Radioimmunoimaging of lymphoma in mice with a two-step pretargeting strategy using biotinyled CD45 monoclonal antibody and 188Re-avidin

LI Guiping; ZHENG Wenli; HUANG Baodan; DU Li; QI Yongshuai; HUANG Kai; ZHANG Hui

doi:10.3969/j.issn.1673-4254.2015.08.018

Abstract：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.