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Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapy.

ABSTRACT: Photodynamic therapy (PDT) can lead to the creation of heterogeneous, response-limiting hypoxia during illumination, which may be controlled in part through illumination fluence rate. In the present report we consider (1) regional differences in hypoxia, vascular response, and cell kill as a function of tumor depth and (2) the role of fluence rate as a mediator of depth-dependent regional intratumor heterogeneity. Intradermal RIF murine tumors were treated with Photofrin PDT using surface illumination at an irradiance of 75 or 38 mW cm(-2). Regional heterogeneity in tumor response was examined through comparison of effects in the surface vs. base of tumors, i.e. along a plane parallel to the skin surface and perpendicular to the incident illumination. 75 mW cm(-2) PDT created significantly greater hypoxia in tumor bases relative to their surfaces. Increased hypoxia in the tumor base could not be attributed to regional differences in Photofrin concentration nor effects of fluence rate distribution on photochemical oxygen consumption, but significant depth-dependent heterogeneity in vascular responses and cytotoxic response were detected. At a lower fluence rate of 38 mW cm(-2), no detectable regional differences in hypoxia or cytotoxic responses were apparent, and heterogeneity in vascular response was significantly less than that during 75 mW cm(-2) PDT. This research suggests that the benefits of low-fluence-rate PDT are mediated in part by a reduction in intratumor heterogeneity in hypoxic, vascular and cytotoxic responses.

SUBMITTER: Busch TM

PROVIDER: S-EPMC2834171 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapy.

Busch Theresa M TM Xing Xiaoman X Yu Guoqiang G Yodh Arjun A Wileyto E Paul EP Wang Hsing-Wen HW Durduran Turgut T Zhu Timothy C TC Wang Ken Kang-Hsin KK

Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology 20091015 12

Photodynamic therapy (PDT) can lead to the creation of heterogeneous, response-limiting hypoxia during illumination, which may be controlled in part through illumination fluence rate. In the present report we consider (1) regional differences in hypoxia, vascular response, and cell kill as a function of tumor depth and (2) the role of fluence rate as a mediator of depth-dependent regional intratumor heterogeneity. Intradermal RIF murine tumors were treated with Photofrin PDT using surface illumi ...[more]

PMID: 20024165

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Project description:PurposeThis study evaluated changes in choroidal vascularity after half-fluence photodynamic therapy (HF-PDT) in patients with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (SS-OCT) en face imaging.MethodsThis retrospective comparative case series included 50 eyes of 25 patients with unilateral CSC who underwent HF-PDT and 50 age-and sex-matched normal healthy control eyes. En face SS-OCT images of the choriocapillaris, Sattler's layer, and Haller's layer were converted into binary images. The vascular proportions were defined as the percentage of the area of vascular lumen against the area of the 3.0-mm-diameter circular area. The main outcome measures were the vascular proportions before HF-PDT and at 6 weeks, 6 months, and 12 months after HF-PDT.ResultsAt baseline, the vascular proportions in the CSC eyes were significantly greater than those in the control eyes in all layers (choriocapillaris: 51.8% ± 15.5% vs. 41.3 ± 18.7%, P = 0.018; Sattler's: 58.6% ± 13.4% vs. 49.7% ± 15.7%, P = 0.017; Haller's: 65.3% ± 15.3% vs. 53.0% ± 13.4%, P = 0.001). In the CSC eyes, the vascular proportion in the choriocapillaris significantly decreased at 6 weeks (36.6% ± 16.9%, P < 0.001), 6 months (34.0% ± 12.3%, P < 0.001), and 12 months (34.8% ± 17.6%, P < 0.001) after HF-PDT compared with baseline. The vascular proportions in Sattler's and Haller's layers did not show a significant decrease at 6 weeks (Sattler's: 49.7% ± 17.3%, P = 0.052 and Haller's: 58.3% ± 12.9%, P = 0.558) but decreased significantly at 6 months (Sattler's: 48.9% ± 12.4%, P < 0.001 and Haller's: 57.7% ± 15.7%, P = 0.027) and 12 months after HF-PDT from the baseline values (Sattler's: 45.8% ± 10.4%, P < 0.001 and Haller's: 56.8% ± 15.7%, P < 0.001).ConclusionAfter HF-PDT, the choriocapillaris showed the earliest decrease in vascular proportion of en face images, Sattler's and Haller's layers showed later decreases. The temporal differences in the response of each layer may reflect the pathophysiology of CSC and the therapeutic mechanism of HF-PDT.

Dataset Information

Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapy.

Publications

Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapy.

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