Reference #: KAT-1017-631447
Submit Date: 03/31/2002 18:30:41-0500

The new trial of PDT and PDD in the peripheral lung tumors

ABSTRACT:
PDT performed via a fiberoptic bronchoscope has been successful in treating early stage lung cancers involving the central airways. However, since 65% of lung cancers develop in the peripheral lung, fiberoptic bronchoscopic PDT is not suitable. Our recent experimental studies in animals at Tokyo Medical University Hospital, however, showed the feasibility of treating peripheral tumors with interstitial PDT developed via an optical fiber inserted into the tumor via a percutaneous needle. Based on these animal experiments, and with the approval of our institutional committee for ethical treatment, the authors performed PDT in patients. The possibility of photodynamic diagnosis of peripheral metastatic tumor with synchrotron radiation in mice was also investigated. PDT: We treated peripheral lung tumors in 8 patients in whom both surgery and radiotherapy were contraindicated. The primary objective of this study was to confirm necrosis of lung tumors induced by PDT and safety of this method. Cylindrical fibers delivering a diode laser (350 mW/cm2) with were inserted into the tumor under CT guidance. Partial response was obtained in 5 out of 8 patients without any severe side effects. Two patients suffered from pneumothorax, however both were easily treated by chest tube drainage. Photodynamic diagnosis (PDD) by synchrotron radiation: The authors investigated the possibility of detecting tiny solid tumors in the peripheral lung by photodynamic diagnostic procedure with Au-NPe6 photosensitization by synchrotron radiation. Tiny lesions approximately 1mm in diameter, were detected on the X-ray films of mice injected with cancer cells 5 hours after the injection of Au-NPe6. The X-ray images obtained before the Au-NPe6 injection showed no tumor shadow. The possibility of detecting tiny tumors by a parallel X-ray imaging system following injection of Au-NPe6 was recognized. Furthermore photosensitization by synchrotron radiation could have potential for photodynamic therapy of peripheral tumors in the lung.

Keywords: photodynamic therapy, photodynamic diagnosis, peripheral lung cancer, synchrotron radiation

Reference #: FIN-1019-676319
Submit Date: 04/24/2002 09:45:12-0500

Evaluation of drug dose, light dose, time between injection and light treatment, and fluence rate on tumor response and vascular damage after photodynamic therapy

ABSTRACT:
There are numerous variables that play a role in the biological effects that accompany photodynamic therapy (PDT). Among these are the amount of photosensitizer given to the subject, the amount of time allowed for the photosensitizer to accumulate in the target tissue, the total dose of light delivered and how quickly the light is delivered (fluence rate). As a goal to better understand how to effectively deliver phototherapy to patients, we varied each of these parameters for the photosensitizers Photofrin and Lutetium Texaphyrin (Lu-Tex). Endpoints for response were tumor control and changes within the microvasculature of tumor and surrounding skin. A new model was developed to allow us to examine tissue microvasculature over a period of 0-24 hours after light treatment. This allowed us to evaluate both the acute and chronic effects of phototherapy of the microvasculature or normal tissue and tumor. For animals given Photofrin, there was a fairly broad set of conditions that could be used to produce long term tumor destruction and vascular damage. Only certain conditions produced selective stasis of tumor microvasculature and this was a function of the time between drug injection and the total amount of photosensitizer delivered. The data suggests that certain serum levels of photosensitizer produce this effect since at low Photofrin dose, short injection intervals were needed to produce selectivity while at higher Photofrin dose, longer intervals only produced selectivity. These effects were mirrored by the tumor response experiments. For phototherapy with Lu-Tex, the variables to produce vascular damage and/or tumor destruction were considerably more confined that observed with Photofrin. Only certain drug/injection time/light dose and fluence combinations resulted in selective damage to tumor and to tumor microvasculature. Too much Lu-Tex or too short of an interval overwhelmed the process and too little drug, a long injection interval, or low fluence rate resulted in no response. We believe that these data will aid our clinical use of Photofrin and Lu-Tex and produce greater efficacy.

Keywords: Photodynamic therapy, Photofrin, Lutetium Texaphyrin, Vascular damage

Reference #: 095025
Submit Date:

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Reference #: WOO-1019-512503
Submit Date: 04/22/2002 16:45:38-0500

The potential use of photodynamic therapy in vascular diseases

ABSTRACT:
Photodynamic therapy for treatment of vascular lesions including de novo atherosclerosis and potentially restenosis, is an emerging clinical modality that is rapidly driven by recent advances in photosensitive drugs and light activation devices. Photobiology has been preclinically applied to an increasing number of cardiovascular indications. With conventional interventional tools there is a real risk of damage to the normal vessel wall while the hallmark of many photobiologic therapies is inherent selectivity. Nonclincial studies with many photosensitizers have demonstrated prevention of intimal hyperplasia and reduction in atheromatous plaque. Currently, two photosensitizers are undergoing clinical evaluation with many in preclinical testing. Here, preclinical, mechanism of action studies and the clinical viability of this emerging field will be discussed.

Keywords: PDT, plaque, restenosis

Reference #: HAS-1017-344860
Submit Date: 03/28/2002 13:37:25-0500

Photodynamic and Antiangiogenic Therapy : Local Control and Distant Metastasis

ABSTRACT:
Photodynamic Therapy (PDT) is emerging as a viable modality for local control of a variety of cancers and regulatory approvals worldwide have increased for its application to both neoplastic and non-neoplastic diseases. The PDT process involves the light activation of chemicals localized at the site of interest and therefore the major observable effects that have been studied the most have also been at and around the sites of illumination; in general these involved subcutaneous tumor models and were concentrated on tumor necrosis and growth/ regrowth parameters. A few studies have investigated orthotopic models and longterm effects such as survival and metastasis. However the photochemical process is a complex one and could start a cascade of events that have longterm consequences such as immune effects of PDT, induction of growth factors and distant metastasis. This presentation will focus on results from an investigaion on the relationship between local control of tumors by PDT and effects on distant metastasis as a function of various parameters in vivo.

Keywords: growth factors, prostate cancer, Lewis lung carcinoma, angiogenesis

Reference #: GOM-1016-500304
Submit Date: 03/18/2002 19:00:30-0500

Enhancing PDT with anti-angiogenic therapy

ABSTRACT:
Photodynamic therapy (PDT) induced cytotoxicity can involve direct tumor cell killing and vascular damage within the treated tumor tissue. In addition, a variety of oxidative and hypoxic stresses can occur during and after PDT. We have observed a myriad of pro-angiogenic molecules which are activated within tumors following PDT. These molecules include; transcription factors (HIF-1 alpha, NF kappa B, AP-1), growth factors (VEGF), proteases and enzymes (MMPs, COX-2), and cell surface receptors (integrins). We hypothesize that combining PDT with anti-angiogenic therapy may significantly improve the therapeutic responsiveness of PDT. Data will be presented using in-vivo murine tumor models demonstrating long-term improvement in tumor responses when PDT is combined with therapies which inhibit angiogenesis. The clinical significance of these results will be discussed.

Keywords: PDT, COX-2, VEGF, MMPs