Abstract
AIMS: The aim of this study was to investigate the safety and toxicity of biodegradable (32)P-chromic phosphate-poly L lactic acid ((32)P-CP-PLLA) particles interstitially implanted into Beagle dog livers. METHODS: Eighteen healthy Beagle dogs were randomly divided into 6 groups (n=3), and were treated with drugs of different formulations or doses, as well as controls. At different time points after surgery, the experimental dogs were weighed. Detection of indicators of blood chemistry and liver fibrosis, SPECT bremsstrahlung imaging, computed tomography, histological examination, continuous blood measurement, and counting of urine and fecal radioactivity were performed for these dogs. RESULTS: SPECT imaging showed that after implantation of radioactive particles into livers, radioactivity continuously accumulated in the implanted sites, while no radioactivity imaging was found in the nonimplantation sites. The mean absorbance doses in the implantation sites were 89.8-178.7 Gy. Local spherical lesions were observed in tissues. The average effective half-life time of (32)P-CP-PLLA was 11.8 days. Within 4 weeks after surgery, slight or moderate swelling and degradation of liver cells were detected, while in 8 weeks after surgery, they are normal. For the blood chemistry, liver fibrosis, and other indicators, no significant differences were found between the control groups and particle implantation groups (F=1.378, p=0.232). CONCLUSIONS: (32)P-CP-PLLA particles have advantages including good targeting, immobile, being degradable in vivo, easy to be protected, and so on. It is suitable for treating solid tumors with blood supply. (32)P-CP-PLLA particles are a kind of safe, novel, radioactive implantation drug.