Interstitial Photodynamic Therapy Research Articles

Adenoid cystic carcinoma of the tongue base treated with ultrasound-guided interstitial photodynamic therapy: A case study

Adenoid cystic carcinoma is a malignant neoplasm arising from the salivary glands. It accounts for 10-15% of all salivary gland neoplasms, representing 1-2% of malignant neoplasms of the head and neck. It is characterized by slow growth, diffuse invasion and potential to produce distant metastases, mainly to the lungs and bone. We present a case of adenoid cystic carcinoma of the base of tongue treated with ultrasound guided transcutaneous interstitial photodynamic therapy (PDT) as a salvage treatment.

PL11 Interstitial photodynamic therapy (IPDT)

Acupuncture is widely used in clinical practice. According to traditional acupuncture theory, the Neiguan acupoint (PC6) is one of the most commonly used acupoints and is indicated for treating cardiovascular-related disorders. We present the case of a 27-year-old female who had been diagnosed with ventricular septal defect and had undergone surgery to repair the defect at the age of 11 years. The patient had no obvious symptoms, such as palpitations and difficulty breathing. However, while performing electrocardiography (ECG), we found that she suffered from arrhythmia, and therefore, we treated her by acupuncture at the left PC6. An ECG monitor was used to record data during the entire acupuncture procedure, which was divided into the following three segments: prior to, during, and after acupuncture. Various indices of heart rate variability (HRV) were then determined and analyzed. The results indicate that acupuncture can regulate the HRV effectively; however, more studies are needed to confirm this finding.

Interstitial Photodynamic Therapy of Brain Tumors

Malignant gliomas are associated with poor prognosis. Photodynamic therapy (PDT), relying on light-activated toxicity of a photosensitizer, has been investigated as a means for improving patient survival. This review presents a summary of clinical results obtained with PDT using different photosensitizers for treating brain malignancies. Particular emphasis is on the use of 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX). PpIX is a potent photosensitizer that displays good tumor-selective uptake and characteristic fluorescence. Here, we present clinical data on PpIX biodistribution and PpIX photobleaching kinetics, indicating high tumor selectivity and rapid photobleaching. These data provide the motivation for the use of a dosimetry model aiming at a complete consumption of PpIX during PDT. This dosimetry model, referred to as the advanced photobleaching model, has been implemented for interstitial PDT (iPDT) relying on stereotactic positioning of radial light diffusers within the tumor volume. A summary of preliminary results from our clinical trial on ALA-mediated brain-iPDT is presented. Finally, recent developments of brain-PDT are discussed with respect to their potential to improve treatment efficacy. We have identified individualized dosimetry, the use of multiple photosensitizers and the combination of photosensitizer and immune response modifiers as the most promising strategies for further preclinical and clinical research.

Cystic hygroma treated with ultrasound guided interstitial photodynamic therapy: Case study

A cystic hygroma, or hygroma cysticum coli, was first described by Wernher in 1843 as a benign harmatoma of the lymphatic system [1]. They are most commonly known to affect the posterior triangle of the neck (70—80% of cases); however, the axilla, superior mediastinum and chest wall have also occasionally been involved. Although of unknown aetiology, theories suggest that they could originate from the growth arrest of primitive lymph channels. This causes the impediment of peripheral lymphatic’s resulting in the formation of fluid-filled sacs. The condition usually presents at birth or early infancy with variable size. It can be either unilocular or multilocular which in both cases transilluminate during examination. Symptoms can be severe when involving the neck giving rise to progressive airway obstruction and dysphagia and/or odynophagia. Surgical debridement or excision of small lesions has been recommended. However, large size lesions are difficult to excise due to increase risk of morbidity and disfigurement.

Lipophilic photosensitizer administration via the prostate arteries for photodynamic therapy of the canine prostate

