NEUTRON-CAPTURE THERAPY OF THE 9L RAT GLIOSARCOMA USING THE P-BORONOPHENYLALANINE-FRUCTOSE COMPLEX
NEUTRON-CAPTURE THERAPY OF THE 9L RAT GLIOSARCOMA USING THE P-BORONOPHENYLALANINE-FRUCTOSE COMPLEX
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DOI：
10.1016/0360-3016(92)90951-d
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发表时间：
1994-10-15
影响因子：
7
通讯作者：
LIU, HB
中科院分区：
文献类型：
--
作者：
CODERRE, JA;BUTTON, TM;LIU, HB
目的：在大鼠脑肿瘤模型中，腹膜内（IP）注射L-p-硼苯丙氨酸（BPA-F）的溶解果糖复合物比胃内（IG）注射L-p-硼苯丙氨酸（BPA）可能产生更高的硼浓度。IP BPA-F的有效性进行了比较，IG BPA在硼中子俘获治疗辐射的9 L大鼠脑肿瘤model.Methods和Materials：在肿瘤和正常组织中的硼积累的时间过程进行了测定，在雄性F344大鼠轴承SC或脑内9 L胶质瘤后，一个单一的IP注射BPA-F。在接种颅内肿瘤后第14天，用以下任一种单剂量照射大鼠：250 kVp X射线;在IG给予BPA后使用Brookhaven医学研究反应堆的热中子束;或在IP注射BPA-F后使用热中子。磁共振成像被用来可视化的肿瘤疤痕，并评估损害正常的大脑在长期survivor.Results：4小时后，IP注射1200毫克/公斤的BPA-F的硼浓度在肿瘤，血液和正常的大脑分别为89.6 +/- 7.6，27.7 +/- 2.8和17.5 +/- 1.5微克B-10/克。在第二次给药后5小时，两次BPA IG给药（每次750 mg/kg，间隔3小时）分别在肿瘤、血液和脑中产生39 +/- 5、12 +/- 1和10 +/- 1 μ g（10）B/g。三组大鼠接受热中子治疗：一组接受IC BPA治疗，两组接受IP BPA-F治疗。三组BNCT中肿瘤的总物理吸收剂量分别为15.5戈伊（IG BPA，n = 12）、17.0戈伊（IP BPA-F，n = 8）和31.5戈伊（IP BPA-F，n = 8）。未治疗对照组的中位生存期为22天。接受22.5戈伊250 kVp X射线治疗的大鼠（n = 23）的中位生存期为35天，其中20%的长期存活者。IG BPA +热中子组中50%的大鼠存活超过1年。接受IP BPA-F +热中子的两组大鼠均存活超过8个月。长期硼中子俘获疗法幸存者的大脑磁共振成像显示，所有动物的肿瘤植入部位都有疤痕。在IP BPA-F高剂量组一只大鼠表现出水肿的证据，一只大鼠表现出充满液体的囊肿取代tumor.Conclusion：使用IP BPA-F有显着改善长期生存相比，IG BPA。在脑内大鼠9 L胶质肉瘤脑肿瘤模型中长期肿瘤控制的高百分比（100%，n = 16），以及在大多数存活动物中对周围正常脑的很少或没有损伤，证明了硼中子捕获疗法产生的实质性治疗增益。
Purpose: Intraperitoneal(IP) injection of the solubilized fructose complex of L-p-boronophenylalanine (BPA-F) produced higher boron concentrations in a rat brain tumor model than was possible using intragastric (IG) administration of L-p-boronophenylalanine (BPA). The effectiveness of IP BPA-F was compared to IG BPA in boron neutron capture therapy irradiations of the 9L rat brain tumor model.Methods and Materials: The time course of boron accumulation in tumor and normal tissues was determined in male F344 rats bearing either SC or intracerebral 9L gliosarcomas following a single IP injection of BPA-F. On day 14 after inoculation of intracranial tumors, rats were irradiated with single doses of either: 250 kVp X rays; the thermal neutron beam of the Brookhaven Medical Research Reactor following IG administration of BPA; or thermal neutrons following IP injection of BPA-F. Magnetic resonance imaging was used to visualize the tumor scars and to assess damage to the normal brain in long-term survivors.Results: 4 h after IP injection of 1200 mg/kg of BPA-F the boron concentrations in tumor, blood, and normal brain were 89.6 +/- 7.6, 27.7 +/- 2.8 and 17.5 +/- 1.5 mu g B-10/g, respectively. Two IG doses of BPA (750 mg/kg each, 3 h apart) produced 39 +/- 5, 12 +/- 1 and 10 +/- 1 mu g(10)B/g in tumor, blood and brain, respectively at 5 h after the second dose. Three groups of rats were treated with thermal neutrons: one following IC BPA and two groups following IP BPA-F. The total physical absorbed doses to the tumor in the three BNCT groups were 15.5 Gy (IG BPA, n = 12), 17.0 Gy (IP BPA-F, n = 8), and 31.5 Gy (IP BPA-F, n = 8), respectively. The median survival of the untreated controls was 22 days. The median survival of the rats treated with 22.5 Gy of 250 kVp X rays (n = 23) was 35 days with 20% long-term survivors. Fifty percent of the rats in the IG BPA + thermal neutrons group survived over 1 year. All rats in both groups that received IP BPA-F + thermal neutrons have survived over 8 months. Magnetic resonance imaging of the brains of the long-term boron neutron capture therapy survivors showed a scar at the site of tumor implantation in all animals. In the IP BPA-F high-dose group one rat showed evidence of edema and one rat showed a fluid-filled cyst replacing the tumor.Conclusion: The use of IP BPA-F has significantly improved long-term survival compared to IG BPA. The high percentage of long-term tumor control (100%, n = 16) in the intracerebral rat 9L gliosarcoma brain tumor model, together with little or no damage to the surrounding normal brain in the majority of surviving animals, demonstrate the substantial therapeutic gain produced by boron neutron capture therapy.