Investigation of Newly Prepared Biodegradable 32P-chromic Phosphate-polylactide-co-glycolide Seeds and Their Therapeutic Response Evaluation for Glioma Brachytherapy.

Guoqiang Shao,Xianzhong Liu,Meili Zhao,Yuebing Wang,Peiling Huang,Feng Wang,Zizheng Wang,Jinhua Song

doi:10.1155/2018/2630480

Abstract

32P high-dose rate brachytherapy allows high-dose radiation delivery to target lesions with less damage to adjacent tissues. The early evaluation of its therapeutic effect on tumours is vital for the optimization of treatment regimes. The most commonly used 32P-CP colloid tends to leak with blind therapeutic area after intratumour injection. We prepared 32P-chromic phosphate-polylactide-co-glycolide (32P-CP-PLGA) seeds with biodegradable PLGA as a framework and investigated their characteristics in vitro and in vivo. We also evaluated the therapeutic effect of 32P-CP-PLGA brachytherapy for glioma with the integrin αvβ3-targeted radiotracer 68Ga-3PRGD2. 32P-CP-PLGA seeds (seed group, SG, 185 MBq) and 32P-CP colloid (colloid group, CG, 18.5 MBq) were implanted or injected into human glioma xenografts in nude mice. Scanning electron microscopy (SEM) of the seeds, micro-SPECT imaging, and biodistribution studies were performed at different time points. The tumour volume was measured using a caliper, and 68Ga-3PRGD2 micro-PET-CT imaging was performed to evaluate the therapeutic effect after 32P intratumour administration. The delayed release of 32P-CP was observed with biodegradation of vehicle PLGA. Intratumoural effective half-life of 32P-CP in the SG (13.3 ± 0.3) d was longer than that in the CG (10.4 ± 0.3) d (P < 0.05), with liver appearance in the CG on SPECT. A radioactivity gradient developed inside the tumour in the SG, as confirmed by micro-SPECT and SEM. Tumour uptake of 68Ga-3PRGD2 displayed a significant increase on day 0.5 in the SG and decreased earlier (on day 2) than the volume reduction (on day 8). Thus, 32P-CP-PLGA seeds, controlling the release of entrapped 32P-CP particles, are promising for glioma brachytherapy, and 68Ga-3PRGD2 imaging shows potential for early response evaluation of 32P-CP-PLGA seeds brachytherapy.

Highlights

Glioblastoma multiforme (GBM) accounts for approximately 60% to 70% of malignant gliomas
Basic Characteristics and Biodegradation of 32P-CP-PLGA Seeds. 32P-CP-PLGA seeds are cylindrical with a diameter of (0.9 ± 0.02) mm, length of (1.9 ± 0.2) mm, weight of (1.2 ± 0.15) mg each, hardness of (5.7 ± 1.4) N, and apparent radioactivity of (18.5±3.7) MBq
The release of 32P-CP-PLGA seeds can be divided into the rapid release phase (0∼8 d, phase I), the stable release phase (8∼60 d, phase II), and the disintegration release phase (60 d ∼, phase III) according to time-release curve slope (Figure 1(a))

Summary

Introduction

Glioblastoma multiforme (GBM) accounts for approximately 60% to 70% of malignant gliomas. The prognosis of patients with GBM remains dismal, with a median survival time of less than one year. This poor prognosis primarily reflects the high proliferative, infiltrative, and invasive properties of GBM [1]. Systemic administration of most potentially active drugs is not effective because of failing to cross the blood-brain barrier. Compared with external-beam radiation, brachytherapy has the advantage of delivering high doses of radiation to target sites without subjecting normal tissues to undue radiation and damage [2]. 32P is ideal because of its relatively long halflife of 14.28 day(s), maximum energy of 1.711 MeV, mean range of 3-4 mm in soft tissues, and high relative biological effect Compared with external-beam radiation, brachytherapy has the advantage of delivering high doses of radiation to target sites without subjecting normal tissues to undue radiation and damage [2]. 32P is ideal because of its relatively long halflife of 14.28 day(s), maximum energy of 1.711 MeV, mean range of 3-4 mm in soft tissues, and high relative biological effect

Methods

Results

Conclusion