在皮下和颅内肿瘤模型中，荧光诊断及光动力疗法联合抗血管生成疗法治疗C6胶质瘤。

Fluorescent diagnosis and photodynamic therapy for C6 glioma in combination with antiangiogenic therapy in subcutaneous and intracranial tumor models.

作者信息

Tzerkovsky D A, Osharin V V, Istomin Y P, Alexandrova E N, Vozmitel M A

机构信息

N.N. Alexandrov National Cancer Center of Belarus, 223040 Minsk, Belarus.

Department of Pathology, N.N. Alexandrov National Cancer Center of Belarus, BY 223040 Lesnoj 2, Minsk, Belarus.

出版信息

Exp Oncol. 2014 Jun;36(2):85-9.

PMID:24980761

Abstract

OBJECTIVE

Investigating the distinctions pharmacokinetics of chlorin e6 conjugated with polyvinyl pyrrolidone photosensitizer (Ce6CPPPS)in healthy and tumor tissues of rat brain and evaluating the antitumor efficacy of combination treatment for C6 rat glioma including photodynamic (PDT) and antiangiogenic therapy (AAT).

MATERIALS AND METHODS

The study was performed on 50 white random-bred rats in subcutaneous and intracranial models of C6 glioma. Photosensitizer (PS) Ce6CPPPS single injection at a dose of 2.5 mg/kg was made into the animal's caudal vein. The PS accumulation level in brain tissues and C6 rat glioma was measured with spectral fluorescence technique using LESA-01-Biospek spectrum analyser (Russian Federation, Moscow; λ = 632.8 nm). Photoirradiation of intracranial and subcutaneous C6 glioma was carried out with a light exposure dose of 50 J/cm(2) (IMAF-Axicon, Republic of Belarus; λ = 661 nm). AAT drug bevacizumab, single injection was made intravenously at a dose of 10 mg/kg 24 h after tumor photoirradiation. The criteria for efficacy evaluation were mean survival time (MST) and median survival of the animals in the study group vs the control and the -percentage of tumor necrosis areas induced by the above-mentioned treatment.

RESULTS

The optimal time for photoirradiation of intracranial C6 glioma is 0.5 h after Ce6CPPPS injection. The combination therapy group demonstrated a statistically significant MST increase (38.4 ± 4.39 days) compared with the PDT group (29.2 ± 3.5 days) (p = 0.02) and the AAT group (27.1 ± 2.74 days) (p = 0.02). Necrosis areas in tumor tissue were as follows: the intact control - 10.0 ± 2.55%, PDT - 54.87 ± 6.95% (p = 0.003), AAT - 57.83 ± 6.53% (p = 0.003) and combination therapy - 89.43 ± 5.57% (p = 0.001).

CONCLUSIONS

This paper is the first report about feasibility of efficient use of PDT with a PS of chlorin series and AAT with bevacizumab for the treatment of brain tumors in experimental models.

摘要

目的

研究氯e6与聚乙烯吡咯烷酮结合的光敏剂（Ce6CPPPS）在大鼠脑健康组织和肿瘤组织中的药代动力学差异，并评估联合治疗C6大鼠胶质瘤的抗肿瘤疗效，包括光动力疗法（PDT）和抗血管生成疗法（AAT）。

材料与方法

对50只白色随机繁殖大鼠进行C6胶质瘤皮下和颅内模型研究。将剂量为2.5mg/kg的光敏剂（PS）Ce6CPPPS单次注入动物尾静脉。使用LESA-01-Biospek光谱分析仪（俄罗斯联邦，莫斯科；λ = 632.8nm）通过光谱荧光技术测量脑组织和C6大鼠胶质瘤中的PS积累水平。对颅内和皮下C6胶质瘤进行光照射，光照剂量为50J/cm²（白俄罗斯共和国IMAF-Axicon；λ = 661nm）。在肿瘤光照射后24小时，静脉内单次注射AAT药物贝伐单抗，剂量为10mg/kg。疗效评估标准为研究组动物与对照组的平均生存时间（MST）和中位生存期，以及上述治疗诱导的肿瘤坏死面积百分比。

结果

颅内C6胶质瘤的最佳光照射时间为Ce6CPPPS注射后0.5小时。联合治疗组的MST较光动力疗法组（29.2±3.5天）（p = 0.02）和抗血管生成疗法组（27.1±2.74天）（p = 0.02）有统计学显著增加（38.4±4.39天）。肿瘤组织中的坏死面积如下：完整对照组 - 10.0±2.55%，光动力疗法组 - 54.87±6.95%（p = 0.003），抗血管生成疗法组 - 57.83±6.53%（p = 0.003），联合治疗组 - 89.43±5.57%（p = 0.001）。