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

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.

PLGA Nanoparticle-Based Formulations to Cross the Blood–Brain Barrier for Drug Delivery: From R&D to cGMP

“…Similar to MRI, radionuclide imaging has high sensitivity with no tissue-penetration limitations. Several radionuclide compounds have been extensively studied along with PLGA with the goal of formulating a robust nano delivery system [107]. For instance, Wang and colleagues [108] designed PLGA-lipid hybrid nanocarriers for theranostic therapy, encapsulating an anticancer agent in the matrix, while the lipid shell was chelated with indium-111 or yttrium-90 as radiotherapy agents.…”

“…For instance, Wang and colleagues [108] designed PLGA-lipid hybrid nanocarriers for theranostic therapy, encapsulating an anticancer agent in the matrix, while the lipid shell was chelated with indium-111 or yttrium-90 as radiotherapy agents. Shao et al [107] demonstrated the therapeutic effect of 32P-CP-PLGA brachytherapy for glioma with the integrin αvβ3-targeted radiotracer 68Ga-3PRGD2. Press and colleagues [109] demonstrated the cell-type-specific delivery of short interfering RNAs by covalent conjugation of DY-635 fluorescent dye with known hepatobiliary clearance to a PLGA, which allowed them to monitor distribution, uptake, and clearance of short hairpin RNA from the target organ.…”

A Critical Overview of Targeted Therapies for Glioblastoma

“…Radiolabeling can further enhance the assessment of effects of therapy by brain imaging. For example, 32 p (phosphorus-32)-chromic phosphate-polylactide-co-glycolide (32P-CP-PLGA) for controlled release of the isotope, combined with radiotracer 68 Ga-3PRGD 2 , which targets integrin αvβ3 receptors or the tumor as well as neovasculature, has shown promising results of brachytherapy in a rat model of transplanted glioblastoma ( 65 ).…”