Background and Objective: Patients with high grade dysplasia (HGD) in Barrett's esophagus are at a high risk for developing esophageal adenocarcinoma. Esophagectomy is the standard treatment for such patients. The objective of this study was to evaluate the safety and efficacy of photodynamic therapy (PDT) using an improved light delivery balloon for ablation of Barrett's esophagus with high grade dysplasia and/or early cancer. Materials and Methods: 20 patients with HGD or early cancer (19 with HGD, 1 with T1 cancer) received 2 mg/kg of porfimer sodium, intravenously. Two to three days after the injection, laser light was delivered using a cylindrical diffuser inserted inside a 20-mm diameter reflective esophageal PDT balloon. Initially, the balloon was inflated to a pressure of 80 mm Hg. The balloon pressure was gradually reduced to 30 mm Hg. A KTP/dye laser at 630 nm was used as the light source. Light dose of 115 J/cm was delivered at an intensity of 270 mw/cm. Nodules were pre- treated with an extra 50 J/cm using a short diffuser inserted through the scope. Patients were maintained on PPI therapy to keep the gastric pH higher than 4. Eighteen patients required one treatment, while two patients were treated twice. Follow-up consisted of endoscopy with four quadrant biopsies at every 2 cm of the treated area. Thermal ablation was used to treat small residual islands on the follow-ups. The follow-up endoscopies ranged from 6 to 17 months. Results: On follow-up endoscopy, 12 patients had complete replacement of their Barrett's mucosa with neosquamous mucosa. Five patients had residual non-dysplastic Barrett's mucosa, one had indefinite dysplasia, two had low grad dysplasia. There were no residual HGD or cancers. The average length of Barrett's was reduced from 5.4 cm to 1.2 cm. High balloon pressure resulted in wide variation in PDT response among patients. Lower balloon pressures resulted in more consistent destruction of Barrett's mucosa among patients. Five patients developed strictures which responded well to dilations. One patient developed atrial fibrillation which responded to medications. Conclusions: Photodynamic therapy using a 20 mm diameter balloon was effective for ablation of high grade dysplasia and early cancer in Barrett's esophagus. Low balloon inflation pressure was a critical parameter in producing consistent tissue destruction.

A major limitation of PDT for Barrett's esophagus is the development of esophageal strictures. This report summarizes the effects of PDT delivered to mouse esophagus. Sixty-two C3H/Nsd mice were injected with Photofrin (2-10mg/Kg) intraperitoneally. Forty-eight hours later a 1 cm laser probe was passed orally to the mid-esophagus. Light energy (630nm) ranged from 0 to 400 Joules/cm (J). Animals were sacrificed if death was imminent, otherwise at 6 weeks and 3 months. Gross and microscopic exams were performed on paraffin embedded esophagus and lung specimens. Exposure to 400J as a single fraction, 125 X 3 or 150 X 3 fractions resulted in a lethal pulmonary injury in 90% of mice within 48 hours. There was no esophageal mucosal damage at this early time point. Lower doses caused minor pulmonary injury allowing long-term survival but no change in the esophageal endothelium and no stricture. In the mouse, this histopathologic study demonstrates that pulmonary toxicity is the limiting factor following esophageal PDT. At lower PDT doses, minimal pulmonary damage occurred but no effect was observed on the esophagus. We believe the 5 mm depth of PDT injury leads to lethal pulmonary damage preventing subsequent study of the effects on the esophagus.

