A new therapeutic proposal for inoperable osteosarcoma: Photodynamic therapy

Photodiagnosis Photodyn Ther. 2018 Mar:21:79-85. doi: 10.1016/j.pdpdt.2017.11.009. Epub 2017 Nov 22.

Abstract

Background: Osteosarcoma, a malignant tumor characterized by bone or osteoid formation, is the second most common primary bone neoplasm. Clinical symptoms include local and surrounding pain, unrelieved by rest or anesthesia. Osteosarcoma has a poor chemotherapeutic response with prognosis dependent on complete tumor excision. Therefore, for inoperable osteosarcoma new therapeutic strategies are needed. The present study aimed to develop murine models of cranial and vertebral osteosarcoma that facilitate simple clinical monitoring and real-time imaging to evaluate the outcome of photodynamic therapy based on a previously developed photosensitizer.

Methods: Balb/c nude mice were divided into two groups: the cranial and vertebral osteosarcoma groups. Each group was further subdivided into the photodynamic therapy-treated and untreated groups. Images were obtained by scintigraphy with 99mTc-MIBI and radiography. Tumor growth, necrotic area, osteoid matrix area, and inflammatory infiltration were analyzed.

Results: Cranial and vertebral tumors could be macroscopically observed and measured. Radiographic and scintigraphic images showed tumor cells present at the inoculation sites. After photodynamic therapy, scintigraphy showed lower tumoral radiopharmaceutical uptake, which correlated histologically with increased necrosis. Osteoid matrix volume increased, and tumor size decreased in all photodynamic therapy-treated animals.

Conclusion: Cranial and vertebral osteosarcoma models in athymic mice are feasible and facilitate in vivo monitoring for the development of new therapies. Photodynamic therapy is a potential antitumoral treatment for surgically inoperable osteosarcoma.

Keywords: Animal model; Osteosarcoma; Photodynamic therapy; Scintigraphy; Technetium (99m)Tc-MIBI; Xenograft model antitumor assays.

MeSH terms

  • Animals
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / pathology
  • Photochemotherapy / methods*
  • Photosensitizing Agents / therapeutic use*
  • Porphyrins / therapeutic use*
  • Radionuclide Imaging
  • Skull / pathology
  • Spine / pathology

Substances

  • Photosensitizing Agents
  • Porphyrins