American Society for Photobiology

ASP Conference 2016: 21-26 May 2016
Tampa Marriott Waterside Hotel & Marina


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4 - Frontiers in Clinical Photodiagnosis and Photodynamic Therapy

Florida 3   10:00 - 12:00

Chair(s): Chuck Simone
 
4-1   10:00  Photodiagnosis and Photodynamic Therapy: Can They Ever Be Combined In The Same Molecule? LG Arnaut*, University of Coimbra, Portugal ; MM Pereira, University of Coimbra, Portugal; JM Dabrowski, Jagiellonian University, Poland; FA Schaberle, Luzitin SA, Portugal; LB Rocha, Luzitin SA, Portugal; L Gomes-da-Silva, University of Coimbra, Portugal; MJF Calvete, University of Coimbra, Portugal; HT Soares, University of Coimbra, Portugal; AD Silva, University of Coimbra, Portugal; ACS Lobo, University of Coimbra, Portugal

Abstract: The new frontiers of cancer detection and treatment demand the visualization of diseased tissue with millimetric precision. Screening requires that diagnostic techniques are also affordable, portable and minimally invasive. Fluorescence imaging fulfills these requisites but requires fluorophores that target tumors with high NIR absorbance, intense fluorescence, large Stokes shifts, photostability and low toxicity. We disclose a deformed silicon phthalocyanine absorbing at 743 nm and emitting at 759 nm, and show that it accumulates in 4T1 cells implanted in a mammary gland of BALB/c mice. Fluorescence from 1 mm tumors was observed 30 min post-injection. PDT also benefits from sensitizers that target tumors, have high NIR absorbance and low photodecomposition, but they must also efficiently generate ROS. We have shown that a halogenated bacteriochlorin (named redaporfin) offered 86% cure rates of BALB/c mice bearing CT26 tumors. The phthalocyanine and redaporfin differ mostly in phototoxicity. Switching phototoxicity ON and OFF is discussed.

4-2   10:20  Repurposing Tetracyclines To Potentiate A Bi-Directionally Interactive Combination Of Photodynamic Therapy And Irinotecan For Cancer HC Huang*, Massachusetts General Hospital and Harvard Medical School ; I Rizvi, Massachusetts General Hospital and Harvard Medical School; J Liu, Massachusetts General Hospital and Harvard Medical School; T Hasan, Massachusetts General Hospital and Harvard Medical School

Abstract: It is becoming clear that the most effective treatments for complicated cancer will involve interactive regimens that target several non-overlapping pathways, preferably such that each component enhances the others to improve outcomes while minimizing side effects. Towards this goal, we developed a combination of photodynamic therapy (PDT) and irinotecan, where each component reinforces the others beyond their individual tumor destruction pathways, to synergistically reduce tumor burden and prolong animal survival. Furthermore, we repurposed FDA-approved tetracycline antibiotics, which have been shown to affect a range of targets in cancer, to overcome resistance that may render irinotecan treatment ineffective. This repurposing of FDA approved, non-cancer drugs presents an opportunity to design rapidly-translatable, mechanism-based therapies for cancer. The results will highlight insights into the cooperative effect of combination PDT and irinotecan, as well as the repurposed tetracyclines on the treatment response and molecular markers, in challenging mouse models of pancreatic and ovarian cancers.

4-3   10:40  Biomodulation of metabolic and signaling pathways to enhance photodynamic therapy efficacy for pancreatic adenocarcinoma and oral squamous cell carcinoma S Anbil*, Howard Hughes Medical Institute, Harvard Medical School ; I Rizvi, Harvard Medical School, Massachusetts General Hospital, Wellman Center for Photomedicine; Y Baglo, Harvard Medical School, Massachusetts General Hospital, Wellman Center for Photomedicine; M Broekgaarden, Harvard Medical School, Massachusetts General Hospital, Wellman Center for Photomedicine; E Maytin, Cleveland Clinic Lerner Research Institute; T Hasan, Harvard Medical School, Massachusetts General Hospital, Wellman Center for Photomedicine

