhanced pre-PDT oxygenation due to carbogen breathing. Furthermore, when all of the animals were considered (those that recurred and those that were cured) a highly significant association was found between increasing relative-SO 2 and increasing probability of survival, i.e., absence of recurrence. As independent variables, the SO 2 after PDT, the pre-PDT tumor volume, and light penetration depth all failed to predict response. As an independent variable, the SO 2 before PDT demonstrated a weak negative association with treatment durability; this association was driven by a correlation between decreasing pre-PDT SO 2 and increasing relative-SO 2 . These data suggest that monitoring of PDTinduced changes in tumor oxygenation may be a valuable prognostic indicator.

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“…Although Ps-PDT is no longer a first-line endoscopic treatment at our institution, we continue to work for improved treatment results by using Ps-PDT with optimized laser light dosimetry by measuring the light absorption and scattering properties of esophageal tissue and the actual drug levels and oxygen content in the mucosa in addition to the thickness of the esophageal wall. [43][44][45][46] The strength of our study is the comparison of large cohorts of patients treated with 3 different endoscopic treatments for BE neoplasia at the same center. The use of a comprehensive BE database included patients with all www.giejournal.org Volume -, No.…”

Section: Discussionmentioning

confidence: 99%