~(32)P-磷酸铬-聚L-乳酸粒子植入实验鼠体内降解特性及代谢

目的 观察~(32)P-磷酸铬-聚L-乳酸(~(32)P-CP-PLLA)粒子植入实验鼠体内的降解特性及代谢.方法 KM小鼠72只,采用开腹或经皮穿刺法将~(32)P-CP-PLLA粒子分别植入小鼠肝、腹腔及腿部肌肉,粒子植入前活度为20.44～25.14 kBq,30 d内不同时间处死,取出粒子,取血及主要脏器测~(32)P放射性计数率,计算每克组织的百分剂量率(%ID/g),用扫描电镜动态观察粒子形态变化.SD大鼠5只,肝内植入粒子后代谢笼饲养,每24小时测量粪便及尿液放射性,计算~(32)P30 d排泄率.计量数据以-x±s表示,采用SPSS 13.0软件进行统计分析.结果 KM小鼠体内生物分布显示~(32)P-CP-PLLA 粒子植入后无一发生粒子移位,释出的~(32)PP在重要脏器和组织中放射性分布略高于本底水平.30 d内组织脏器计数率之和呈现阶段性变化:肝组1～5 d各脏器摄取总值极少,6～10 d略增多,11～20 d又趋减少,21～25 d摄取再次增多,达到峰值(622±11)计数/min,26-30 d略有下降;肌肉组变化与肝组相似,唯峰时提前(15 d),且峰值相对较低,为(403±14)计数/min;腹腔组重要脏器摄取呈持续低水平,无明显阶段性变化.粪便和尿液放射性峰值分别出现在第16天和第19天,排泄率分别为(0.82±0.20)%和(0.50±0.23)%,30 d总排泄率分别为4.08%和1.33%.结论 ~(32)P-CP-PLLA粒子作为一种新型治疗恶性肿瘤植入剂,在体内无脏器迁移,粒子呈现阶段性缓慢降解,降解物不具胶体特性,较少通过粪便和尿液排出体外,显示出良好的体内稳定性、靶向定位性和安全性.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

^32P-磷酸铬-聚L-乳酸缓释粒子的制备及其放射性释出和生物分布

目的研制^32P-磷酸铬-聚L-乳酸（CP—PLLA）缓释粒子,探讨不同配比对其理化性能的影响及植入正常小鼠肌肉后的放射性生物分布及作用特点等。方法应用压制法制备^32P-CP—PLLA缓释粒子,比较不同相对分子质量PLLA、不同原料配比制备粒子的体外溶蚀失重率、放射性释出率（RRR）及放射性自吸收系数（RSAC）;采用经皮穿刺法将相同表面活度的^32P-CP—PLLA缓释粒子和^32P-CP胶体植入和注射至正常小鼠小腿肌肉组织,观察小鼠体内放射性生物分布、有效半衰期、作用特点和粒子体内失重率、RRR。用SPSS12．0软件,多个样本均数比较行单因素方差分析,组间两两比较行t检验。结果^32P-CP—PLLA粒子为淡绿色圆柱体,形态圆整,质量及粒子内放射性分布均匀;RSAC受PLLA相对密度影响较小,随PLLA相对分子质量增大而增加;体外RRR随PLLA的相对分子质量逐渐增加而降低,随PLLA和CP胶体质量比增加而增加,比值为3：1时达峰值,然后逐渐降低,同时粒子脆性逐步增加。^32P-CP—PLLA粒子肌肉植入后,体内失重率及RRR缓慢增加,以RRR增加尤为迅速,且释出^32P-CP主要分布于粒子邻近肌肉组织,肝、脾和粒子侧骨骼每克组织百分注射剂量率（％ID／g）值为1．7887,1．6401和1．9470,明显低于胶体组（4．7523,3．9712和4．3174,t均〉2．7,P均〈0．05）,其他脏器％ID／g值极低,峰值与胶体组差异无统计学意义（t均〈0．65,P均〉0．05）,植入靶位有效半衰期达13d。放射性粒子周围弥漫性变性坏死区内未见正常肌肉纤维存在,肝、脾等重要脏器未见明显异常。结论^32P-CP—PLLA通过自身溶蚀降解缓慢释出放射性,有效提高了植入靶位放射性滞留量和有效半衰期,有效射程内具有集中的生物学效应,可增加应用剂量、提高局部生物学效应并减轻对重要脏器的毒性和不良反?     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.