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目的预测恶性淋巴瘤(ML)患者的治疗反应,并判断根据甲氧基异丁基异腈(~(99)Tc~m-MIBI)显像参数,能否对多药耐药基因(MDR1)及多药耐药相关蛋白(MRP)基因的表达准确进行功能性评估。方法 23例经淋巴结活检病理证实的 ML 患者,在化疗前均进行~(99)Tc~m-MIBI 显像,分别计算早时像(10 min)和晚时像(1 h)的靶本(T/B)比值以及~(99)Tc~m-MIBI 显影剂的洗脱率(WR%);采用逆转录(RT)-PCR 方法,检测病变淋巴结活体组织标本多药耐药基因 MDR-1及 MRP mRNA 表达水平;在经过6～8个疗程的联合化疗(加或不加局部放疗)后,通过临床和放射学方法对淋巴瘤患者的治疗反应进行评价。结果 MDR1、MRP mRNA 同时表达阴性患者组的 WR%(16±6)明显低于两者同时阳性表达组(33±5)和两者其一阳性表达组(28±6,均 P<0.01);两者同时阳性表达组与两者其一阳性表达组之间差异无统计学意义(P=0.26)。MDR1阳性组早时像 T/B 值、晚时像 T/B 值和WR%分别为3.0±1.1,2.5±0.8,17±7,MDR1阴性组三值分别为3.4±1.0,2.3±0.7,32±6,MDR1阳性组与阴性组相比,在早时像 T/B、晚时像 T/B 差异均无统计学意义(均 P>0.05),但 WR%比较差异有统计学意义(P<0.01);MRP 阳性组三值分别为3.1±1.2,2.5±0.8,19±8,MRP 阴性组分别为3.3±1.0,2.3±0.7,31±6,MRP 阳性与阴性组比较,也仅 WR%差异有统计学意义(P=0.003),而在早时像 T/B、晚时像 T/B 差异均无统计学意义(均 P>0.01)。MDR1表达水平、WR%与治疗反应均有显著相关性(均 P<0.01);MRP 表达水平与治疗反应则无明显相关性(P=0.052)。结论 ~(99)Tc~m-MIBI 作为一种无创性影像学检查手段,能够准确反映 MDR1、MRP 的表达水平和功能状态,并可以预测 ML 患者的化疗疗效,针对性的采取个体化治疗策略,有益于患者的治疗。
Objective To predict the therapeutic response of patients with malignant lymphoma (ML) and to determine whether MDR1 and multi-drug resistance gene (MDR1) can be detected according to the imaging parameters of methoxyisobutylisonitrile (~ (99) Tc ~ m- The drug resistance-related protein (MRP) gene expression accurately functional assessment. Methods Twenty-three patients with ML confirmed by pathological lymph node biopsy performed ~ 99 Tc m-MIBI imaging before chemotherapy, respectively. The patients with ML (10 min) and late (1 h) T / B ratio, and the elution rate of ~ (99) Tc-m-MIBI developer. The multidrug resistance gene MDR-1 was detected by reverse transcriptase-polymerase chain reaction And MRP mRNA expression level; after 6 to 8 courses of chemotherapy (with or without local radiotherapy), clinical and radiological methods to evaluate the response of patients with lymphoma. Results The percentage of WR% (16 ± 6) was significantly lower in MDR1-negative and MRP-mRNA-negative patients than in both positive and negative controls (33 ± 5 and 28 ± 6, P <0.01, respectively) There was no significant difference between the positive expression group and the positive expression group of both (P = 0.26). MDR1-positive group as early as the T / B value, the nighttime like T / B value and WR% were 3.0 ± 1.1,2.5 ± 0.8,17 ± 7, MDR1 negative group of three values were 3.4 ± 1.0,2.3 ± 0.7, 32 ± 6. Compared with the negative group, there was no significant difference in T / B and T / B ratios between the MDR1 positive group and the negative group (all P> 0.05), but there was significant difference between the two groups P <0.01). The three values of MRP positive group were respectively 3.1 ± 1.2, 2.5 ± 0.8 and 19 ± 8, the MRP negative group was 3.3 ± 1.0, 2.3 ± 0.7 and 31 ± 6, respectively. (P = 0.003). However, there was no significant difference in T / B and T / B at early time (all P> 0.01). MDR1 expression level, WR% and treatment response were significantly correlated (all P <0.01); MRP expression level and treatment response was not significantly correlated (P = 0.052). Conclusions ~ (99) Tc m-MIBI is a noninvasive imaging method that can accurately reflect the expression level and functional status of MDR1 and MRP, and can predict the effect of chemotherapy in patients with ML, and take individualized treatment strategies , Beneficial to the patient’s treatment.