Current limitations of interstitial photodynamic therapy (PDT) for treatment of prostate cancer include low drug selectivity after intravenous (i.v.) administration and incomplete ablation of glandular tissue. To overcome these limitations, intra-arterial (i.a.) injection of a photosensitizer was tested in a canine model. A lipophilic photosensitizer, SL052 formulated in liposomes or dissolved in dimethyl sulphoxide (DMSO), was injected into male dogs as an intravenous injection or intra-arterially via the prostate arteries. Optical fibers were inserted into the prostate 3h after i.v. or immediately following i.a. drug delivery. Laser light was delivered through the fibers in cycles controlled by a computer-driven switch. Drug concentration (fluorescence) and light transmission in prostate tissue were monitored during the course of PDT. Side effect profile and completeness of prostate gland ablation were the primary parameters compared among treatment groups. Control animals received drug-only or light-only treatment. Thirteen dogs were treated by PDT mediated by i.a. injection of SL052 dissolved in DMSO and attained either complete ablation of prostatic glandular tissue or significant reduction of prostate volume compared with that of pre-PDT (p<0.0001). When compared to i.v. administration the i.a. route resulted in more complete photo-ablation. Associated side effect included acute urinary retention which resolved overtime. No incontinence was observed. With careful tailoring of PDT drug and light doses, interstitial PDT with i.a. injection of SL052-DMSO has the potential to provide effective treatment for prostate disease.

Lacrimal gland mantle lymphoma treated with photodynamic therapy: Overview and report of a case

We present the successful use of interstitial photodynamic therapy in the treatment of lacrimal gland mantle cell lymphoma associated with cervical and axillary lymphadenopathy in a 59-year-old female.

A heterogeneous optimization algorithm for reacted singlet oxygen for interstitial PDT.

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.

System for interstitial photodynamic therapy with online dosimetry: first clinical experiences of prostate cancer

The first results from a clinical study for Temoporfin-mediated photodynamic therapy (PDT) of low-grade (T1c) primary prostate cancer using online dosimetry are presented. Dosimetric feedback in real time was applied, for the first time to our knowledge, in interstitial photodynamic therapy. The dosimetry software IDOSE provided dose plans, including optical fiber positions and light doses based on 3-D tissue models generated from ultrasound images. Tissue optical property measurements were obtained using the same fibers used for light delivery. Measurements were taken before, during, and after the treatment session. On the basis of these real-time measured optical properties, the light-dose plan was recalculated. The aim of the treatment was to ablate the entire prostate while minimizing exposure to surrounding organs. The results indicate that online dosimetry based on real-time tissue optical property measurements enabled the light dose to be adapted and optimized. However, histopathological analysis of tissue biopsies taken six months post-PDT treatment showed there were still residual viable cancer cells present in the prostate tissue sections. The authors propose that the incomplete treatment of the prostate tissue could be due to a too low light threshold dose, which was set to 5 J∕cm2.

Imaging Tumor Variation in Response to Photodynamic Therapy in Pancreatic Cancer Xenograft Models

A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.

Evaluation of Antitumor Efficiency of Experimental Interstitial Photodynamic Therapy on the Model of M1 Sarcoma

Antitumor efficiency of interstitial photodynamic therapy was evaluated in experiments on outbred albino rats with implanted M-1 sarcoma. Interstitial photodynamic therapy was carried out using one diffusor at different output power and duration of exposure. The percentage of complete regression of the tumors increased with increasing exposure parameters.

Ultrasound‐guided photodynamic therapy for deep seated pathologies: prospective study

Interstitial photodynamic therapy remains an attractive remedial option in minimally invasive surgery. Our aim in this prospective study was to evaluate the outcome following ultrasound-guided iPDT of deep-seated pathologies. Patients' reports on quality of life with clinical and radiological evaluation were the main end point parameters used to assess the outcome. Sixty-eight patients were referred to the UCLH Head and Neck Centre for treatment of various deep-seated pathologies involving the head and neck region, upper and lower limbs. All patients underwent interstitial photodynamic therapy under general anaesthesia, using 0.15 mg/kg mTHPC as the photosensitising agent. Following treatment, patients were followed-up for a mean of 7 months. All three patients who presented with visual problems reported improvement after treatment. Also, 14/17 patients reported improvement of breathing. Improvement of swallowing was reported by 25/30 patients; while speaking improvement was evident in 16/22 patients and 33/40 reported reduction in the disfigurement caused by their pathology. All five patients with impeded limb function reported some degree of improvement. Clinical assessment showed that half of the patients had 'good response' to the treatment and a third reported 'moderate response' with two patients being free of disease. Radiological assessment comparing imaging 6-week post-PDT to the baseline showed stable pathology with no change in size in 13 patients, minimal response in 18 patients, moderate response in 23 patients and significant response in 11 patients. This study on 68 patients with deep-seated pathologies undergoing interstitial photodynamic therapy provided evidence that PDT can be the fourth modality in the management of tissue disease.

