Therapeutic effect of biodegradable 32P-chromic phosphate-poly(l-lactide) seeds on human hepatocellular carcinoma in nude mice after intratumoral implantation

Objectives 32P-chromic phosphate-poly(l-lactide) (32P-CP-PLLA), a new biodegradable seed with PLLA as the matrix for 32P-CP microparticles, can achieve high concentration and long retention period of 32P in solid tumors with minimal systemic distribution. The objective of this study was to investigate therapeutic effects of 32P-CP-PLLA seeds on human hepatocellular carcinoma in nude mice.

Methods Human hepatocellular carcinoma (HepG2)-bearing models were established. 32P-CP-PLLA seeds (seeds group, SG) and 32P-CP colloids (Colloids group, CG), with activity of 4.63, 9.25, 18.5 and 37MBq, were administrated to the core of tumors. SG (0 MBq) was the control group. Tumor volume, Survival time and 8wk Survival rate were calculated. The tumors and surrounding tissues were collected for histopathologic analysis. Response was evaluated by the change in tumor volume, histopathology and survival time.

Results Greater reduction in tumor volume was seen in both SG and CG though relapse was found in SG(4.63 MBq) and CG. The complete response rate and survival rate at week 8 in SG were higher than or with no significance with that in CG with same radioactivity. 9.25MBq and 18.5MBq SG showed better prognosis with same complete response rate and 8 wks survival rate(100% and 90%). Complete response rate in 4.63 MBq SG and survival rate in 37MBq SG were lower than that in 9.25MBq and 18.5MBq SGs (P1<0.05,P2<0.01).

Conclusions 32P-CP-PLLA seeds was effective in brachytherapy of solid tumors with regular 32P distritution. The radioactivity ranging from 9.25MBq to 18.5MBq is preferrable with high complete response and survival rate.

Research Support National High Technology Research and Development Program of China (863 Program) (No. 2007AA02Z471) and a grant from the National Natural Science Foundation of China(No. 30670588