Stuart K. Bisland

University of California, San Francisco, San Francisco, CA, United States

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Publications (48)84.14 Total impact

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    ABSTRACT: This study investigates the effects of photodynamic therapy (PDT) on the structural integrity of vertebral bone in healthy rats. To determine the short-term (1 week) and intermediate term (6 weeks) effects of a single PDT treatment on the mechanical and structural properties of vertebral bone. Spinal metastasis develops in up to one-third of all cancer patients, compromising the mechanical integrity of the spine and thereby increasing the risk of pathologic fractures and spinal cord damage. PDT has recently been adapted to ablate metastatic tumors in the spine in preclinical animal models. However, little is known about the effects of PDT on the structural integrity of vertebral bone. A single PDT treatment was administered to healthy Wistar rats at photosensitizer and light doses known to be effective in athymic rats bearing human breast cancer metastases. At both 1 and 6 weeks posttreatment, changes in trabecular architecture, global stiffness and strength of vertebrae were quantified using micro-CT stereological analysis and axial compression testing. At 6 weeks, there was a significant increase in bone volume fraction (to 55.7 +/- 11.1% vs. 38.5 +/- 6.4%, P < 0.001) and decrease in bone surface area-to-volume ratio (16.9 +/- 5.0/mm vs. 22.8 +/- 4.5/mm, P = 0.001), attributed to trabecular thickening (130 +/- 40 microm vs. 90 +/- 20 microm, P < 0.001). Similar trends were found at 1 week after PDT. There was a significant increase in stiffness from control (306 +/- 123 N/mm) at 1 week (399 +/- 150 N/mm, P = 0.04) and 6 weeks (410 +/- 113 N/mm, P = 0.05) post PDT. There was a positive trend toward increased ultimate stress at 1 week, which became statistically significant at 6 weeks compared with control (39.3 +/- 11.3 MPa vs. 27.5 +/- 9.5 MPa control, P = 0.002). Not only may PDT be successful in ablating metastatic tumor tissue in the spine, but the positive effects of PDT on bone found in this study suggest that PDT may also improve vertebral mechanical stability.
    Spine 02/2010; 35(3):272-7. · 2.16 Impact Factor
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    ABSTRACT: Photodynamic therapy uses nonthermal coherent light delivered via fiber optic cable to locally activate a photosensitive chemotherapeutic agent that ablates tumor tissue. Owing to the limitations of light penetration, it is unknown whether photodynamic therapy can treat large osseous tumors. We determined whether photodynamic therapy can induce necrosis in large osseous tumors, and if so, to quantify the volume of treated tissue. In a pilot study we treated seven dogs with spontaneous osteosarcomas of the distal radius. Tumors were imaged with MRI before and 48 hours after treatment, and the volumes of hypointense regions were compared. The treated limbs were amputated immediately after imaging at 48 hours and sectioned corresponding to the MR axial images. We identified tumor necrosis histologically; the regions of necrosis corresponded anatomically to hypointense tissue on MRI. The mean volume of necrotic tissue seen on MRI after photodynamic therapy was 21,305 mm(3) compared with a pretreatment volume of 6108 mm(3). These pilot data suggest photodynamic therapy penetrates relatively large canine osseous tumors and may be a useful adjunct for treatment of bone tumors.
    Clinical Orthopaedics and Related Research 02/2009; 467(4):1028-34. · 2.79 Impact Factor
  • Stuart K. Bisland
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    ABSTRACT: Photodynamic therapy uses hirger doses of light and numerous photo-sensitizers to activate the killing of the sensitized tissue via singlet oxygen. The predominant target of PDT has been cancer, but it may also have application to other diseases. The combination of PDT with laser (light) therapy is very appropriate and valuable. Keywords:Photodynamic therapy(PDT)–singlet oxygen–mitochondria–ALA–PBR.