Ultrasound guided interstitial photodynamic therapy of deep seated lesions

Introduction: Photodynamic therapy is a minimally invasive therapy that results from the interaction between a photosensitiser, oxygen and light. The delivery of light can by either by surface illumination or interstitial application.

Chondrosarcoma of the hyoid treated with interstitial photodynamic therapy: Case study

Chondrosarcoma;Hyoid;PhotodynamictherapyChondrosarcoma is a malignancy that is cartilaginous in ori-gin and represents approximately 25% of all primary osseousneoplasms. Chondrosarcomas are rare with 90 new cases ayearreportedintheUK.Ofthese,only10%occurintheheadandneck.Peakincidenceisbetweentheagesof30—50,withno apparent correlation with gender [1,2].There are two common grading systems for chondrosar-comas. They can be graded 1—3, with 1 being the leastaggressive and 3 the most. Alternatively, chondrosarcomasare graded low or high grade, with low grade tumours char-acterised by well-differentiated cells and high grade poorlydifferentiated, with a high mitotic rate [1,2].Approximately 90% of conventional chondrosarcomas arelow to intermediate grade that have low metastatic poten-tial, and the rest are high grade or grade 3 lesions with ahigh metastatic rate. The 5-year survival rate of patientswith grade 1, 2, and 3 tumors were 90%, 81%, and 43%,

1277: Sonographically Guided Percutaneous Interventional Therapies for 5-8 cm Noninfiltrating Hepatocellular Carcinoma: Long-term Therapeutic Efficacy Analysis

This study was To investigate the therapeutic efficacy on patients with 5-8 cm noninfiltrating hepatocellular carcinoma (HCC) treated with percutaneous ethanol injection (PEI), percutaneous acetic acid injection(PAI), percutaneous hot saline injection (PHSI), interstitial photodynamic therapy (IPDT),radiofrequency ablation (RFA), and combined interventional therapies (transcatheter arterial embolization plus PEI or RFA).

Chondrosarcoma of the hyoid treated with interstitial photodynamic therapy

Interstitial PDT was performed using a baseline MRI scan as a guide. Clinical and radiological assessments at follow-up showed a promising reduction in lesional size. Conclusion Conventional management of chondrosarcoma includes conservative, intra-lesional steroids, chemotherapeutic drugs, radiotherapy and surgical excision. Unfortunately none of which are curative as the lesion inevitably recurs. The authors commend PDT as a repeatable treatment option in management of these lesions. from 1st Scientific Meeting of the Head and Neck Optical Diagnostics Society London, UK. 14 March 2009

Ultrasound guided interstitial photodynamic therapy of deep seated lesions

Ultrasound guided interstitial photodynamic therapy of deep seated lesions

The design of a robotic multichannel platform for photodynamic therapy.

A compact robotic platform is designed for simultaneous multichannel motion control for light delivery and dosimetry during interstitial photodynamic therapy (PDT). Movements of light sources and isotropic detectors are controlled by individual motors along different catheters for interstitial PDT. The robotic multichannel platform adds feedback control of positioning for up to 16 channels compared to the existing dual-motor system, which did not have positioning encoders. A 16-channel servo motion controller and micro DC motors, each with high resolution optical encoder, are adopted to control the motions of up to 16 channels independently. Each channel has a resolution of 0.1mm and a speed of 5cm/s. The robotic platform can perform light delivery and dosimetry independently, allowing arbitrary positioning of light sources and detectors in each catheter. Up to 16 compact translational channels can be combined according to different operational scheme with real-time optimal motion planning. The characteristic of high speed and coordinating motion will make it possible to use short linear sources (e.g., 1- cm) to deliver uniform PDT treatment to a bulk tumor within reasonable time by source stepping optimization of multiple sources simultaneously. Advanced robotic control algorithm handles the various unexpected circumstance in clinical procedure, e.g., positiontorque/current control will be applied to prevent excessive force in the case of resistance in the fiber or motorized mechanism. The robotic platform is fully compatible with operation room (OR) environment and improves the light delivery and dosimetry in PDT. It can be adopted for diffusing optical tomography (DOT), spectroscopic DOT and fluorescent spectroscopy.

