Investigation of Newly Prepared Biodegradable 32 P-chromic Phosphate-polylactide-co-glycolide Seeds and Their Therapeutic Response Evaluation for Glioma Brachytherapy.
CONTRAST MEDIA & MOLECULAR IMAGING(2018)
摘要
P-32 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 P-32-CP colloid tends to leak with blind therapeutic area after intratumour injection. We prepared P-32-chromic phosphate-polylactide-co-glycolide (P-32-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 P-32-CP-PLGA brachytherapy for glioma with the integrin alpha v beta 3-targeted radiotracer Ga-68-3PRGD(2) . P-32-CP-PLGA seeds (seed group, SG, 185 MBq) and P-32-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-SPELT imaging, and biodistribution studies were performed at different time points. 'The tumour volume was measured using a caliper, and Ga-68-3PRGD(2 )micro-PET-CT imaging was performed to evaluate the therapeutic effect after P-32 intratumour administration. The delayed release of P-32-CP was observed with biodegradation of vehicle PLGA. Intratumoural effective half-life of P-32-CP in the SG (13.3 +/- 0.3) d was longer than that in the CG (10.4 +/- 10.3) 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 Ga-68-3PRGD(2) 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, P-32-CPPLGA seeds, controlling the release of entrapped P-32-CP particles, are promising for glioma brachytherapy, and Ga-68-3PRGD(2) imaging shows potential for early response evaluation of P-32-CP-PLGA seeds brachytherapy.
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