Balkin Ethan R, Kenoyer Aimee, Orozco Johnnie J, Hernandez Alexandra, Shadman Mazyar, Fisher Darrell R, Green Damian J, Hylarides Mark D, Press Oliver W, Wilbur D Scott, Pagel John M
Radiation Oncology, University of Washington, Seattle, Washington.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Cancer Res. 2014 Oct 15;74(20):5846-54. doi: 10.1158/0008-5472.CAN-14-0764. Epub 2014 Sep 26.
Cerenkov radiation generated by positron-emitting radionuclides can be exploited for a molecular imaging technique known as Cerenkov luminescence imaging (CLI). Data have been limited, however, on the use of medium- to high-energy β-emitting radionuclides of interest for cancer imaging and treatment. We assessed the use of CLI as an adjunct to determine localization of radioimmunoconjugates to hematolymphoid tissues. Radiolabeled (177)Lu- or (90)Y-anti-CD45 antibody (Ab; DOTA-30F11) was administered by tail vein injection to athymic mice bearing disseminated murine myeloid leukemia, with CLI images acquired at times afterward. Gamma counting of individual organs showed preferential uptake in CD45(+) tissues with significant retention of radiolabeled Ab in sites of leukemia (spleen and bone marrow). This result was confirmed in CLI images with 1.35 × 10(5) ± 2.2 × 10(4) p/s/cm(2)/sr and 3.45 × 10(3) ± 7.0 × 10(2) p/s/cm(2)/sr for (90)Y-DOTA-30F11 and (177)Lu-DOTA-30F11, respectively, compared with undetectable signal for both radionuclides using the nonbinding control Ab. Results showed that CLI allows for in vivo visualization of localized β-emissions. Pixel intensity variability resulted from differences in absorbed doses of the associated energies of the β-emitting radionuclide. Overall, our findings offer a preclinical proof of concept for the use of CLI techniques in tandem with currently available clinical diagnostic tools.
由发射正电子的放射性核素产生的切伦科夫辐射可用于一种称为切伦科夫发光成像（CLI）的分子成像技术。然而，关于用于癌症成像和治疗的中高能β发射放射性核素的使用数据有限。我们评估了CLI作为辅助手段来确定放射免疫缀合物在血液淋巴组织中的定位。通过尾静脉注射将放射性标记的（177）镥或（90）钇抗CD45抗体（Ab；DOTA - 30F11）给予患有播散性小鼠髓性白血病的无胸腺小鼠，随后在不同时间采集CLI图像。对各个器官进行γ计数显示，在CD45（+）组织中有优先摄取，放射性标记的Ab在白血病部位（脾脏和骨髓）有显著保留。在CLI图像中得到了证实，对于（90）钇 - DOTA - 30F11和（177）镥 - DOTA - 30F11，分别为1.35×10（5）±2.2×10（4）p/s/cm（2）/sr和3.45×10（3）±7.0×10（2）p/s/cm（2）/sr，而使用非结合对照抗体时两种放射性核素均未检测到信号。结果表明，CLI能够在体内可视化局部β发射。像素强度变异性是由β发射放射性核素相关能量的吸收剂量差异导致的。总体而言，我们的研究结果为将CLI技术与当前可用的临床诊断工具联合使用提供了临床前概念验证。