Photodynamic therapy (PDT) utilizes optical energy to activate a pre-administered photosensitizer drug to achieve a localized tumor control. In the presented study, PDT mediated with a second-generation photosensitizer, WST09 (TOOKAD, Steba Biotech, The Netherlands), is investigated as an alternative therapy in the treatment of prostate cancer. In vivo canine prostate is used as the animal model. PDT was performed by irradiating the surgically exposed prostates both superficially and interstitially with a diode laser (763 nm) to activate the intra-operatively i.v. infused photosensitizer. During light irradiation, tissue optical properties, and temperature were monitored. During the one-week to 3-month period post PDT treatment, the dogs recovered well with little or no complications. The prostates were harvested and subjected to histopathological evaluations. Maximum lesion size of over 3 cm in dimension could be achieved with a single treatment, suggesting the therapy is extremely effective in destroying prostatic tissue. Although we found there was loss of epithelial lining in prostatic urethra, there was no evidence it had caused urinary tract side effects as reported in those studies utilizing transurethral irradiation. In conclusion, we found second generation photosensitizer WST09 mediated PDT may provide an excellent alternative to treat prostate cancer.

Photodynamic Therapy (PDT) and fluorescent diagnostics (FD) using photosensitizers Photosense (Aluminium Phtalocyanine, (NIOPIC, Russia)(PS) and Alasense have been provided in 101 patients with breast cancer as a multicenter study. All patients had recurrences of breast cancer (skin metastases) after combined treatment, chemotherapy and radiotherapy. FD of tumor with detecting of subclinical sites, accumulation of PS in tumor, adjacent tissue, skin before and during PDT was fulfilled. Multiple surface irradiations were carried on with interval 24-72 hours (semiconductive laser - (lambda) =672+2nm) in light does 100J/cm² and total light does 300-900 J/cm². 2 months after PDT we had overall response rate of 86,87% with complete response (CR) in 51,48% and partial response in 35,39%. During year after PDT in 52 patients with CR we had CR in 36,6% local recurrences in 23,1%, progression (distant (lung or bone) metastasis) in 40,4% of cases. Our experience show pronounced efficacy of PDT for skin metastases of breast cancer.

In our previous phase II studies we treated 112 patients with malignant brain tumors with 2-mg/kg Photofrin i.v. and intra-operative cavitary PDT. We concluded that PDT was safe in patients with newly diagnosed or recurrent supratentorial malignant gliomas. Pathology, performance grade and light dose were significantly related to survival time. In selected patients when an adequate light dose was used survival time improved. The surgical mortality rate was less than 3%. [spie 2000] We have initiated two randomized prospective trials - the first, to determine if the addition of PDT to standard therapy [surgery, radiation and/or chemotherapy] prolongs the survival of patients with newly diagnosed malignant astrocytic tumors; and the second, to determine whether high light dose PDT [120 J/cm²] is superior to low light dose PDT [40 J/cm²] in patients with recurrent malignant astrocytic tumors. To date, 158 patients have been recruited - 72 to the newly diagnosed malignant glioma study and 86 to the recurrent glioma study. In the recurrent glioma study we compared the pre-operative KS and elements of the neurological examination [speech function, visual fields, cognitive function, sensory examination and gait] to the post-operative examinations at hospital discharge. The means were compared by paired student-t test. The KS in 86 of 88 patients with recurrent gliomas were assessable. The mean [s.d.] preoperative and post-operative KS were 82+/- 14 and 79+/- 17, respectively [p=0.003]. The mean decline in KS, although statistically significant, was small and of no clinical importance. The median Karnofsky score changed from 90 to 80. The KS improved in 8 patients; their post-operative average length of stay (alos) was =9.7 days. There was no change in 47 [alos=8.3], a decline of 10 points in 24 [aloc=13.4] and declined by more than 10 points in 7 [alos=23.3]. Three of these 7 patients who had a decline of >10 points improved in follow-up but did not reach their preoperative KS. The data were not available in 2. Elements of the preoperative and discharge neurological examination were assigned a score and compared by a paired t-test. There was a statistically insignificant improvement in the neurological score. A small but statistically significant decline in Karnofsky score was identified post-operatively in these recurrent tumor patients. Their hospital average length of stay increased with declining Karnofsky score. These prospective clinical observations confirmed our previous conclusion that brain tumor PDT was safe. The clinical studies are supported in part by grant CA 43892 awarded by DHHS/NIH/NCI.

