THE EFFECT OF PHOTODYNAMIC THERAPY ON RAT VERTEBRAE

Abstract

Photodynamic therapy (PDT) is a promising new treatment for spinal metastases; however, the effects of PDT on bone are largely unknown. This study assessed the impact of PDT on spinal stability in rats at high (non-therapeutic) drug and LASER light doses. Spinal stability was assessed using stereological measures attained from in vitro μCT scans. High doses of PDT were shown to cause a reduction in vertebral density. Postoperative paralysis was also noted in a subset of animals treated. Tumour-involved vertebrae are already mechanically weakened; as such it is essential to establish a safe and efficacious therapeutic window for vertebral PDT.

This study assessed the effect of high doses of photodynamic therapy (PDT) on biomechanical stability and bone density of lumbar vertebrae.

PDT can cause damage to the vertebral bone and induce paralysis when treatment is applied at very high doses in the rat spine.

PDT is a promising new treatment for spinal metastases however, it is important to understand its effect on vertebral bone in order to closely define the therapeutic window for safety and efficacy.

Trabecular bone density decreased from L1–L3 in normal, untreated rats. The L2 vertebra when treated with high dose PDT was shown to have decreased bone density as compared to both L1 and L3. As expected, tumour-bearing rats had lower vertebral densities than normals.

Rnu/Rnu rats were separated into normal controls, normals treated with PDT and tumour-bearing rats. Rats treated with PDT received an intercardiac injection of 2.5mg/Kg BPD-MA. The drug was activated through administration of 500J (300mA) of a non-thermal 690nm LASER adjacent to the L2 vertebral body. After one week, in vitro μCT scans were taken of L1–L3 and stereological quantities measured.

The demonstrated reduction of bone density as quantified one week following treatment is important when considering spinal stability in the potential use of PDT to treat vertebral metastases. We have observed that the therapy can induce paralysis when treatment is applied at high doses in the rat spine. The intermediate and long-term effects of PDT on bone remain unknown and require ongoing study.