Local treatment of mixed osteolytic/osteoblastic spinal metastases: is photodynamic therapy effective?

Abstract

The widespread use of systemic and local therapies aimed at spinal metastatic lesions secondary to breast cancer has increased the incidence of mixed osteolytic/osteoblastic patterns of bony disease. The complex structure of these lesions requires novel therapeutic approaches to both reduce tumor burden and restore structural stability. In photodynamic therapy (PDT), a minimally invasive approach can be used to employ light to activate a photosensitizing agent that preferentially accumulates in tumor tissue, leading to cell toxicity and death. Previous work in an osteolytic rat model (MT-1) demonstrated that PDT effectively ablates tumor and improves vertebral structural properties. The aim of this study was to assess the efficacy of PDT in a rat model of mixed osteolytic/osteoblastic spinal metastases. Mixed spinal metastases were generated through intracardiac injection of Ace-1 canine prostate cancer cells into female athymic rats (day 0). A single PDT treatment was applied to lumbar vertebra L2 of tumor-bearing and healthy control rats (day 14). PDT-treated and untreated control rats were euthanized and excised spines imaged with μCT to assess bone quality (day 21). Spines were mechanically tested or histologically processed to assess mechanical integrity, tumor burden, and remodelling properties. Untreated tumor-bearing vertebrae showed large areas of osteolysis and areas of immature, new bone formation. The overall bone quality resulting from these lesions consisted of decreased structural properties but without a significant reduction in mechanical integrity. PDT was shown to significantly decrease tumor burden and osteoclastic activity, thereby improving vertebral bone structural properties. While non-tumor-bearing vertebrae exhibited significantly more new bone formation following PDT, the already heightened level of new bone formation in the mixed tumor-bearing vertebrae was not further increased. As such, the effect of PDT on mixed metastases may be more influenced by suppression of osteoclastic resorption as opposed to the triggering of new bone formation.

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

“…While BPs are known to inhibit and induce apoptosis in osteoclasts, the osteoclasts may return to physiologically normal levels 7 weeks after a BP single injection. Similarly, it has been shown that PDT decreases osteoclast activity, particularly in metastatically‐involved vertebrae observed at 1 week post‐PDT treatment . However, local PDT likely would not continue to affect osteoclast proliferation/presence 6 weeks post‐PDT treatment, resulting in the restoration of physiologically normal levels of osteoclasts as seen in this study.…”

“…In Wistar rats, trends towards enhancement in both bone architecture and strength were found 1 week after PDT, with significant improvement 6 weeks post‐treatment . Further study in young athymic rats, a model necessary for the establishment of skeletal metastasis, demonstrated benefits of PDT in osteolytic and mixed osteolytic/osteoblastic vertebral metastases . Combined treatment of BP with PDT had an even more profound effect on enhancing bone structure and strength in osteolytic vertebrae, at one week post‐treatment .…”

Functionalizing NaGdF4:Yb,Er Upconverting Nanoparticles with Bone-Targeting Phosphonate Ligands: Imaging and In Vivo Biodistribution

“…In this work, we explored the potential of phosphonate-functionalized NaGdF 4 :Yb,Er UCNPs to behave as MRI and PET imaging tools for bones, motivated by the long-term prospect of designing theranostic nanoconstructs for the photoactivated delivery of metal-based drugs. Actually, recent results highlight the possibility of adopting photodynamic therapy and related strategies for the treatment of spinal metastases [11] and to ablate tumors within vertebral bone [12]. Therefore, phosphonate ligands were selected for functionalization of UCNPs because of their capacity of accumulating in bones.…”

Spinal metastasis subjected to photodynamic therapy: an update.

“…Previous evidence from animal models has shown that light travels within tumour-involved bone with minimal obstruction from the surrounding cortical bone. In fact, non-involved cortical bone may act as a barrier to prevent light travelling to the spinal cord [11][12][13][14][15][16][17][18][19] . • Delivery of light to the target tissue:°…”