    12/2007: pages 81-88;
  • Stuart K. Bisland
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    ABSTRACT: There have been numerous reports describing the phenomena of low-level light therapy (LLLT) within the clinic and its broad application to alleviate pain, enhance the rate of wound healing, including spinal cord injury, reduce inflammation, improve learning, bolster immunity and combat disease. Yet, despite the breadth of potential applications for which bio-stimulation may prove beneficial, there persists a dramatic ignorance in our understanding of the signal pathways that govern these effects. At the cellular level, there exist a variety of endogenous chromophores such as cytochrome c oxidase, NADPH, FAD, FMN and other factors intrinsic to the electron transport chain in mitochondria that absorb light of specific wavelength and will undoubtedly have their role in bio-stimulation, however the dose dependency of effect with regard to total light fluence and fluence rate, as well as the importance of specific subcellular targeting, remains elusive. Furthermore, the translation of cellular response(s) in vitro to in vivo needs to be expounded. Clearly, a rigorous examination of bio-stimulatory parameters as a function of cellular and tissue response is necessary if we are to attain optimized, reproducible protocolsbasedonatrue scientific rationale for using bio-stimulation as a therapeutic modality in clinic. This paper introduces a number of the challenges we now face for advancing the bio-stimulation phenomena into the scientific mainstream by highlighting our current knowledge in this field as well as some of the research that we are conducting using LLLT in combination with photodynamic therapy. KeywordsLow-level light therapy–photobiomodulation–cytochrome c oxidase–apoptosis–mitochondria–laser–LED
    12/2007: pages 67-80;
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    ABSTRACT: This study investigates whether low-level light treatment (LLLT) can enhance the expression of peripheral-type mitochondrial benzodiazepine receptors (PBRs) on glioma-derived tumor cells, and by doing so promote the synthesis of protoporphyrin IX (PpIX) and increase the photodynamic therapy (PDT)-induced cell kill using 5-aminolevulinic acid (ALA). The endogenous photosensitizer, PpIX and related metabolites including coproporphyrin III are known to traffic into or out of the mitochondria via the PBRs situated on the outer mitochondrial membrane. Cells of astrocytic derivation within the brain express PBRs, while neurons express the central-type of benzodiazepine receptor. Astrocytoma-derived CNS-1 cells were exposed to a range of differing low-level light protocols immediately prior to PDT. LLLT involved using broad-spectrum red light of 600-800 nm or monochromatic laser light specific to 635 or 905 nm wavelength. Cells (5 x 10(5)) were exposed to a range of LLLT doses (0, 1, or 5 J/cm(2)) using a fixed intensity of 10 mW/cm(2) and subsequently harvested for cell viability, immunofluorescence, or Western blot analysis of PBR expression. The amount of PpIX within the cells was determined using chemical extraction techniques. Results confirm the induction of PBR following LLLT is dependent on the dose and wavelength of light used. Broad-spectrum red light provided the greatest cell kill following PDT, although LLLT with 635 nm or 905 nm also increased cell kill as compared to PDT alone. All LLLT regimens increased PBR expression compared to controls with corresponding increases in PpIX production. These data suggest that by selectively increasing PBR expression in tumor cells, LLLT facilitates enhanced tumor cell kill using ALA-PDT. This may further improve the selectivity and efficacy of PDT treatment of brain tumors.
    Lasers in Surgery and Medicine 10/2007; 39(8):678-84. · 2.46 Impact Factor
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    ABSTRACT: Vascularization of developing growth plates is integral to the process of endochondral ossification. We hypothesized photodynamic therapy could be used to initiate premature vascularization and calcification of growth plates in mice on the induction of vascular endothelial growth factor. Three-week-old transgenic mice that emit bioluminescence on activation of the vascular endothelial growth factor gene were treated with different regimens of benzoporphyrin derivative mono-acid-mediated photodynamic therapy in the right, proximal tibial growth plate. We quantified changes in vascular endothelial growth factor-related bioluminescence at times after photodynamic therapy in vivo. The expression of vascular endothelial growth factor protein and CD31-labeled vasculature in growth plates also were examined with growth plate histology. Measurements of limb length were assessed in vivo using conventional radiography and confirmed on harvesting. Mice exposed to repeat treatments of 10 J x2 displayed enhanced bioluminescence 2 weeks after photodynamic therapy. Histology confirmed increased vasculature immediately adjacent to the growth plates with evidence of physeal closure. At 4 weeks posttreatment, limbs were shortened by an average of 9.5% +/- 4.4% without complication, confirming the potential application of photodynamic therapy for physiodesis.