Although many workers have used photodynamic therapy to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We report on the use of a targeted polycationic photosensitizer conjugate between poly-L-lysine and chlorin(e6) that can penetrate the Gram (-) outer membrane together with red laser light to kill Escherichia coli and Pseudomonas aeruginosa infecting excisional wounds in mice. We used genetically engineered luminescent bacteria that allowed the infection to be imaged in mouse wounds using a sensitive CCD camera. Wounds were infected with 5x10⁶ bacteria, followed by application of the conjugate in solution and illumination. There was a light-dose dependent loss of luminescence as measured by image analysis in the wound treated with conjugate and light, not seen in control wounds. This strain of E coli is non-invasive and the infection in untreated wounds spontaneously resolved in a few days and all wounds healed equally well showing the photodynamic treatment did not damage the host tissue. P aeruginosa is highly invasive and mice with untreated or control wounds all died while 90% of PDT treated mice survived. PDT may have a role to play in the rapid treatment of infected wounds in view of the worldwide rise in antibiotic resistance.

Photodynamic therapy (PDT) was performed with a new photosensitizer, a water soluble form of chlorins (Radachlorin, Russia) possessing an absorption peak around 662 nm. As light source there was used the diode laser (ML-662-SP, Russia) with 662 nm wavelength and 2.5 W optical power. The sensitizer had passed broad pre-clinical in vitro and in vivo studies, which showed safety and efficiency of it. PDT was applied to 51 patients with basal cell cancer of the skin (about 60% of all cases), breast cancer, lip cancer, melanoma, cancer of esophagus, stomach, and rectum, cancer and leucoplacia of vulva, malignant ganglioneuroma, sarcoma of soft tissue, cancer and reticular sarcoma of thyroid gland, cancer of ductus choledochus. Most of non-basalioma patients had either forth stage or recurrence of disease. The sensitizer was injected intravenously or applied externally (Radachlorin gel). There were used surface, endoscopic, and interstitial ways of irradiation. Full tumor regression with excellent cosmetic effect was reached in 100% cases of 1-3 stage basal cell cancer patients treated with intravenous Radachlorin injection. In most other (non-basalioma) cases significant regression of tumors and improvement of life quality of patients (recanalization and regain of conductivity) was obtained.

The light dosimetry for photodynamic therapy (PDT)for superficial lesions is concerned with ensuring sufficient light in the superficial tissue layer to achieve efficacious PDT. The light dosimetry for bulky tumors is concerned with the maximum depth of effective treatment while expecting over exposure of the tumor surface. The light delivered to a tissue surface does not equal the light received by the superficial region of that tissue. Backscattered light from the underlying tissues augments the surface irradiance to yield a higher fluence rate (W/cm²)in the target superficial tissue layer. The effective irradiance of treatment light, E [W/cm² ],seen by a superficial lesion is approximated: E =Eo(1 + 2R(1 +r_i)/(1 -r_i))=Eo(1 +6R)where Eo is the irradiance delivered to the surface, R is the fraction of incident light that escapes the tissue as observable reflectance (typically about 0.30-0.60),and r_i is the total internal reflection of light attempting to escape at the air/tissue surface (about 0.50).Hence the factor (1 +6R)varies from 2.8-4.6.The backscattered light significantly affects the treatment light dose for superficial lesions. The light within a bulky tumor is approximated: E =Eo k exp(-z/delta),where z is the depth in the tissue, k is a backscatter term, k =3 +5.1R -2exp(- 9.7R)(eg.,k =4.1-5.9 for R =0.30-0.60),and delta is the 1/e optical penetration depth (typically about 0.3-0.5 cm).

