摘要：
Objective To establish a two-step pretargeting approach to lymphoma radioimmunoimaging in mice using biotinynaled CD45 monoclonal antibody (McAb) and 18 Re-avidin in a tumor-bearing mouse model. Methods Six Nod-Scid mice bearing lymphoma cell xenograft were randomized to receive either an intravenous injection of 50μg/200μL biotinyled CD45 McAb followed 24 h later by an intraperitoneal injection of 3.7 MBq (50μg/100μL) 18 Re-avidin (two-step pretargeting group), or a single intravenous injection of 3.7 MBq (100μg/100μL) 18 Re-CD45 McAb (control group). SPECT was performed at 0.5, 1, 6 and 23 h post-injection to characterize 18 Re isotope biodistribution. At 24 h pos-injection, the mice were sacrificed for measurement of radioactivity uptake in the tumor and normal tissues and calculation of the tumor-to-non-tumor (T/NT) ratios. Results SPECT showed that the two-step pretargeting method resulted in a low radioactivity in the blood pool during the imaging and a concentrated radioactivity in the liver and spleen. The transplanted tumor began to be displayed at 1 h post-injection and was clearly displayed at 1-6 h;the images were clear even at 23 h. With the two-step pretargeting method, the radioactive uptake at 24 h post-injection were (1.34±0.52)%, (6.77±2.32)%, and (2.81±1.25)%in the tumor, kidney and liver, respectively, with low radioactivity levels in other organs and high tumor/blood and tumor/muscle ratios (4.28±0.82 and 8.00± 0.88, respectively). In the control group, SPECT revealed intense radioactivity in the liver, spleen, and kidneys with obscure display of the tumor;at 20 h, the radioactivity in the blood pool remained high but that in the tumor was low, and the tumor/blood and tumor/muscle ratios at 24 h were only 0.58±0.06 and 3.21±0.24, respectively. Conclusion Compared with 18 Re-CD45 McAb, the two-step pretargeting approach exhibits a good specificity in targeting lymphoma with an increased T/NT ratio in mice and allows early tumor display at 1 h post-injection.%目的 建立CD45单抗介导的188Re-亲和素二步法预定位方法,观察其在荷瘤小鼠体内的生物学分布特点,评价其在淋巴瘤治疗应用中的可行性.方法 CD45单抗及亲和素的188Re标记采用直接标记法,纸层析法测定标记率及放化纯度.取人Raji细胞移植瘤Nod-Scid小鼠6只,随机分为2组,实验组为二步法预定位组,对照组为188Re-CD45单抗组.注药后0.5、1、6和23 h分别进行SPECT显像;同时于注药后24 h分别处死2组荷瘤小鼠,取脏器组织及肿瘤,称重,测量放射性计数,经放射性衰变校正后计算各脏器%ID/g和靶/非靶(T/NT)比值.结果 188Re-CD45单抗的标记率(82.52±2.92)%,放化纯度>90%;188Re-亲和素标记率平均为(80.83±3.48)%.荷瘤小鼠SPECT显像及体内生物分布结果示:在实验组整个显像期间血池内放射性均较低,肝脏和脾脏内见较多放射性浓聚,注射后1h移植肿瘤见显影,随着时间的延长瘤内放射性分布增多,1~6h肿瘤显影渐清晰,并持续到23 h;注射标记物后24 h,肿瘤摄取(%ID/g)为(1.34±0.52)%,肾脏和肝脏摄取(%ID/g)分别为(6.77±2.32)%和(2.81±1.25)%,其他脏器内的%ID/g保持在较低水平,24 h肿瘤/血液比值为(4.28±0.82),肿瘤/肌肉比值为(8.00±0.88).而对照组则可见肝脏、脾脏和肾脏内有明显放射性聚集,肿瘤部位显影模糊,20 h血池内仍见有较多放射性分布,肿瘤部位见少量放射性集聚;注射标记物后24 h,肿瘤/血液比值为(0.58±0.06),肿瘤/肌肉比值为(3.21±0.24).结论 与188Re-CD45单抗组相比较,CD45单抗介导的188Re-亲和素二步法预定位组在淋巴瘤荷瘤小鼠体内具有较好的特异性和靶向性,明显提高肿瘤的T/NT比值,标记物注射后1 h即可使肿瘤显影.
