In vitro and in vivo effects of photodynamic therapy on metastatic breast cancer cells pre-treated with zoledronic acid.

Background: Photodynamic therapy (PDT), a non-ionizing, minimally invasive drug-light treatment, has recently been shown to successfully ablate tumor within rat vertebrae with concurrent improvements in bone strength and architecture. The bisphosphonate zoledronic acid (zol), a current drug for patients with skeletal metastases, primarily works by inhibiting osteoclast activity, but direct anti-tumor effects have also been reported. However, it is unknown if or how pre-treatment with zol may alter the tumorcidal effect of PDT.

The benefits of photodynamic therapy on vertebral bone are maintained and enhanced by combination treatment with bisphosphonates and radiation therapy.

Photodynamic therapy (PDT) has been shown to ablate tumors within vertebral bone and yield short-term improvements in vertebral architecture and biomechanical strength, in particular when combined with bisphosphonate (BP) treatment. Longer-term outcomes of PDT combined with current treatments for skeletal metastases are essential to understand its therapeutic potential. The objective of this study is to evaluate the response of vertebrae to PDT after a longer (6-week) time period, alone and combined with previous BP or radiation treatment (RT).

Multimodal μCT/μMR based semiautomated segmentation of rat vertebrae affected by mixed osteolytic/osteoblastic metastases.

Purpose: Multimodal microimaging in preclinical models is used to examine the effect of spinal metastases on bony structure; however, the evaluation of tumor burden and its effect on microstructure has thus far been mainly qualitative or semiquantitative. Quantitative analysis of multimodality imaging is a time consuming task, motivating automated methods. As such, this study aimed to develop a low complexity semiautomated multimodal μCT/μMR based approach to segment rat vertebral structure affected by mixed osteolytic/osteoblastic destruction.

Evaluating the effects of mixed osteolytic/osteoblastic metastasis on vertebral bone quality in a new rat model.

Spinal metastases often show mixed areas of enhanced (osteoblastic) bone growth adjacent to areas of thinning (osteolytic) bone. This study aims to quantitatively characterize bone quality and tumor burden within a new rat model of mixed osteolytic/osteoblastic spinal metastases. Mixed vertebral metastases were analyzed in nude rats 21-days post intracardiac injection of Ace-1 canine prostate cancer cells.

Non-destructive evaluation of the effects of combined bisphosphonate and photodynamic therapy on bone strain in metastatic vertebrae using image registration.

Skeletal metastases most frequently affect the vertebral column and may lead to severe consequences including fracture. Clinical management of skeletal metastases often utilizes a multimodal treatment approach, including bisphosphonates (BPs). Previous work has demonstrated the synergistic potential of photodynamic therapy (PDT) in combination with BP in treating osteolytic disease through structural, histologic, and destructive mechanical testing analyses.

Imaging of specific activation of photodynamic molecular beacons in breast cancer vertebral metastases.

Breast cancer is the second leading cause of cancer-related death in women. Approximately 85% of patients with advanced cases will develop spinal metastases. The vertebral column is the most common site of breast cancer metastases, where overexpression of matrix metalloproteinases (MMPs) promotes the spread of cancer.

Fracture surface analysis to understand the failure mechanisms of collagen degraded bone.

Fracture surface analysis is a powerful technique to investigate bone failure mechanisms. Previously, emu tibiae were endocortically treated with 1 M potassium hydroxide (KOH) solution for 14 days. This treatment caused in situ collagen degradation rather than removal, with no differences in geometrical parameters, but with significant changes in mechanical properties.

Beyond bisphosphonates: photodynamic therapy structurally augments metastatically involved vertebrae and destroys tumor tissue.

Breast cancer patients commonly develop metastases in the spine, which compromises its mechanical stability and can lead to skeletal related events. The current clinical standard of treatment includes the administration of systemic bisphosphonates (BP) to reduce metastatically induced bone destruction. However, response to BPs can vary both within and between patients, which motivates the need for additional treatment options for spinal metastasis.