This PDF file contains the front matter associated with SPIE Proceedings volume 7551, including Title page, Copyright information, Table of Contents, Introduction (if any), and Conference Committee listing.

Two lines of evidence point to an early effect of photodamage on membrane trafficking. [1] Internalization of a fluorescent probe for hydrophobic membrane loci was impaired by prior photodamage. [2] Interference with the endocytic pathway by the PI-3 kinase antagonist wortmannin led to accumulation of cytoplasmic vacuoles suggesting a block in the recycling of plasma membrane components. Prior photodamage blocked this pathway so that no vacuoles were formed upon exposure of cells to wortmannin. In a murine hepatoma line, the endocytic pathway was preferentially sensitive to lysosomal photodamage. The role of photodamage to the endocytic pathway as a factor in PDT efficacy remains to be assessed.

The phthalocyanine photosensitizer Pc 4 binds preferentially to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components, including Bcl-2, are photodamaged and apoptosis is triggered. We recently prepared analogues of Pc 4 containing two axial ligands, one identical to the single ligand in Pc 4, and the other containing one or two hydroxyl groups on a dimethylsiloxy alkyl chain. Pc 181 is representative of this group of photosensitizers. In MCF-7 human breast cancer cells, the new analogues preferentially localized in lysosomes and were highly efficient in inducing apoptosis and overall cell death. The Bcl-2 family member Bid is required for signaling to mitochondria for apoptosis in response to primary lysosomal photodamage. To further evaluate the role of Bid, we compared the effects of PDT with Pc 4 or Pc 181 in wild-type murine embryonic fibroblasts and those knocked out for Bid. We find that the two cell lines are equally sensitive to killing by Pc 4-PDT, but the Bid^-/- cells are significantly more resistant to killing and apoptosis induction by Pc 181-PDT than are the Bid^+/+ cells. The data show that low levels of lysosomal photodamage are not alone lethal and that a specific defect in a factor required for apoptosis can severely compromise cell response to PDT.

Nanotechnology has the potential to deliver multiple imaging and therapeutic agents to the "right place at the right time". This could dramatically improve treatment responses in cancer which have been so far, dismal as well as allow us to monitor this response online. Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5% and there is a desperate need for effective treatments. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Here, we investigate the effect of neutralizing intracellular VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called "nanocells" in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies against cancer. Our studies demonstrate significant enhancement in treatment outcomes when nanocell-based PDT is combined with Avastin in orthotopic PanCa mouse models. We propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

Vitamin D3 (Vit D3) is a hormone essential for normal bone and cardiovascular health, and may participate in preventing nonmelanoma skin cancers (NMSC). Calcitriol (1,25 dihydroxyD3) is the active form of the hormone. We showed previously that calcitriol is a potent inducer of protoporphyrin IX (PpIX) in skin keratinocytes grown in organotypic cultures. Here, we investigated the ability of Vit D3 to enhance PpIX levels within skin tumors in vivo. Squamous tumors, generated by chemical carcinogenesis in mice, were pretreated for 3 days with topical calcitriol. Then 5-aminolevulinic acid (5-ALA) was applied topically, and PpIX levels were measured by noninvasive fluorimetry and in biopsied tissue. Calcitriol pretreatment resulted in a 3 to 4-fold elevation of PpIX in tumors, relative to no pretreatmen, providing significantly more photosensitizer available for tumor destruction. For deep tumors, topical calcitriol may not penetrate sufficiently. Therefore we explored whether systemic Vit D3, given short-term (3 days), might elevate PpIX within NMSC in a deep tumor model (subcutaneously-implanted A431 human squamous carcinoma cells). Defined amounts of calcitriol were injected into the mice for 3 d, followed by systemic 5-ALA, tissue biopsy, and confocal microscopic measurement of PpIX in frozen tissues. PpIX was clearly elevated after systemically delivered calcitriol. More work is needed, but if the amount of calcitriol required to elevate PpIX levels proves to be small, then the approach may ultimately prove attractive. Since most Americans are currently Vitamin D deficient, a small increase in calcitriol might be possible without risk of hypercalcemia.

For the fist time worldwide we report high amplitude NIR-Luminescence signals, measured in pig skin. The measurements are achieved with a recently developed setup that was shown to provide superior performance for ¹O₂- luminescence detection in vitro. This setup has been adapted to allow now the detection of singlet oxygen signals in vivo. Pig ears were used for first measurements as a widely accepted in vivo model for human skin.