Abstract: Vitamin based biomodulation of metabolic and paracrine-signaling pathways represents a promising approach to overcome tumor heterogeneity and poor treatment selectivity. Among these approaches includes biomodulation of the heme pathway with calcitriol to increase accumulation of protoporphryin IX (PpIX), the photosensitizer responsible for the cytotoxic effect of aminolevulinic acid (ALA)-based photodynamic therapy (PDT). Because cancer associated desmoplasia has been implicated in treatment resistance in several contexts, an opportunity exists to increase the susceptibility of these tumors to PDT through stromal rehabilitation while also improving the therapeutic index via heme pathway biomodulation. We investigate the ability of the vitamin hormones calcipotriol or retinoic acid to serve as dual-purpose biomodulatory and stromal reprogramming agents to enhance PDT efficacy in context of oral squamous cell carcinoma (OCa) and pancreatic ductal adenocarcinoma (PDA). OCa is highly prevalent in low resource settings where few feasible modalities exist for early detection and treatment. In contrast, PDA is frequently detected at late stage and characterized by a unique milieu comprising activated mesenchymal cells that facilitate tumor progression. Our approach has significance in both contexts: it may improve the theranostic potential of low-cost image guided PDT for OCa, and may enable synergy between PDT and other chemo/biologic therapies for PDA via modulation of tumorigenic signaling pathways. Using in-vitro and in-vivo approaches, we assess the ability of vitamin hormones to improve the selectivity and homogeneity of PpIX accumulation in OCa and PDA. In 2D and 3D cultures, we assess the ability of calcipotriol and retinoic-acid to induce quiescence in activated fibroblast lines, and assess the impacts of this "reprogramming" in PDA lines. A combined biomodulatory and reprogramming approach to improve PDT efficacy in PDA lines is tested.

4-4   11:00  Advances in Photodynamic Therapy for Thoracic Malignancies: Frontiers for Mesothelioma and Lung Cancer C Simone*, University of Pennsylvania

Abstract: Abstract not available.

4-5   11:20  Challenges of and Solution for Interstitial Photodynamic Therapy S Davis*, Thayer School of Engineering at Dartmouth

Abstract: Abstract not available.

4-6   11:40  Randomized Clinical Trial On The Efficacy And Safety Of UV-Free Blue Light For Treating Mild Psoriasis Vulgaris J Liebmann*, Philips GmbH, Innovative Technologies, Aachen, Germany ; M Born, Philips GmbH, Innovative Technologies, Aachen, Germany; S Pfaff, University Hospital, RWTH Aachen University, Aachen, Germany; V von Felbert, University Hospital, RWTH Aachen University, Aachen, Germany

Abstract: UV is used for phototherapy of different skin conditions like psoriasis. Though effective, it is carcinogenic making it a hazardous tool to treat skin diseases over longer periods of time. LED technology made it possible to investigate the effect of distinct wavelengths on human skin including the visible range. Here, UV-free blue light at 453nm reduces proliferation while inducing differentiation without causing toxicity in keratinocytes up to high fluences. Therefore, blue light could be a new treatment option for psoriasis - which is characterised by increased proliferation and disturbed differentiation of keratinocytes. The small size of LEDs enables the integration into compact and even wearable devices for localized treatment. We here present data from a randomized clinical trial using blue light for treating localized psoriasis plaques. We developed a wearable light device (453nm), delivering a fluence of 90J/cm² during 30 minutes of treatment for home use. We chose patients with two mirror plaques and randomized which plaque would be treated and which would be left untreated as a control. Patients were asked to treat the target plaque daily (at least 5 times / week) at home for an initiation treatment period of 4 weeks followed by a period of 8 weeks with 3 applications per week with at least one treatment free day in between treatments (maintenance treatment). After the last treatment (week 12) patients were followed up for 4 weeks without irradiation. The investigator assessed the local psoriasis severity index (LPSI) to evaluate treatment efficacy on study visits. The change from baseline (CfB) in LPSI, as primary endpoint, showed a significant improvement of the target plaques compared to the control plaques. So far no toxic or carcinogenic effects of blue light have been found. The patient compliance was high (97.87%) and no adverse events related to the blue light treatment or the use of the device were found. Satisfaction and usability of the blue light therapy was rated excellent on an average System Usability Scale (SUS) score by the patients.



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