The transition of the tumor fluorescence from auto fluorescence towards PpIX fluorescence was studied under spectral and spatial resolution in an in-vivo tumour model. Human tumour cells were embedded on the chorioallantois membrane (CAM) of fertilised hen's eggs. A time period of 8 days is sufficient to grow tumours of a size of several millimeters. After the application of ALA and h-ALA the intensity and the wavelength spectra of the fluorescence were observed under blue light exposure (lambda) = 405 nm) by the spectrometer SpectraCube. 1-2 hours after the application of the photosensitizer the spectra show the yield of the typical double peak structure of PpIX.

Photodynamic therapy (PDT) is gradually gaining widespread acceptance as an alternative or adjunct therapy to standard oncologic treatment modalities. Effective PDT treatment is dependent on the interaction of the photosensitizer, treatment light, and molecular oxygen. Much room for improvement exists in the area of PDT dosimetry, especially for deep-seated tumors. To this end, multi-sensory fiber optic probes that detect the fluence rate have been developed. Selected fluorophores are placed in grooves at multiple (1-5) positions along a 250micrometers optical fiber. PLS-based deconvolution of the detected fluorescence emission spectrum yields the fluorescence intensity, and hence the fluence rate, at each sensor location. Single- fluorophore probes were used to elucidate properties of individual sensors. Results with these single-sensor probes, performance with PLS-based algorithm, and preliminary performance of multi-sensor probes will be presented.

The construction of a software platform for planning of photodynamic therapy (PDT) treatments is described. Its use is illustrated by the planning of a treatment of prostate cancer using multiple interstitial optical fiber sources. The effects of changing tissue optical properties, of photosensitizer photobleaching and of altering the power distribution between the sources are demonstrated. Validation tests of the PDT dose calculation algorithms and the software implementation of these are included. The possibility of compensating for misplaced sources is shown and confirmed experimentally in a tissue-simulating phantom. The future development of this platform and its integration into a complete solution planning-delivery-control platform is discussed.

Photodynamic therapy (PDT) treatments were performed on suspensions of AML5 cells incubated with ALA-induced PpIX with either 15 mW/cm², 45 mW/cm² or 90 mW/cm² pulsed 523 nm light. Singlet oxygen (¹O₂) luminescence measurements were carried out using a detection system including a near-infrared (NIR) sensitive photomultiplier tube (PMT). Cell viability was determined at several time points during treatments using the propidium iodide (PI) flow cytometry assay. Cumulative ¹O₂ measurements were compared to cell viability for all experiments. Preliminary results show that average cell viability increased with increasing treatment irradiance. Cell viability was found to correlate well with absolute cumulative ¹O₂ luminescence measurements during treatment.

An isotropic-detector-based system was compared with a flat-photodiode-based system in patients undergoing Pleural photodynamic therapy. Isotropic and flat detectors were placed side by side in the chest cavity, for simultaneous in vivo dosimetry at surface locations for twelve patients. The treatment used 630nm laser to a total light irradiance of 30 J/cm² (measured with the flat photodiodes) with photofrin IV as the photosensitizer. Since the flat detectors were calibrated at 532nm, wavelength correction factors (WCF) were used to convert the calibration to 630nm (WCF between 0.542 and 0.703). The mean ratio between isotropic and flat detectors for all sites was linear to the accumulated fluence and was 3.4+/- 0.6 or 2.1+/- 0.4, with or without the wavelength correction for the flat detectors, respectively. The micrometers _eff of the tissues was estimated to vary between 0.5 to 4.3 cm^-1 for four sites (Apex, Posterior Sulcus, Anterior Chest Wall, and Posterior Mediastinum) assuming microsecond(s) ' = 7 cm^-1. Insufficient information was available to estimate micrometers _eff directly for three other sites (Anterior Sulcus, Posterior Chest Wall, and Pericardium) primarily due to limited sample size, although one may assume the optical penetration in all sites to vary in the same range (0.5 to 4.3 cm^-1).