We present the results of spectroscopic measurements of diffuse reflectance and fluorescence before and after photodynamic therapy of healthy canine peritoneal cavity. Animals were treated intra-operatively after iv injection of the benzoporphyrin derivative (BPD). The small bowel was treated using a uniform light field projected by a microlens-tipped fiber. The cavity was then filled with scattering medium and the remaining organs were treated using a moving diffuser. Diffuse reflectance and fluorescence measurements were made using a multi-fiber optical probe positioned on the surface of various tissues within the cavity before and after illumination. The measured data were analyzed to quantify hemoglobin concentration and oxygenation and sensitizer concentration.

To accurately calculate light fluence rate distribution in prostate photodynamic therapy (PDT), optical heterogeneity has to be taken into account. Previous study has shown that a kernel based on analytic solution of the diffusion equation can perform the calculation with accuracy comparable to Finite-element method. An assumption is made that light fluence rate detected at a point in the medium is affected primarily by the optical properties of points (or elements) on the line between the source and the point. The exponential decay term of the light fluence rate is expressed as an integral of effective attenuation coefficient of each point along the line. The kernel method is first developed for a point source and then extended for a linear source. A linear source is considered being composed of multiple point sources and light fluence rate is summation of the fluence rates generated by the point sources. In this study, we have implemented a fast ray-trace algorithm to substantially speed up the calculation. The kernel calculation is compared with FEM calculation and is examined with light fluence rate measurements. The examination with clinical measurement data shows that calculated fluence rates present similar features in distribution as the measurement, with errors of 30%-70% for the peak fluence rates. We concluded that our heterogeneous algorithm is potentially valuable for light fluence rate optimization during interstitial PDT.

Uniform light fluence distribution for patients undergoing photodynamic therapy (PDT) is critical to ensure predictable PDT outcome. However, common practice uses a point source to deliver light to the pleural cavity. To improve the uniformity of light fluence rate distribution, we have developed a treatment planning system using an infrared camera to track the movement of the point source. This study examines the light fluence (rate) delivered to chest phantom to simulate a patient undergoing pleural PDT. Fluence rate (mW/cm²) and cumulative fluence (J/cm²) was monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors were used for in-vivo light dosimetry. Light fluence rate in the pleural cavity is also calculated using the diffusion approximation with a finite-element model. We have established a correlation between the light fluence rate distribution and the light fluence rate measured on the selected points based on a spherical cavity model. Integrating sphere theory is used to aid the calculation of light fluence rate on the surface of the sphere as well as inside tissue assuming uniform optical properties. The resulting treatment planning tool can be valuable as a clinical guideline for future pleural PDT treatment.

Singlet oxygen (¹O₂) is the major cytotoxic agent for type II photodynamic therapy (PDT). The production of ¹O₂ involves the complex reactions among light, oxygen molecule, and photosensitizer. From universal macroscopic kinetic equations which describe the photochemical processes of PDT, the reacted ¹O₂ concentration, [¹O₂]_rx, with cell target can be expressed in a form related to time integration of the product of ¹O₂ quantum yield and the PDT dose rate. The object of this study is to develop optimization procedures that account for the optical heterogeneity of the patient prostate, the tissue photosensitizer concentrations, and tissue oxygenation, thereby enable delivery of uniform reacted singlet oxygen to the gland. We use the heterogeneous optical properties measured for a patient prostate to calculate a light fluence kernel. Several methods are used to optimize the positions and intensities of CDFs. The Cimmino feasibility algorithm, which is fast, linear, and always converges reliably, is applied as a search tool to optimize the weights of the light sources at each step of the iterative selection. Maximum and minimum dose limits chosen for sample points in the prostate constrain the solution for the intensities of the linear light sources. The study shows that optimization of individual light source positions and intensities is feasible for the heterogeneous prostate during PDT. To study how different photosensitizer distributions as well as tissue oxygenation in the prostate affect optimization, comparisons of light fluence rate were made with measured distribution of photosensitizer in prostate under different tissue oxygenation conditions.