    Clinical Orthopaedics and Related Research 09/2007; 461:153-61. · 2.79 Impact Factor
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    ABSTRACT: ABSTRACTTOOKAD (WST09) is a new, long-wavelength palladium bacteriopheophorbide photosensitizer that targets tissue vasculature. The cutaneous phototoxicity of TOOKAD was assessed in normal rat and pig animal models and in patients in a Phase-I trial of TOOKAD-mediated photodynamic therapy (PDT) for recurrent prostate cancer. Controlled skin exposures were administered using solar-simulated light at various times after drug administration. Two different spectral ranges were used. In the first, the UV portion of the spectrum was removed (UV−) because UV irradiation in nondrugged control animals produced an erythema response at incident energy densities (J/cm2) lower than those required to induce a PDT response. In the second, the full solar spectrum (UV+) was used, and the potentiation by the photosensitizer of the UV-mediated minimum erythema dose was assessed. Results showed that the PDT skin response was negligible at clinical drug doses of 2 mg/kg for any period after administration at light doses of 128 J/cm2 in the animal models. In patients, there was no observed UV− skin response at doses of up to 2 mg/kg, drug–light intervals of 1–3 h or greater and light exposures up to 128 J/cm2. At higher drug doses in the rat and pig models, the duration of skin phototoxicity was found to be ∼3 h and less than 1 h, respectively. Using the full spectrum of solar-simulated light, the presence of TOOKAD did not measurably enhance the UV+-induced erythema in the rats, pigs or patients.
    Photochemistry and Photobiology 05/2007; 81(1):106 - 113. · 2.29 Impact Factor
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    ABSTRACT: Ultrasound imaging is proving to be an important tool for medical diagnosis of dermatological disease. Backscatter spectral profiles using high-frequency ultrasound (HFUS, 10-100 MHz) are sensitive to subtle changes in eukaryotic cellular morphology and mechanical properties that are indicative of early apoptosis, the main type of cell death induced following photodynamic therapy (PDT). We performed experiments to study whether HFUS could also be used to discern changes in bacteria following PDT treatment. Pellets of planktonic Staphylococcus aureus were treated with different PDT protocols and subsequently interrogated with HFUS. Changes in ultrasound backscatter response were found to correlate with antimicrobial effect. Despite their small size, distinct changes in bacterial morphology that are indicative of cell damage or death are detectable by altered backscatter spectra from bacterial ensembles using HFUS. This highlights the potential for HFUS in rapidly and non-invasively assessing the structural changes related to antimicrobial response.
    Journal of Biological Physics 03/2007; 33(1):61-6. · 0.95 Impact Factor
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    ABSTRACT: Photodynamic therapy (PDT) using verteporfin is widely used for treatment of age related macular degeneration (AMD). Due to non-perfect selectivity of the drug accumulation in the neovasculature some collateral damage to healthy tissue arises during the treatment. Damage to healthy structures in the eye is always a concern because of a high probability of reducing visual acuity. Two-photon (2-gamma) photodynamic therapy potentially offers much higher treatment selectivity than its one-photon (1-gamma) counterpart. By utilizing focused light for 2-gamma excitation, treatment volumes on the order of microliters can be achieved thus maximizing localized insult to abnormal blood vessels and sparing healthy tissue. We propose that 2-gamma photodynamic therapy will be valuable in the treatment of choroidal neovascularization secondary to age related macular degeneration as well as other conditions. To ascertain feasibility of 2-gamma photodynamic therapy we measured 2-gamma spectrum and cross sections of verteporfin (80 GM at 940 nm, 1 GM = 10-50 cm4s/photon), chlorin e6 (14 GM at 800 nm) and tetrasulfonated aluminum phthalocyanine (140 GM at 900 nm) and investigated their in vitro efficiency under 2-gamma excitation. Only verteporfin demonstrated cell kill under the used irradiation parameters (average light intensity 9.1 mW, wavelength 850 nm, total light dose 6900 J/cm2). Dorsal skinfold window chamber model in mouse was used to test efficiency of 2-gamma PDT with verteporfin in vivo. Although we were able to induce photodynamic damage to a blood vessel using 1-gamma excitation, 2-gamma excitation resulted in no visible damage to irradiated blood vessel. The most probable reason is low efficiency of verteporfin as a 2-gamma photosensitizer. We also report 2-gamma spectrum of new photosensitizer, HCC4 (4300 GM at 830 nm), specifically designed for efficient 2-gamma excitation.
    Proc SPIE 02/2007;
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    ABSTRACT: Imaging modalities facilitate the detection of early bony metastases. Few studies specifically address vertebral metastases in animal models for preclinical (early, asymptomatic) disease. We performed intracardiac injection of human breast cancer (MT-1) cells in 35 athymic nude rats. We evaluated potential temporal differences in appendicular versus axial metastases as detectable by longitudinal in vivo conventional radiography (ie, fine detail radiography and two-dimensional fluoroscopy). We compared bioluminescent reporter imaging with conventional radiographs in the detection of vertebral metastasis, and compared bioluminescent imaging with subsequent ex vivo microcomputed tomography analysis of osteolysis. The mean survival was 25 days in the animals that had metastases develop. Conventional radiographs identified appendicular osteolysis by 14 days; however, vertebral osteolysis was identified late in the metastatic spread (Days 25-28). Bioluminescence imaging was more sensitive in earlier detection of vertebral lesions in all imaged animals at Day 21, which corresponded to microcomputed tomography evaluation of osteolysis. Conventional radiographs do not appear useful for early detection of vertebral metastasis. Early identification of metastasis is important when considering the use of this model to evaluate therapeutic outcomes directed toward vertebral metastasis.