The efficiency of photodynamic therapy (PDT) using 5- aminolevulinic acid (5-ALA) is essentially determined by an optimal choice of sensitization means, among which the application method is one of the most perspective due to high permeability of a skin for 5-ALA. The aim of present work is optimization of sensitization process with ALA. We have used the possibility of 5-ALA transparency in applicator (outside of tissue) while protoporphyrin-IX, formed in sensitized tissue, has sufficient absorption for providing PDT. We have developed 5-ALA containing applicator on the basis of transparent biodegradable polymers, which serve as a programmed source of 5-ALA in the zone of their contact with pathological tissue. The investigations carried out on mice with the solid form of leucosis p-388, have shown that developed applicator provides effective sensitization of pathological tissue, supporting high concentration of photosensitizer in tissue during the whole time of application (up to week). The experiments in vivo have demonstrated high efficiency of PDT. The preliminary clinical researches allow to draw a conclusion about its perspectivity for photodynamic treatment of skin malignancies.

In response to photodynamic therapy (PDT), many cells in culture or within experimental tumors are eliminated by apoptosis. PDT with photosensitizers that localize in or target mitochondria, such as the phthalocyanine Pc 4, causes prompt release of cytochrome c into the cytoplasm and activation of caspases-9 and -3, among other caspases, that are responsible for initiating cell degradation. Some cells appear resistant to apoptosis after PDT; however, if they have sustained sufficient damage, they will die by a necrotic process or through a different apoptotic pathway. In the case of PDT, the distinction between apoptosis and necrosis may be less important than the mechanism that triggers both processes, since critical lethal damage appears to occur during treatment and does not require the major steps in apoptosis to be expressed. We earlier showed, for example, that human breast cancer MCF-7 cells that lack caspase-3 are resistant to the induction of apoptosis by PDT, but are just as sensitive to the loss of clonogenicity as MCF-7 cells stably expressing transfected procaspase-3. Many photosensitizers that target mitochondria specifically attack the anti-apoptotic protein Bcl-2, generating a variety of crosslinked and cleaved photoproducts. Recent evidence suggests that the closely related protein Bcl-xL is also a target of Pc 4-PDT. Transient transfection of an expression vector encoding deletion mutants of Bcl-2 have identified the critical sensitive site in the protein that is required for photodamage. This region contains two alpha helices that form a secondary membrane anchorage site and are thought to be responsible for pore formation by Bcl-2. As specific protein targets are identified, we are becoming better able to model the critical events in PDT-induced cell death.

We previously classified photosensitizing agents based on sites of photodamage: mitochondria, lysosomes and the plasma membrane. More recent studies have indicated that the first target for the mitochondrial sensitizers is the anti-apoptotic protein bcl-2. Loss of bcl-2 results in a high bax/bcl-2 ratio, leading to an apoptotic response involving cytochrome c translocation. PDT with sensitizers that target lysosomes causes the release of lysosomal proteases that catalyze cleavage of the protein bid to a truncated form that can also initiate an apoptotic response. When the PDT target includes the plasma membrane, we found a greatly impaired apoptotic response, associated with caspase-3 photodamage. Sensitizers that localize in only lysosomes also catalyze variable levels of caspase photodamage, but apoptosis is only slightly impaired. PDT appears to be a highly-selective means for eradication of bcl-2, lysosomes or caspases, and can be a potentially useful tool in apoptosis research.

Photodynamic therapy (PDT) can induce a variety of tissue changes, including apoptosis, oncosis, and vascular responses. A preliminary study using two non-invasive imaging techniques, ultrasound backscatter microscopy/spectroscopy (UBM/UBS) and optical coherence/Doppler tomography (OCT/ODT), is presented. Photofrin PDT of melanoma was studied using a mouse model and imaged by both modalities in vivo. Post PDT, increase in the signal intensity and change in the backscatter spectrum were observed in UBM/UBS. A transient increase in the signal attenuation was observed by OCT and changes in the neovasculular blood flow were detected using ODT. Additional in vitro experiments were performed to examine the possible causes of the observed signal changes.

