Clinical Outcome of a Novel Photodynamic Therapy Technique Using Acridine Orange for Synovial Sarcomas¶

Kusuzaki, Katsuyuki; Murata, Hiroaki; Matsubara, Takehiro; Miyazaki, Shinichi; Shintani, Ken; Seto, Masashi; Matsumine, Akihiko; Hosoi, Hajime; Sugimoto, Tsutomu; Uchida, Atsushi

doi:10.1562/2004-06-27-ra-218.1

Cited by 33 publications

(11 citation statements)

References 25 publications

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“…These protons pump out the extracellular fluid or lysosomal fluid, mediated by the actions of the vacuolar-ATPases. Utilizing all of these characteristics of AO revealed by our basic studies, we have developed a technique of photodynamic therapy using AO and have applied it to clinical cases of human musculoskeletal sarcomas; we have demonstrated an excellent clinical outcome of this technique in terms of inhibiting local recurrence and preserving limb function after intra- or marginal tumor resection [5,6,7]. …”

Section: Discussionmentioning

confidence: 99%

“…At present, we apply photodynamic therapy to surgery for musculoskeletal sarcomas by local administration of 1.0 µg/ml of AO solution. In this clinical study, over the last 7 years, none of the patients has developed any local or systemic complications [5,6,7]. It was speculated that AO might induce carcinogenesis, because of its reported mutagenic activity in bacteria [33, 34].…”

Section: Discussionmentioning

confidence: 99%

“…We had previously reported the development and clinical application of photodynamic therapy with AO after intralesional tumor excision to clinical cases of high-grade musculoskeletal sarcoma, with a low frequency of local recurrence and excellent recovery of limb function [5,6,7]. AO also has the ability to specifically accumulate in malignant tumors and to emit brilliant green fluorescence with blue light excitation (fluorovisualization effect) [8,9,10].…”

Section: Introductionmentioning

confidence: 99%

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Extracorporeal Photodynamic Image Detection of Mouse Osteosarcoma in Soft Tissues Utilizing Fluorovisualization Effect of Acridine Orange

Satonaka¹,

Kusuzaki²,

Matsubara³

et al. 2006

Oncology

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Various imaging methods have been employed for the extracorporeal detection of malignant tumors in the human body, such as scintigraphy and PET; however, none is sufficiently accurate and all are also very expensive. To resolve these issues, we attempted to develop a new imaging technique of photodynamic diagnosis (PDD) with acridine orange (AO). AO has the ability to rapidly and specifically accumulate in malignant tumors and emit brilliant green fluorescence after blue light excitation. In this study, we investigated the feasibility of PDD utilizing the fluorovisualization effect of AO, for the extracorporeal detection of mouse osteosarcoma inoculated into the soft tissues. At 2 h after intravenous administration of 0.1, 0.2, 0.5, 1.0, 2.0 and 5.0 mg/kg AO, the tumor and the surrounding normal tissues were illuminated by blue light. The visual fluorescence contrast and ratio (X) of the difference in fluorescence intensity between the tumor and the surrounding normal tissues were evaluated using a high-resolution digital camera equipped with an absorption filter. In addition, the fluorescence contrast was also detected sequentially at 0.5, 1, 2, 3, 6 and 12 h after intravenous administration of AO at 1.0 mg/kg. The results revealed that the optimal condition for clear detection of the tumor was evaluation 2 h after intravenous injection of AO at 0.1 mg/kg, because it provided the best visual contrast on the digital images, and the fluorescence intensity as well as the value of X were higher as compared to the values under other conditions of dose and timing. Based on the results of an acute toxicity study of AO, the estimated LD₅₀ of this substance following intravenous administration was 27.30 mg/kg. In conclusion, we believe that PDD using AO administered intravenously may be feasible for the detection of human musculoskeletal sarcomas in the soft tissues at extremities, and this technique might be a less invasive, less expensive, quicker and more accurate imaging modality than other previously reported imaging methods for this purpose.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Extracorporeal Photodynamic Image Detection of Mouse Osteosarcoma in Soft Tissues Utilizing Fluorovisualization Effect of Acridine Orange

Satonaka¹,

Kusuzaki²,

Matsubara³

et al. 2006

Oncology

Self Cite

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“…Furthermore, in the last 20 years, a combined technique of PDT and radioactivation (RDT) of acridine orange has been successfully developed and applied to clinical cases, demonstrating excellent outcomes in terms of inhibition of local recurrence and preservation of limb function after intra-or marginal tumour resection. These studies include humans affected by bone sarcomas, although the same type of approach has been tested in companion animals with spontaneous fibrosarcoma [158][159][160][161][162]. Specifically, following marginal or even intralesional gross removal of the tumour, it was possible to selectively target residual sarcoma and spare the surrounding normal tissues, with a satisfactory functional result.…”