    Clinical Orthopaedics and Related Research 02/2007; 454:230-6. · 2.79 Impact Factor
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    ABSTRACT: Photodynamic therapy (PDT) entails the combination of photosensitizer and light to generate cytotoxic molecules that derive from molecular oxygen (O2). The presence of sufficient O2 within the target tissues is critical to the efficiency of PDT. This study investigates the use of hyperbaric oxygen therapy in combination with PDT (HOTPDT) to augment the photodynamic action of methylene blue (MB) or 5-aminolevulinic acid (ALA) against gram positive and gram negative bacterial strains in vitro. Staphylococcus aureus or Pseudomonas aeruginosa were grown in trypticase soy broth as planktonic cultures (~108/mL) or as established biofilms in 48 well plates (3 days old) at 32°C. Dark toxicity and PDT response in the presence or absence of HOT (2 atmospheres, 100% O2 for 30, 60 or 120 min) was established for both MB (0-0.1 mM) and ALA (0- 1 mM) for a range of incubation times. The number of surviving colonies (CFU/mL) was plotted for each treatment groups. Light treatments (5, 10, 20 or 30 J/cm2) were conducted using an array of halogen bulbs with a red filter providing 90% transmittance over 600-800 nm at 21 mW/cm2. HOT increased the dark toxicity of MB (30 min, 0.1 mM) from 1 and >2 logs of cell kill (CFU/mL) at 5 and 10 J/cm2 light dose respectively as compared to PDT alone. HOT-PDT also increased the anti-microbial effects of MB against Staphylococcus aureus biofilms compared to PDT, albeit less so (> 2 logs) following 10 J/cm2 light dose. Anti-microbial effects of PDT using ALA were not significant for either strain with or without HOT. These data suggest that HOTPDT may be useful for improving the PDT treatment of bacterial infections.
    Proc SPIE 02/2007;
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    ABSTRACT: The concept of metronomic photodynamic therapy (mPDT) is presented, in which both the photosensitizer and light are delivered continuously at low rates for extended periods of time to increase selective tumor cell kill through apoptosis. The focus of the present preclinical study is on mPDT treatment of malignant brain tumors, in which selectivity tumor cell killing versus damage to normal brain is critical. Previous studies have shown that low-dose PDT using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis in either tumor or normal brain tissue or apoptosis in the latter. On the basis of the levels of apoptosis achieved and model calculations of brain tumor growth rates, metronomic delivery or multiple PDT treatments, such as hyperfractionation, are likely required to produce enough tumor cell kill to be an effective therapy. In vitro studies confirm that ALA-mPDT induces a higher incidence of apoptotic (terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate, sodium salt nick-end labeling positive) cells as compared with an acute, high-dose regimen (ALA-aPDT). In vivo, mPDT poses two substantial technical challenges: extended delivery of ALA and implantation of devices for extended light delivery while allowing unencumbered movement. In rat models, ALA administration via the drinking water has been accomplished at very high doses (up to 10 times therapeutic dose) for up to 10 days, and ex vivo spectrofluorimetry of tumor (9L gliosarcoma) and normal brain demonstrates a 3-4 fold increase in the tumor-to-brain ratio of PpIX concentration, without evidence of toxicity. After mPDT treatment, histological staining reveals extensive apoptosis within the tumor periphery and surrounding microinvading colonies that is not evident in normal brain or tumor before treatment. Prototype light sources and delivery devices were found to be practical, either using a laser diode or light-emitting diode (LED) coupled to an implanted optical fiber in the rat model or a directly implanted LED using a rabbit model. The combined delivery of both drug and light during an extended period, without compromising survival of the animals, is demonstrated. Preliminary evidence of selective apoptosis of tumor under these conditions is presented.
