Investigation of new biodegradable 32P-chromic phosphate-poly(L-lactide-co-glycolide) seed after intratumor implantation

Objectives 32P-chromic phosphate-poly(L-lactide-co-glycolide) (32P-CP-PLGA),with biodegradable, compatible PLGA(75/25) as control release carrier for 32P-CP particles, is a new seed for brachytherapy of deep seated tumors. The objective of this study was to investigate its physico-chemical property, dynamic structure changes and systemic distribution of 32P-CP particles in tumor-bearing mice after interstitial administration.

Methods 32P-CP-PLGA seeds were prepared via continue co-adhesion and encapsulation of 32P-CP particles by micronized PLGA(75/25,Mo:10000). Tumor models (H22, Balb/c) were assigned randomly into two groups. 32P-CP-PLGA seeds (seeds group, SG) and 32P-CP colloids (colloids group, CG), with radioactivity of 9.25MBq, were adminitrated to the tumor core. SPECT planar imaging was acquired and %ID/g of different organs, radioactivity of residual seeds were calculated after their sacrifice every 3 days. Scaning electron examination was carried out to observe ultrastructure changes of the seed.

Results 32P-CP-PLGA seeds were cylindrical with hardness, apparent radioactivity of (4.5±1.1) N, (9.25±1.85) MBq. The peak %ID/g of the liver, spleen and bone in SG were 1.056%, 0.934% and 0.616%, lower than that in CG (3.528%, 4.115%, 2.127%, P1, P2, P3<0.05). SPECT planar images demonstrate punctiform appearance of 32P in SG and irregular appearance with abnormal liver, spleen visualization in CG. The intratumor effective half-life of 32P was about 12.2d in SG and 9.4d in CG. Swollen volume, increasing number of micropores, tunnels in seeds, existence of released 32P-CP particles adjacent to seeds in the tumor were observed.

Conclusions Biodegradable 32P-CP-PLGA seeds, enjoying higher local dose radiation and longer intratumoral effective half-life than 32P-CP colloid, may hold promise for deep seated tumor brachytherapy.

Research Support National Natural Science Foundation of China(No.81071185