PDT included necrosis in brain tissue and an intracranial tumor has been quantified for various photosensitizers, and it has been shown to be dependent on the sub-cellular localization of these photosensitizers. In quantifying non- necrotic biological endpoints, such as PDT induced apoptosis, the expression and translation of apoptosis inhibiting or promoting genes is of considerable importance. We studied the susceptibility of two glioblastoma cell lines to under go apoptotic cell death following photodynamic treatment with either Photofrin or delta-aminolevulinic acid (delta) ALA) in vivo. Murine 9L Gliosarcoma cells or human U87 Glioblastoma cells were implanted into the cortex of rats, and following 12 or 14 days of growth respectively, subjected to either Photofrin-mediated PDT or ALA-mediated PDT. 9L gliosarcoma cells express the phosphatase Tensin homologue (PTEN) tumor suppressor gene while in U87 cells PTEN is mutated. Differences in the Photofrin mediated PDT induced apoptosis were noted between the two different cell lines in vivo, suggesting that Photofrin mediated PDT may be dependent on apoptotic pathways. ALA induced PPIX showed higher selectivity towards 9L than Photofrin mediated PDT. These studies suggests that PDT could be used as an effective treatment for intracranial neoplasm. Endogenous photosensitizers such as ALA could be used to promote apoptosis in tumor cells due to PDT treatment and thereby minimize the extent of necrotic infarction in the surrounding normal brain.

Classical photodynamic therapy (PDT) has a drawback of limited penetration of visible light. It has been proposed that by utilizing two-photon absorption (TPA), where illumination is carried out at near-IR wavelengths falling into tissue transparency window, the PDT can be used for deeper treatment of tumors. Here we introduce new porphyrin photosensitizer 5-(4-diphenylaminostilbene),15-(2,6-dichlorophenyl)-21H,23H- porphine (hereafter referred as DPASP) with greatly enhanced TPA cross-section in near-IR range of wavelengths. The design of DPASP was based on structure-property relationships, empirically known to enhance TPA cross-section in organic (pi) -conjugated chromophores. In our case introduction of a 4-(diphenylaminostilbene)-substituent into the 5-position of the tetrapyrrole ring results in 20-fold enhancement of TPA cross-section at (lambda) _exc = 780 nm as compared with parent molecule 5-phenyl,15-(2,6-dichlorophenyl)-21H,23H-porphine (DPP). The high value of TPA cross-section of DPASP enables to reliably detect for the first time an efficient luminescence of singlet oxygen produced upon two-photon excitation of porphyrin. Singlet oxygen luminescence was also measured upon two-photon excitation of several other porphyrins including water-soluble derivative 5,10,15,20-tetrakis-(4-N-methylpyridyl)-21H,23H-porphine (TmpyP).

Although 5-aminolevulinic acid (ALA) has several advantages over other photosensitizers, its hydrophilic nature gives rise to relatively poor transport across cell membranes. Esterification of ALA is a commonly used strategy to improve the effectiveness of ALA. In this study, the effectiveness of photodynamic therapy (PDT) in human glioma spheroids incubated in ALA, or ALA esters, is investigated. Spheroid survival and growth are monitored following PDT at representative drug concentrations and light fluences. It is shown that the response of human glioma spheroids to PDT with lipophilic ester derivatives, such as benzyl-ALA and hexyl-ALA, is equivalent to that observed with ALA, however, this equivalency is observed for ester concentrations 10 to 20 times lower than the parent compound.

