John E, Thakur M L, Wilder S, Alauddin M M, Epstein A L
Dept. of Radiation Oncology and Nuclear Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107.
J Nucl Med. 1994 May;35(5):876-81.
A number of 99mTc-labeled monoclonal antibodies (Mabs) are being evaluated for diagnostic applications. Preparations are carried out using both direct and indirect (bifunctional chelating agent, BFCA) labeling procedures in which nonspecific 99mTc binding has been postulated.
By using the ascorbic acid (AA) reduction mediated direct labeling procedure and diaminotetrathiol (N2S4) as a BFCA method, we examined the role of specific binding sites and aliphatic E amino groups of lysine as nonspecific binding sites for 99mTc.
Labeling yields for the direct and N2S4 "regular" preparations averaged 73% +/- 2.8% and 91% +/- 2%, for the "specific" preparations, 60% +/- 3.5% and 75% +/- 2% and for the "nonspecific" preparations 13% +/- 1.0% and 16% +/- 1% respectively. All preparations were evaluated in tumor-bearing mice. The control and specific preparations permitted excellent scintigraphic visualization of tumors; the percentages of specific preparations in the tumors being 2.1% +/- 0.5% and 3.1% +/- 0.4%, respectively. With nonspecific preparations, tumors were not visualized and the percentages of administered radioactivity per gram of tumor were only 0.9% +/- 0.2% and 0.9% +/- 0.3%, respectively.
In these 99mTc labeling procedures, the amino group-mediated nonspecific binding of 99mTc to Mabs can be as high as 16% and contributes to increased liver uptake and decreased tumor uptake of radioactivity.
多种99mTc标记的单克隆抗体（Mabs）正在接受诊断应用评估。制备过程采用直接和间接（双功能螯合剂，BFCA）标记程序，其中假定存在非特异性99mTc结合。
通过使用抗坏血酸（AA）还原介导的直接标记程序和二氨基四硫醇（N2S4）作为BFCA方法，我们研究了赖氨酸的特异性结合位点和脂肪族ε氨基作为99mTc非特异性结合位点的作用。
直接和N2S4“常规”制剂的标记产率平均分别为73%±2.8%和91%±2%，“特异性”制剂为60%±3.5%和75%±2%，“非特异性”制剂为13%±1.0%和16%±1%。所有制剂均在荷瘤小鼠中进行评估。对照和特异性制剂可实现肿瘤的良好闪烁显像；肿瘤中特异性制剂的百分比分别为2.1%±0.5%和3.1%±0.4%。使用非特异性制剂时，肿瘤未显影，每克肿瘤的给药放射性百分比分别仅为0.9%±0.2%和0.9%±0.3%。
在这些99mTc标记程序中，99mTc通过氨基介导与Mabs的非特异性结合可高达16%，并导致肝脏放射性摄取增加和肿瘤放射性摄取减少。