Photodynamic therapy (PDT) is a light activated chemotherapy that is dependent on three parameters: photosensitizer (PS) concentration; oxygen concentration; and light dosage. Due to highly variable treatment response, the development of an accurate dosimeter to optimize PDT treatment outcome is an important requirement for practical applications. Singlet oxygen is an active species in PDT, and we are developing two instruments, an ultra-sensitive singlet oxygen point sensor and a 2D imager, with the goal of a real-time dosimeter for PDT researchers. The 2D imaging system can visualize spatial maps of both the singlet oxygen production and the location of the PS in a tumor during PDT. We have detected the production of singlet oxygen during PDT treatments with both in-vitro and in-vivo studies. Effects of photobleaching have also been observed. These results are promising for the development of the sensor as a real-time dosimeter for PDT which would be a valuable tool for PDT research and could lead to more effective treatment outcome. We summarize recent results in this paper.

Mitochondria are the power house of living cells, where the synthesis of the chemical "energy currency" adenosine triphosphate (ATP) occurs. Oxidative phosphorylation by a series of membrane protein complexes I to IV, that is, the electron transport chain, is the source of the electrochemical potential difference or proton motive force (PMF) of protons across the inner mitochondrial membrane. The PMF is required for ATP production by complex V of the electron transport chain, i.e. by F_oF₁-ATP synthase. Destroying cytochrome C oxidase (COX; complex IV) in Photodynamic Therapy (PDT) is achieved by the cationic photosensitizer Pt(II)-TMPyP. Electron microscopy revealed the disruption of the mitochondrial christae as a primary step of PDT. Time resolved phosphorescence measurements identified COX as the binding site for Pt(II)-TMPyP in living HeLa cells. As this photosensitizer competed with cytochrome C in binding to COX, destruction of COX might not only disturb ATP synthesis but could expedite the release of cytochrome C to the cytosol inducing apoptosis.

We introduce a new platform to study treatment response in adherent micrometastatic ovarian cancer, combining an in vitro 3D model, with custom quantitative analysis routines to report growth and cytotoxic response in large sets of image data. OVCAR-5 human ovarian cancer cells were grown on a bed of Growth Factor Reduced Matrigel^TM (GFR Matrigel^TM). Using batch analysis routines to analyze longitudinal image data we show that in vitro tumor growth leads to a reproducible log-normal size distribution with two well-defined peaks. These distinct growth modes correspond to a population with approximately constant diameter of 20μm over the time probed, while the other peak corresponds to a more rapidly assembling sub-distribution of micronodules which shifts towards larger peak center positions with mean equivalent diameters of 92μm, 120μm and 150μm at days 7, 10 and 17 following plating. At day 10, 3D and monolayer cultures were treated with a regimen of either carboplatin or photodynamic therapy. Using a quantitative fluorescence imaging approach we report dose response curves and demonstrate that 3D nodules are significantly less sensitive to treatment than the same cells grown in monolayer. 3D cultures subject to 5J/cm² PDT (250nM BPD-MA) exhibited a mean viability of 80% (95% CI = 73% to 82%) relative to no treatment control. 3D cultures subject to carboplatin treatment at 100μM concentration exhibited a mean viability of 92% (95% CI =86% to 97%). A combination treatment of 5J/cm² PDT followed by 100μM carboplatin yielded an enhanced cytotoxic effect with mean viability of 46%, 95% confidence interval (CI) = (35 % to 46%).

Ovarian epithelial cancer has a high morbidity due to its propensity to metastasize onto surfaces in the abdomen. In order to effectively treat these metastatic lesions with photodynamic therapy (PDT), it is critical to understand the detailed dynamics of the PDT response. 3D in vitro models of ovarian cancer are a promising system for studying the response to PDT of these lesions, as they replicate the size, appearance, and characteristics of metastatic disease observed in the clinic. An ideal approach capable of non-purturbative, 3D imaging of this model is optical coherence tomography (OCT). An ultrahigh resolution time-lapse OCT (TL-OCT) system was used to visualize the photodynamic therapeutic response in the hours and days following treatment. Tumor nodules were observed to experience rapid cell death within the first 24 hours post-treatment using benzophorphyrin derivative monoacid A (BPD), characterized by structural breakdown of the model nodules. Highly scattering bodies were observed with OCT contrast to form at the periphery of the tumor nodules. These highly scattering moieties were identified as apoptotic bodies, indicating that OCT is capable of tracking the PDT-induced apoptosis in real-time without the need for labels.

Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

We report on some of the optical properties of hematoporphyrin monomethyl ether (HMME), a relatively new photosensitizer that has been in clinical trials in China since the early 1990s. We characterized the photosensitizer on the basis of one photon absorption and emission. In addition, the effects of photobleaching were probed to characterize its decay kinetics.

Verteporfin photodynamic therapy (PDT) is a promising adjuvant therapy for pancreas cancer and investigations for its use are currently underway in both orthotopic xenograft mouse models and in human clinical trials. The mouse models have been studied extensively using magnetic resonance (MR) imaging as a measure of surrogate response to verteporfin PDT and it was found that tumor lines with different levels of aggression respond with varying levels to PDT. MR imaging was successful in determining the necrotic volume caused by PDT but there was difficultly in distinguishing inflamed tissues and regions of surviving tumor. In order to understand the molecular changes within the tumor immediately post-PDT we propose the implementation of MR-guided fluorescence molecular tomography (FMT) in conjunction with an exogenously administered fluorescently labeled epidermal growth factor (EGF-IRDye800CW, LI-COR Biosciences). We have previously shown that MR-guided FMT is feasible in the mouse abdomen when multiple regions of fluorescence are considered from contributing internal organs. In this case the highly aggressive AsPC-1 (+EGFR) orthotopic tumor was implanted in SCID mice, interstitial verteporfin PDT (1mg/kg, 20J/cm) was performed when the tumor reached ~60mm³ and both tumor volume and EGF binding were followed with MR-guided FMT.

Photodynamic therapy of tumors involving Type 2 photosenstizers has been conspicuously successful, but the Type 1 process, in contrast, has not received much attention despite its considerable potential. Accordingly, several classes of molecules containing fragile bonds such as azido (-N=N=N), azo (-N=N-), and oxaza (-N-O-) functional groups that produce reactive intermediates such as radicals and nitrenes upon photoexcitation with visible light were prepared and tested for cell viability using U397 leukemia cell line. The cells were incubated with the photosensitizer at various concentrations, and were illuminated for 5, 10, and 20 minutes. The results show that all the photosensitizers caused cell death compared to the controls when exposed to both the photosensitizers and light.

Photodynamic therapy involving Type 2 photosenstizers has been conspicuously successful in the treatment of various lesions. Type 1 process, in contrast has not received much attention despite its considerable potential. We have prepared several classes of molecules containing fragile bonds that will produce reactive intermediates such as radicals and nitrenes upon photoexcitation with UV-A and visible light. In a primary screen, many of these compounds had a significant concentration and light dose dependent effect on the cell viability on U937. The chemistry of these compounds differentiated their ability to induced cytotoxic effects. To further establish these findings, we tested one compound representing each class of chemistry in three different tumor cell lines. Cells were incubated with three different concentrations (100μM, 25μM and 6.25μM) and exposed to UV light dose of 4J/cm² and 8J/cm². The compounds showed varying effects on viability in different cell lines. Finally we also investigated the ability to induce apoptosis as the mechanism of cell death in HCT116 cell lines using the experimental conditions mentioned. The type 1 photosensitizers induced apoptosis as early as 4 hours after exposure in HCT116 cells and the rate of apoptosis increased with time with majority of cells in late apoptotic or necrotic stage.

Objective: In in vitro photodynamic therapy, the LD50 of Pc 181 has been reported to be 7 to 8 times less than that of silicon phthalocyanine 4 (Pc 4). The Optical Pharmacokinetic System (OPS) can measure photosensitizer concentrations in accessible tissues non-invasively. We used OPS to evaluate the tumor pharmacokinetics of Pc 181 and Pc 4 and the tissue drug distribution in SCID mice bearing either human breast cancer MDA-MB-231 or human head and neck squamous cell carcinoma SCC-15 xenografts. Methods: Following iv administration of 2.5 mg/kg Pc 181 or 2 mg/kg Pc 4 to SCID mice, OPS measurements were taken on tumor and normal tissues between 5 and 4320 min in vivo or in situ. Results: Large variations in tumor Pc 181 concentrations were observed among mice. In MDA-MB-231 tumors, the Pc 181 concentration peaked at 240 min, and was retained in the tumor. Tumor Pc 181 concentrations were much less than the tumor Pc 4 concentrations at an equimolar dose. Pc 181 concentrations were the highest in liver, followed by spleen, and kidney. In mice bearing SCC-15 xenografts, skin and underlying tissue Pc 181 concentrations were higher than tumor concentrations at all time points examined. Conclusions: This first Pc 181 pharmacokinetics study described a tissue Pc 181 distribution similar to that of Pc 4. However, tumor Pc 181 concentrations were lower than those of Pc 4 at equimolar doses.

