title: [Experimental study of CT guided ³²P-CP-PLLA microparticle implantation in the treatment of rabbit VX2 lung tumor].
abstract: OBJECTIVE
  ³²P-chromic phosphate-poly (L-lactic) acid (³²P-CP-PLLA) microparticle is a novel potent brachytherapy implant, which has good biocompatibility and biodegradability. The aim of this study is to investigate the changes of pathology and PET/CT images in VX2 rabbit tumor after treatment with intratumorol administration of ³²P-CP-PLLA microparticles, and to explore the effects and influence of tumor growth and apoptosis related proteins in VX2 lung tumor treatment with ³²P-CP-PLLA microparticles.
  
  
  METHODS
  Twenty-four tumor bearing rabbits were randomly divided into 4 groups (6 in each group). Group 1, 2 and 3 were treated groups; group 4 was the control. Under CT guidance, ³²P-CPPLLA microparticles were implanted into tumors. Low, medium and high treatment doses were 93 MBq (group 1), 185 MBq (group 2) and 370 MBq (group 3), respectively. ¹⁸F-FDG PET/CT was performed at d0, d3, d7 and d14 after intratumoral administration. In the control group, ¹⁸F-FDG PET/CT images were acquired at the same time points but without treatment. The standardized uptake value (SUV) of tumor regions were calculated. After last PET/CT imaging, the rabbits were euthanized and the tumors were removed for histological and immunohistochemical examination. The pathology and the expression of apoptosis related proteins (bcl-2, bax) were compared.
  
  
  RESULTS
  No significant difference of SUVmax was observed between the treatment groups and the control group at d0. At d14, the SUVmax values for group 1, 2 and 3 were 0.80±0.10, 1.1±0.19 and 2.85±0.15, respectively, and were significantly lower than that of the control group (5.61±0.50)(P < 0.05). Significant dose-response relationship was observed in SUVmax between group 1 and group 2, and the SUV values gradually decreased from d7 to d14 after treatment. In group 3, SUVmax gradually increased and reached a peak at d7 then significantly decreased. The SUVmax values of group 3 were significantly lower than those of the control at the same time point (P < 0.05). HE staining found degenerative necrosis at the site was nearby the microparticle. Necrosis became serious increasing with the radioactivity. Inflammatory cell infiltration was rarely seen in tumors treated with 93 MBq or 185 MBq ³²P-CP-PLLA microparticles. In contrast, the necrotic area was surrounded by marked inflammatory cell infiltration in group 3. IHC analysis showed that the expression of bcl-2 in treated groups were lower than those in the control group, and the expression of bax in treated group was higher than those in the control group (P < 0.05). The ratio of bcl-2/bax protein significantly decreased in the treated group (P < 0.05). Dose dependence was seen in the expression of apoptosis related proteins.
  
  
  CONCLUSIONS
  The sustained irradiation of ³²P-CP-PLLA microparticles can direct kill the VX2 tumor cell, thus the glycolysis of which were suppressed. Although the alive tumor cells still presented faraway from the microparticle, the expression of apoptosis related proteins in which were significantly different from the control. Bcl-2 and bax gene were induced to participate in regulation for the apoptosis of VX2 tumor cell by ionizing radiation from ³²P-CP-PLLA microparticles, so that the tumor growth was inhibited.
authors.affiliation: Jiangsu Key Laboratory of Molecular Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine, Nanjing, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Pan
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Yuping
authors.initials: Y
authors.lastname: Xu
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Peilin
authors.initials: P
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001918:Brachytherapy; D017608:Chromium Compounds / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D008297:Male; D010710:Phosphates / Q000627:therapeutic use*; D010761:Phosphorus Radioisotopes / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D011817:Rabbits; D011897:Random Allocation; D014057:Tomography, X-Ray Computed
chemical_list: D017608:Chromium Compounds; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D019788:Fluorodeoxyglucose F18; C509371:chromic (+3) phosphate (1:1), 32P-labeled