Section: Targeting Of Cancer Cell Lysosomes By Photodynamic Therapymentioning

confidence: 99%

Acid Microenvironment in Bone Sarcomas

Pompo

Cortini

Baldini

et al. 2021

Cancers

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In bone sarcomas, extracellular proton accumulation is an intrinsic driver of malignancy. Extracellular acidosis increases stemness, invasion, angiogenesis, metastasis, and resistance to therapy of cancer cells. It reprograms tumour-associated stroma into a protumour phenotype through the release of inflammatory cytokines. It affects bone homeostasis, as extracellular proton accumulation is perceived by acid-sensing ion channels located at the cell membrane of normal bone cells. In bone, acidosis results from the altered glycolytic metabolism of bone cancer cells and the resorption activity of tumour-induced osteoclasts that share the same ecosystem. Proton extrusion activity is mediated by extruders and transporters located at the cell membrane of normal and transformed cells, including vacuolar ATPase and carbonic anhydrase IX, or by the release of highly acidic lysosomes by exocytosis. To date, a number of investigations have focused on the effects of acidosis and its inhibition in bone sarcomas, including studies evaluating the use of photodynamic therapy. In this review, we will discuss the current status of all findings on extracellular acidosis in bone sarcomas, with a specific focus on the characteristics of the bone microenvironment and the acid-targeting therapeutic approaches that are currently being evaluated.

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“…169 An analogous but less potent effect is seen with the structurally similar methylene blue. 170 The use of acridine orange has advanced to initial clinical trials [171][172][173][174] and shows promise in sarcomas and other cancers. These effects likely come from Cherenkov light, although other damage effects may also be involved such as complementary biological insult unrelated to optical excitation of the molecule.…”

Section: Molecular Therapy Applications Using X-ray-optical Interactionsmentioning

confidence: 99%

Optical and x-ray technology synergies enabling diagnostic and therapeutic applications in medicine

Pogue

Wilson

2018

J. Biomed. Opt.

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X-ray and optical technologies are the two central pillars for human imaging and therapy. The strengths of x-rays are deep tissue penetration, effective cytotoxicity, and the ability to image with robust projection and computed-tomography methods. The major limitations of x-ray use are the lack of molecular specificity and the carcinogenic risk. In comparison, optical interactions with tissue are strongly scatter dominated, leading to limited tissue penetration, making imaging and therapy largely restricted to superficial or endoscopically directed tissues. However, optical photon energies are comparable with molecular energy levels, thereby providing the strength of intrinsic molecular specificity. Additionally, optical technologies are highly advanced and diversified, being ubiquitously used throughout medicine as the single largest technology sector. Both have dominant spatial localization value, achieved with optical surface scanning or x-ray internal visualization, where one often is used with the other. Therapeutic delivery can also be enhanced by their synergy, where radiooptical and optical-radio interactions can inform about dose or amplify the clinical therapeutic value. An emerging trend is the integration of nanoparticles to serve as molecular intermediates or energy transducers for imaging and therapy, requiring careful design for the interaction either by scintillation or Cherenkov light, and the nanoscale design is impacted by the choices of optical interaction mechanism. The enhancement of optical molecular sensing or sensitization of tissue using x-rays as the energy source is an important emerging field combining x-ray tissue penetration in radiation oncology with the molecular specificity and packaging of optical probes or molecular localization. The ways in which x-rays can enable optical procedures, or optics can enable x-ray procedures, provide a range of new opportunities in both diagnostic and therapeutic medicine. Taken together, these two technologies form the basis for the vast majority of diagnostics and therapeutics in use in clinical medicine.

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Clinical Outcome of a Novel Photodynamic Therapy Technique Using Acridine Orange for Synovial Sarcomas¶

Cited by 33 publications

References 25 publications

Extracorporeal Photodynamic Image Detection of Mouse Osteosarcoma in Soft Tissues Utilizing Fluorovisualization Effect of Acridine Orange

Extracorporeal Photodynamic Image Detection of Mouse Osteosarcoma in Soft Tissues Utilizing Fluorovisualization Effect of Acridine Orange

Acid Microenvironment in Bone Sarcomas

Optical and x-ray technology synergies enabling diagnostic and therapeutic applications in medicine

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