Control of infection in wounds is critically important to avoid transition to sepsis; however, recent rise of drug-resistant bacteria makes it difficult. Thus, antimicrobial photodynamic therapy (APDT) has recently received considerable attention. In this study, we examined methylene blue (MB)-mediated photodynamic inactivation of Psuedomonas aeruginosa in rat burned skin. Two days after infection, the wound surface was contacted with a MB solution at different concentrations, and thereafter the wound was irradiated with cw 665-nm light at a constant power density of 250 mW/cm² for different time durations. We obtained a two orders of magnitude decrease in the number of bacteria by PDT with a 2-h contact of 0.5-mM MB solution and a illumination of 480 J/cm², demonstrating the efficacy of PDT against infection with Ps. aeruginosa in burns.

The treatment of superficial skin cancers with photodynamic therapy (PDT) relies on uniformly covering the treatment target with sufficient light fluence using an externally applied source. Incorporating an integrating sphere into the treatment procedure makes this easier to achieve. A prototype sphere was characterized using a 1% Intralipid phantom with various concentrations of India ink. Profile and depth fluence measurements were taken in the phantom with and without the sphere in place. The sphere was effective at increasing the fluence rate by up to 100% and at improving the uniformity and penumbra of the beam for all India ink concentrations. The relative increase in fluence was lower for the higher concentrations of ink. These findings were supported by Monte Carlo simulations. Additional Monte Carlo simulations investigated the relationship between the sphere parameters and the beam characteristics. Beam flatness improved with an increase in overlap of the incident beam on the sphere wall; however the fluence increase was not as large.

A large-size blanket composed of the parallel catheters and silica core side glowing fiber is designed to substitute the hand-held point source in the photodynamic therapy treatment (PDT) of the malignant pleural or intraperitoneal diseases. It produces a reasonably uniform field for effective light coverage and is flexible to conform to anatomic structures in intraoperative PDT. The size of the blanket is 30cm×20cm. The light blanket composed of several PVC layers and a series of parallel catheters attached on both sides of the intralipid layer of 0.2% concentration. On one side of the intralipid layer, the parallel fiber catheters were attached using thermal sealing technique. On the other side, the parallel detect catheters were attached along the perpendicular direction. 0.1mm aluminum foil was used to construct the reflection layer to enhance the efficiency of light delivery. The long single side-glowing fiber goes through the fiber catheters according to the specific fiber pattern design. Compared with the prototype of the first generation, the new design is more cost-efficient and more applicable for clinical applications. The light distribution of the blanket was characterized by scanning experiments which were performed in flatness and on the curved surface of tissue body phantom. The fluence rate generated by the blanket can meet requirements for the light delivery in pleural or intraperitoneal (IP) PDT. Taking the advantage of large coverage and flexible conformity, it has great value to increase the reliability and consistency of PDT.

We investigated experimentally dependence of light fluence on treated depth with photosensitization reaction shortly after photosensitizer injection in rabbit myocardial tissue in vivo. In this particular photosensitization reaction scheme, the photosensitizer accumulation characteristics for target region are not available. Meanwhile, the photosensitizer dose and hospitalization period under restricted light circumstance might be reduced. Since both photosensitizer and oxygen supply are governed by blood flow, this photosensitization reaction is influenced significantly by blood flow variation in particular blood vessel occlusion. We employed the myocardial tissue to keep tissue blood flow during the photosensitization reaction because vessel blood flow speed in myocardial tissue is fast to resist vascular occlusion. Surgically exposed rabbits myocardial tissues were irradiated with the light fluence ranging 25-100 J/cm² by a 663 nm diode laser 30 min after the injection of 2 mg/kg water soluble chlorin photosensitizer, Talaporfin sodium. Two weeks after the irradiation, the rabbits were sacrificed and the histological specimens of the irradiated area were made to measure scar layer thickness. The scar layer tissue thickness of 0.2-3.0 mm was observed microscopically by the light fluence ranging 25-100 J/cm². The scarring threshold in the deposit light fluence was estimated to 15-25 J/cm³ based on the above mentioned relation assuming constant and uniform myocardial effective attenuation coefficient of 0.72 mm^-1. The estimated scarring threshold in the deposit light fluence was lower than the threshold of conventional PDT. Large variation of the estimated threshold value might be attributed to unconsidered PDT parameter such as flow rate inhomogeneity in the myocardial tissue. These results suggested that the photosensitization reaction investigated in this study would be available to apply arrhythmia therapy such as atrial fibrillation.