    Photochemistry and Photobiology 01/2007; 80:22-30. · 2.29 Impact Factor
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    ABSTRACT: Photodynamic therapy has been successfully applied to numerous cancers. Its potential to treat cancer metastases in the spine has been demonstrated previously in a preclinical animal model. The aim of this study was to test two photosensitizers, benzoporphyrin-derivative monoacid ring A (BPD-MA) and by 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), for their potential use to treat bony metastases. The difference in photosensitizer concentration in the spinal cord and the surrounding tumor-bearing vertebrae was of particular interest to assess the risk of potential collateral damage to the spinal cord. Vertebral metastases in a rat model were generated by intracardiac injection of human breast cancer cells. When tumor growth was confirmed, photosensitizers were injected systemically and the animals were euthanized at different time points. The following tissues were harvested: liver, kidney, ovaries, appendicular bone, spinal cord and lumbar vertebrae. Photosensitizer tissue concentration of BPD-MA or PpIX was determined by fluorescence spectrophotometry. In contrast to BPD-MA, ALA-PpIX did not demonstrate an appreciable difference in the uptake ratio in tumor-bearing vertebrae compared to spinal cord. The highest ratio for BPD-MA concentration was found 15 min after injection, which can be recommended for therapy in this model.
    Photochemistry and Photobiology 01/2007; 83(5):1034-9. · 2.29 Impact Factor
  • Stuart K Bisland, Shane Burch
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    ABSTRACT: Photodynamic therapy (PDT) defines the light activation of a photosensitizing compound, leading to the generation of cytotoxic, reactive oxygen species. We are investigating the unique application of PDT for diseased bone.
    Photodiagnosis and photodynamic therapy. 09/2006; 3(3):147-155.
  • Stuart K. Bisland, Brian C. Wilson
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    ABSTRACT: There have been numerous reports describing the phenomena of low-level light therapy (LLLT) within the clinic and its broad application to alleviate pain, enhance the rate of wound healing, including spinal cord injury, reduce inflammation, improve learning, bolster immunity and combat disease. Yet, despite the breadth of potential applications for which bio-stimulation may prove beneficial, there persists a dramatic ignorance in our understanding of the signal pathways that govern these effects. At the cellular level, there exist a variety of endogenous chromophores such as cytochrome C oxidase, NADPH, FAD, FMN and other factors intrinsic to the electron transport chain in mitochondria that absorb light of specific wavelength and will undoubtedly have their role in bio-stimulation, however the dose dependency of effect with regard to total light fluence and fluence rate, as well as the importance of specific subcellular targeting, remains elusive. Furthermore, the translation of cellular response(s) in vitro to in vivo needs to be expounded. Clearly, a rigorous examination of bio-stimulatory parameters as a function of cellular and tissue response is necessary if we are to attain optimized, reproducible protocols based on a true scientific rationale for using bio-stimulation as a therapeutic modality in clinic. This paper introduces a number of the challenges we now face for advancing the bio-stimulation phenomena into the scientific mainstream by highlighting our current knowledge in this field as well as some of the research that we are conducting using LLLT in combination with photodynamic therapy.
    Proc SPIE 03/2006;
  • Stuart K. Bisland, Brian C. Wilson
    [Show abstract] [Hide abstract]
    ABSTRACT: There have been numerous reports describing the phenomena of low-level light therapy (LLLT) within the clinic and its broad application to alleviate pain, enhance the rate of wound healing, including spinal cord injury, reduce inflammation, improve learning, bolster immunity and combat disease. Yet, despite the breadth of potential applications for which bio-stimulation may prove beneficial, there persists a dramatic ignorance in our understanding of the signal pathways that govern these effects. At the cellular level, there exist a variety of endogenous chromophores such as cytochrome C oxidase, NADPH, FAD, FMN and other factors intrinsic to the electron transport chain in mitochondria that absorb light of specific wavelength and will undoubtedly have their role in bio-stimulation, however the dose dependency of effect with regard to total light fluence and fluence rate, as well as the importance of specific subcellular targeting, remains elusive. Furthermore, the translation of cellular response(s) in vitro to in vivo needs to be expounded. Clearly, a rigorous examination of bio-stimulatory parameters as a function of cellular and tissue response is necessary if we are to attain optimized, reproducible protocols based on a true scientific rationale for using bio-stimulation as a therapeutic modality in clinic. This paper introduces a number of the challenges we now face for advancing the bio-stimulation phenomena into the scientific mainstream by highlighting our current knowledge in this field as well as some of the research that we are conducting using LLLT in combination with photodynamic therapy.© (2006) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
