Experimental And Clinical Study Of Spinal Metastases Treatment By PVP With ～(153)Sm-EDTMP Incorporated Into Bone Cement

Objectives1. To evaluate the feasibility of spinal metastases treatment by percutaneous vertebtoplasty with Samarium-153 ethylene diamine tetramethylene phosphonate (¹⁵³Sm-EDTMP) incorporated into bone cement.2. To investigate the mechanism of bone cement leakage to the vein around the vertebra and of pulmonary cement embolism.Methods1. To obtain solid mixture composed of ¹⁵³Sm-EDTMP and barium sulphate, a small quantity of barium sulphate was added into the ¹⁵³Sm-EDTMP solution, then heated up to vaporize water. The mixture was blended with polymethyl meth-acrylate (PMMA) powder first, and ultimately with methyl methacrylate (MMA) to produce bone cement with ¹⁵³Sm-EDTMP.2. ¹⁵³Srn-EDTMP was administered to the vertebra of health mongrel dog at 370 MBq(10 mCi), 740 MBq(20 mCi), 1010 MBq(30 mCi), 1380 MBq(40 mCi) and 1850 MBq(50 mCi),respectively, to determine the range of safety dosage of ¹⁵³Sm-EDTMP in normal tissues. Then the rate of activity of ¹⁵³Sm-EDTMP carried into the vertebra was estimated. Imaging investigation was performed with Single Photon Emission Computerized Tomography (SPECT), Computed Tomography(CT) and Magnetic Resonance Imaging(MRI). The life quality of dog was assessed by following up it for six to eleven months. Then the dog was sacrificed and the specimen of its vertebra was acquired and histologically proven through unaided eyes and optical microscope.3. Using ¹⁵³Sm-EDTMP as a tracer mixing with bone cement, a model of bone cement leakage into para-veins of vertebra and pulmonary cement embolization was established by injecting the mixture of PMMA and MMA into the vertebra of dog at different speed and at the ratio of 1:0.5, 1:0.75 and 1:1, respectively.4. The effect of spinal metastases treatment by PVP with ¹⁵³Sm-EDTMP incorporated into bone cement was observed through a twenty-one-patient control study. Patients' self-evaluations were obtained through a pain questionnaire (rated with a visual analogue scale, VAS) completed by each patient before and after treatment, with the following variables specified: daily analgesic use, subsequent converting to oral morphine equivalent dose, sleep characteristics, level of discomfort on a five-point scale, and a weekly statement on the help of the study in decreasing pain.Results1. The solid mixture composed of ¹⁵³Sm-EDTMP and barium sulphate looked primrose yellow and viscous. It adhered to the wall of ampoule and could be scaled. Only one percent to threepercent activity loss of ⁵³Sm-EDTMP was found when its solution was transformed into solid mixture. Some of the mixture still adhered to the wall ampoule when mixed with PMMA and MMA. The physical quality of bone cement remained unchanged.2. The study showed that 42% to 73% of the primary activity of solid ¹⁵³Sm-EDTMP was carried into the vertebra of dog. CT and MRI revealed that the bone cement configuration and distribution was normal. SPECT found that solid ¹⁵³Srn-EDTMP deposited in the vertebra and amalgamated with bone cement. No normal tissue damnification was found in the activity scope between 10mCi to 50mCi. Neither was systematic radiation injury reaction.3. When the PMMA and MMA ratio was at 1:0.5, 1:0.75, and 1:1, the speed of polymerization reaction slowed down, the mucosity of bone cement dropped, and the injection became easier. Bone cement had already been found leaking into the vertebral para-vein when PMMA and MMA mixture was slowly injected at ratio of 1:1. When the mixture was injected fast, bone cement leakage into the vertebral para-veins could be found more frequent. Pulmonary cement embolization also occurred when the mixture of PMMA and MMA was injected fast at the ratio of 1:0.75 or 1:1.4. After injection, the dosimetry of ¹⁵³Sm-EDTMP carried into the vertebral metastases was calculated between 25.4mCi to 31.6mCi, which was 63.5% to 79.03% of the primary activity before the injection. A comparison between the single PVP groups and active treatment groups was conducted at Month 1, 2, 3, 4, 5, 6, and 7. The VAS data were separately calculated and analyzed. The 70% pain relief rate in single PVP groupswas increased to 91% in active treatment groups, with a mean duration of 6 months. The vertebral function was protected in both groups. Conclusion1. Mixing a small quantity of barium sulphate into the ¹⁵³Srn-EDTMP solution might be a desirable method to obtain solid mixture composed of ¹⁵³Sm-EDTMP and barium sulphate. The solid ¹⁵³Srn-EDTMP has to be mixed with PMMA powder first before interfused with MMA to make liquid bone cement, and consequently being carried into vertebra through PVP.2. Dog experiment indicated that solid ¹⁵³Sm-EDTMP can be carried into vertebra through PVP. Solid ¹⁵³Sm-EDTMP would stay in the bone cement or circumambience without being absorbed into blood. The physical quality of bone cement in the vertebra remained unchanged. The safety dosage of ¹⁵³Sm-EDTMP for injection is between 10mCi to 50mCi. Within this range, no immediate injury to the normal tissues was found. Even though mild injuries occur in the future, it can be repaired by organism automatically. Local ¹⁵³Sm-EDTMP injection would not result in side effects or complications of blood system.3. The model of bone cement leakage into vertebral para-vein and pulmonary cement embolism can be established through changing the ratio of bone cement component and bone cement injection speed. The reduced mucosity of bone cement and the fast injection of it might be the two factors not only inducing bone cement leakage, but also increasing its incidence when they interact with each other. The leakage into vertebral para-vein and pulmonary cement embolism...