This study examines the light fluence (rate) delivered to patients undergoing pleural PDT as a function of treatment time, treatment volume and surface area. The accuracy of treatment delivery is analyzed as a function of the calibration accuracies of each isotropic detector and the calibration integrating sphere. The patients studied here are enrolled in a Phase I clinical trial of HPPH-mediated PDT for the treatment of non-small cell lung cancer with pleural effusion. Patients are administered 4mg per kg body weight HPPH 24-48 hours before the surgery. Patients undergoing photodynamic therapy (PDT) are treated with light therapy with a fluence of 15-60 J/cm² at 661nm. Fluence rate (mW/cm²) and cumulative fluence (J/cm²) is monitored at 7 different sites during the entire light treatment delivery. Isotropic detectors are used for in-vivo light dosimetry. The anisotropy of each isotropic detector was found to be within 15%. The mean fluence rate delivery and treatment time are recorded. A correlation between the treatment time and the treatment volume is established. The result can be used as a clinical guideline for future pleural PDT treatment.

Photodynamic therapy (PDT) mediated with Verteporfin is being investigated as a pancreatic cancer treatment in the cases for non-surgical candidates. Tissue response to PDT is based on a number of parameters including photosensitizer (PS) dose, light dose and time interval between light application and PS injection. In this study, PS uptake and distribution in animal leg muscle, oral cavity tissues, pancreas and tumor was measured in vivo using light-induced fluorescence spectroscopy (LIFS) via an Aurora Optics Inc. PDT fluorescence dosimeter. An orthotopic pancreatic cancer model (AsPC-1) was implanted in SCID mice and treated with the PS. Probe measurements were made using a surface probe and an interstitial needle probe before and up to one hour after intravenous tail vein injection of the PS. The study demonstrated that it is possible to correlate in-vivo LIFS measurements of the PS uptake in the pancreas with measurements taken from the oral cavity indicating that light dosimetry of PDT of the pancreas can be ascertained from the LIFS measurements in the oral cavity. These results emphasize the importance of light dosimetry in improving the therapeutic outcome of PDT through light dose adaptation to the relative in situ tissue PS concentration.

Delivery of therapeutic agents to solid tumors is challenging, and the issues that govern this can be distilled down into parameters which allow computational modeling. In this paper, the basic rate equations and diffusion kernel for the time and space modeling of delivery are developed, along with an analytical solution to this equation. The model is then used to compare delivery of Avastin antibody relative to delivery encapsulated in a nanocell delivery vehicle. The key factors are the plasma clearance or excretion rates, and the binding, or not, as it transports into the tumor tissue. A reduction in the plasma clearance rate inherently increases available delivery over time, and additionally the reduction in binding from antibody to nanocell allows higher penetration into the tumor at the longer circulation times.

In Taiwan, oral cancer has become a prominent cancer because of its highest annual increase rate among all cancer diseases. Betel quid chewing habit is a major risk factor for oral precancerous and cancerous lesions and there are more than two million people who have this habit in Taiwan. Our previous studies showed that chlorophyll-pheophytin derivative (CPD)-mediated PDT is very effective for killing of SCC-4 cell lines in vitro. In order to decrease the systemic phototoxic effect of CPD, this study was designed to use a topical CPD-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions of moderate to severe dysplasia were induced and proven by histological examination. These induced precancerous lesions were used for testing the efficacy of topical CPD-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when CPD reached its peak level in the lesional epithelial cells after topical application of CPD gel. We found that CPD reached its peak level in precancerous lesions about 1 hour (range, 0 to 30 hours) after topical application of CPD gel. The precancerous lesions in hamsters were then treated with topical CPD-mediated PDT (fluence rate: 200 mW/cm²; light exposure dose 100 J/cm²) using the portable WonderLight LED 635 nm fiber-guided light device once or twice a week. Visual and histological examination demonstrated that topical CPD-mediated PDT was partially effective treatment modality for DMBA-induced hamster buccal pouch precancerous lesions.