The effectiveness of low-fluence rate PDT on human glioma spheroids incubated in 5-aminolevulinic acid (ALA) or hexyl- ALA, is investigated. Spheroid survival is monitored following PDT at representative drug concentrations, light fluences and fluence rates. It is shown that, for above threshold fluences, significant PDT response can be obtained at a fluence rate of 5 mW cm^-2. At this fluence rate, the response of human glioma spheroids to PDT with lipophilic ester derivatives, such as hexyl-ALA, is equivalent to that obtained with ALA, however, this equivalency is observed for ester concentrations 20 times lower than the parent compound. The efficacy of PDT is significantly reduced at a sub-threshold fluence of 25 J cm^-2. Spheroid response appears to be somewhat fluence rate dependent at sub-threshold fluences - survival is marginally poorer at the higher fluence rate (25 mW cm^-2) investigated. In addition, the efficacy of PDT at 25 J cm^-2 depends significantly on photosensitizer concentration at the lowest fluence rate investigated (5 mW cm^-2).

A new tumor detection method by use of sonodynamic chemiluminescence was proposed in our previous work. In this paper, we further improved the diagnosis sensitivity by use of Gallium-porphyrin analogue ATX-70, one of the most active sonosensitizer found. In vitro experiments, sono-chemiluminescence of ATX-70 + FCLA system is about two times stronger than that of HpD + FCLA system. The sono-chemiluminescence was inhibited by ¹O₂ scavenger, but was not affected by other free radical scavenger. The mechanism of sonosensitizing was discussed. In vivo experiments, a more clearly tumor diagnostic image was obtained.

Background: Subjective measures are considered the gold standard in palliative care evaluation, but no studies have evaluated palliative photodynamic therapy (PDT) subjectively. If PDT is to be accepted as a palliative therapy for later-stage obstructing esophageal and lung cancer, evidence of its effectiveness and acceptability to patients must be made known. Study Design/Materials and Methods: This ongoing study's major aim is to evaluate subjective outcomes of PDT in patients with obstructing esophageal and lung cancer. Existing measures of health status, dysphagia and performance status were supplemented with an instrument developed to evaluate PDT symptom relief and side effect burden, the PDT Side Effects Survey (PSES). Results: PDT patients treated with porfimer sodium (Photofrin) and 630-nm light experienced reduced dysphagia grade and stable performance status for at least one month after PDT (N= 10-17), but these effects did not necessarily persist at three months. Fatigue, appetite and quality of life may be the most burdensome issues for these patients. Conclusions: Preliminary data suggest that the PSES is an acceptable and valid tool for measuring subjective outcomes of palliative PDT. This study is the first attempt to systematically evaluate subjective outcomes of palliative PDT. Multi-center outcomes research is needed to draw generalizable conclusions that will establish PDT's effectiveness in actual clinical practice and enhance the wider adoption of PDT as a cancer symptom relief modality.

Photodynamic Therapy (PDT) is becoming a popular treatment modality for many superficial cancers and several non-malignant diseases. The use of PDT to treat solid tumors has been limited because there is currently is no clinically acceptable method of either characterizing the optical parameters of a target tissue or of determining dose delivered to the target tissue volume as delivered by a fibreoptic terminated in a cylindrical diffusing tip. Accurate light dosimetry methods, such as the Monte Carlo method, are of limited clinical utility. In this paper we describe the use of the P3-Approximation to optically characterize a light scattering and absorbing medium. Tissue characterization calculations made using the P3-Approximation are analytical and may be performed much faster than with numerical modeling. The process time needed to estimate the dose distribution is sufficiently short to permit iterative adjustment of the light source distribution to account for tissue inhomogeneities, in real time. P3-Approximation based optical dosimetry should be sufficiently fast to be incorporated into an iterative feedback control algorithm for the distribution of light across an interstitial source array. With the optical coefficients furnished by the P3-Approximation, the light dose delivered to the medium from a cylindrical fibreoptic source can be accurately calculated using a novel formulation of Diffusion Theory. The cylindrical fibreoptic diffuser is modeled as a Huygen's array: a finite yet continuous array of isotropic point sources. The predicted light fluence distribution from the Huygen's array compares favorably with experimental fluence measurements.