SU‐FF‐T‐451: Determination of Optical Properties in a Heterogeneous Turbid Media Using a Cylindrical Diffusing Fiber

Purpose: For interstitial photodynamic therapy (PDT), cylindrical diffusing fibers (CDF) are often used to deliver light. This study examines the feasibility and accuracy of using the CDF to characterize the absorption (μa) and reduced scattering (μs′) coefficients of heterogeneous turbid media. Method and Materials: Measurements were done in prostate simulating phantoms. Liquid and solid phantoms were used (homogeneous and inhomogeneous, with optical properties of ⌈s′=7.5cm−1 and ⌈a=0.1cm−1). The inhomogeneous phantom had three tumor simulating inhomogeneities (⌈s′=15cm−1 and ⌈a=0.1, 0.3 and 0.9 cm−1). Linear light sources of varying lengths were placed inside the phantom through the atheter. In‐air measurements were performed to characterize the intensity profile of each linear fiber. Fluence rate was measured using a 0.5mm scattering tip isotropic detector that was moved along each catheter using a motorized probe. To ensure that the optimization technique was accurate, we measured the optical properties of each phantom using a well established method. Results: Optical properties were measured in a homogeneous liquid phantom by measuring the fluence rate along a 2mm pint source and compared against results using linear source method. The absorption coefficients were then determined using a method in which ⌈s′ was kept fixed. Using the determination of ⌈s′ from the homogeneous fit, we were able to determine the absorption coefficients with a standard (maximum)deviation of 5.6 % (9.8%) while using the fixed ⌈'s′ method, the standard (maximum) deviation were 6.9% (19%). Conclusion: We showed that it is possible to accurately determine the optical properties inhomogeneities (⌈a) using linear sources to a relative accuracy of better than 10%. Sensitivities for determination of ⌈s′ is quite poor using linear sources. Linear source method is more sensitive to detector optical heterogeneities. The effect of intensity profile on determination of the absorption coefficient ⌈a is relatively small — this is important for forward calculation.

Management of deep-seated malformations with photodynamic therapy: a new guiding imaging modality

Photodynamic therapy is an emerging technology and results from the interactions between a photosensitiser, oxygen and light. The delivery of light may either be by surface illumination or by interstitial application. We describe the first clinical application of ultrasound-guided interstitial photodynamic therapy (US-iPDT). A total of 23 treatments with meta-tetra-hydroxyphenyl chlorine (mTHPC) and ultrasound-guided interstitial photodynamic therapy were performed on 21 patients with various conditions at the Head & Neck Centre, University College London Hospital. The needles could be clearly identified during insertion in all 23 treatments, and it was possible to guide parallel needle insertions using ultrasound. Although the resolution of ultrasound is not as high as that of other imaging modalities [i.e. computed tomography (CT) and magnetic resonance imaging (MRI)] it was satisfactory in identifying the centre and the peripheries of the pathological lesions. Ultrasound is very easy to perform, non-invasive, relatively inexpensive, quick, convenient, non-ionising, suited to the imaging of soft tissues and does not cause any discomfort. Ultrasound can be used to guide 'real-time' photodynamic therapy in deep-seated tumours and other malformations and can augment the information from other imaging modalities without affecting the patient's treatment outcome.

Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer

With the development of new photosensitizers that are activated by light at longer wavelengths, interstitial photodynamic therapy (PDT) is emerging as a feasible alternative for the treatment of larger volumes of tissue. Described here is the application of PDT treatment planning software developed by our group to ensure complete coverage of larger, geometrically complex target volumes such as the prostate. In a phase II clinical trial of TOOKAD vascular targeted photodynamic therapy (VTP) for prostate cancer in patients who failed prior radiotherapy, the software was used to generate patient-specific treatment prescriptions for the number of treatment fibres, their lengths, their positions and the energy each delivered. The core of the software is a finite element solution to the light diffusion equation. Validation against in vivo light measurements indicated that the software could predict the location of an iso-fluence contour to within approximately ±2 mm. The same software was used to reconstruct the treatments that were actually delivered, thereby providing an analysis of the threshold light dose required for TOOKAD-VTP of the post-irradiated prostate. The threshold light dose for VTP-induced prostate damage, as measured one week post-treatment using contrast-enhanced MRI, was found to be highly heterogeneous, both within and between patients. The minimum light dose received by 90% of the prostate, D90, was determined from each patient's dose–volume histogram and compared to six-month sextant biopsy results. No patient with a D90 less than 23 J cm−2 had complete biopsy response, while 8/13 (62%) of patients with a D90 greater than 23 J cm−2 had negative biopsies at six months. The doses received by the urethra and the rectal wall were also investigated.