    02/2006;
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    ABSTRACT: Osteomyelitis can lead to severe morbidity and even death resulting from an acute or chronic inflammation of the bone and contiguous structures due to fungal or bacterial infection. Incidence approximates 1 in 1000 neonates and 1 in 5000 children in the United States annually and increases up to 0.36% and 16% in adults with diabetes or sickle cell anaemia, respectively. Current regimens of treatment include antibiotics and/or surgery. However, the increasing number of antibiotic resistant pathogens suggests that alternate strategies are required. We are investigating photodynamic therapy (PDT) as one such alternate treatment for osteomyelitis using a bioluminescent strain of biofilm-producing staphylococcus aureus (S. aureus) grown onto kirschner wires (K-wire). S. aureus-coated K-wires were exposed to methylene blue (MB) or 5-aminolevulinic acid (ALA)-mediated PDT either in vitro or following implant into the tibial medullary cavity of Sprague-Dawley rats. The progression of S. aureus biofilm was monitored non-invasively using bioluminescence and expressed as a percentage of the signal for each sample immediately prior to treatment. S. aureus infections were subject to PDT 10 days post inoculation. Treatment comprised administration of ALA (300 mg kg(-1)) intraperitoneally followed 4 h later by light (635 +/- 10 nm; 75 J cm(-2)) delivered transcutaneously via an optical fiber placed onto the tibia and resulted in significant delay in bacterial growth. In vitro, MB and ALA displayed similar cell kill with > or =4 log(10) cell kill. In vivo, ALA-mediated PDT inhibited biofilm implants in bone. These results confirm that MB or ALA-mediated PDT have potential to treat S. aureus cultures grown in vitro or in vivo using an animal model of osteomyelitis.
    Photochemical and Photobiological Sciences 01/2006; 5(1):31-8. · 2.92 Impact Factor
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    ABSTRACT: Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 +/- 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm2) effectively eradicated SAbiofilms within bone. Conclusions: Results support the application of PDT to the treatment of primary or metastatic lesions within bone. Secondly, that ALA-PDT may be useful as a treatment for osteomyelitis. Further studies aim to optimize the parameters of delivering PDT into bone and explore imaging technologies that can be used for clinical PDT.
    Proc SPIE 01/2006;
  • Stuart K. Bisland, Brian Wilson
    Spine Journal - SPINE J. 01/2006; 6(5).
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    ABSTRACT: The feasibility and efficacy of photodynamic therapy (PDT) for the treatment of vertebral metastases using a minimally invasive surgical technique adapted from vertebroplasty was evaluated in a rodent model. Initial validation included photosensitizer (benzoporphyrin-derivative monoacid-ring A) drug uptake studies and in vitro confirmation of PDT efficacy. Intracardiac injection of human MT-1 breast cancer cells was performed in athymic rats. In 63 rats that developed vertebral metastases 21 days post-inoculation, single treatment of PDT was performed using a parapedicular approach placing an optical fiber adjacent to targeted vertebrae. Two milligrams per kilogram of photosensitizer drug was administered intravenously followed by 150 mW of 690 nm light illumination at varying drug-light intervals and light energies. Histologic and immunohistochemical analysis was performed assessing treatment effect. Local tumor viability and growth was quantified by bioluminescence imaging pre and 48 h post-treatment. PDT demonstrated an ablative effect on vertebral metastases (light energies 25-150 J). The effect varied in proportion to light energy with the greatest anti-tumor effect observed at 150 J using a 3 h drug-light interval. 9/22 rodents in the 3 h drug-light interval developed hindlimb paralysis following treatment, consistent with drug uptake studies demonstrating an increase in spinal cord uptake 3h following drug administration. The observations of paralysis following treatment highlight the importance of closely defining the therapeutic window of treatment in safety and efficacy.
    Journal of Orthopaedic Research 10/2005; 23(5):995-1003. · 2.88 Impact Factor

Publication Stats

598 Citations
84.14 Total Impact Points

Institutions

  • 2009
    • University of California, San Francisco
      • Department of Orthopaedic Surgery
      San Francisco, CA, United States
  • 1999–2009
    • University of Toronto
      • • Sunnybrook Health Sciences Centre
      • • Department of Medical Biophysics
      Toronto, Ontario, Canada
  • 2007
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
    • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
  • 2004–2007
    • University Health Network
      • Division of Biophysics and Bioimaging
      Toronto, Ontario, Canada
  • 2001–2004
    • Ontario Institute for Cancer Research
      Toronto, Ontario, Canada
  • 1994
    • University of Aberdeen
      Aberdeen, Scotland, United Kingdom