Lee F T, Hall C, Rigopoulos A, Zweit J, Pathmaraj K, O'Keefe G J, Smyth F E, Welt S, Old L J, Scott A M
Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, and Centre for PET, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia.
J Nucl Med. 2001 May;42(5):764-9.
Radiolabeling monoclonal antibodies (mAbs) allows the evaluation of biodistribution of constructs in vivo through gamma camera imaging and also permits quantitation of mAb uptake in tumors through biopsy-based counting techniques. The quantitation of radiolabeled mAb uptake in cancer patients is complicated by the attenuation of gamma emissions of routinely used isotopes (e.g., 131I and 111In) and the spatial resolution and sensitivity of gamma cameras.
We used the positron-emitting isotope 124I (half-life [T1/2] = 4.2 d) to label the recombinant humanized anti-colorectal cancer A33 antibody (huA33) and evaluated its biodistribution properties and PET imaging characteristics in BALB/c nude mice bearing SW1222 colorectal xenografts and control colon tumors.
The immunoreactivity of radioconjugate was 78% as determined using the cell-binding Lindmo assay. The apparent association constant was found to be 2.2 x 10(9) M(-1), and the number of antibody binding sites per cell was 371,000. The radioconjugate was found to be stable in serum obtained from mice at various times after injection. Assuming a two-compartment model with a four-parameter fit of mean blood levels, the T1/2alpha was 1.5 h and the T1/2beta was 38.2 h. Excellent tumor uptake was obtained, with maximal uptake reaching 50.0 +/- 7.0 percentage injected dose per gram of tumor by 4 d after injection. Specificity of localization was shown by lack of uptake in control tumor. PET imaging detected antigen-positive tumor by 4 h after injection, and high-resolution images were obtained by 24 h after injection.
In clinical trials using PET, huA33 labeled with 124I has potential for imaging and staging colon tumors and quantifying antibody uptake in colon tumors in vivo.
放射性标记单克隆抗体（mAb）可通过γ相机成像评估构建体在体内的生物分布，还可通过基于活检的计数技术对肿瘤中mAb摄取进行定量。癌症患者体内放射性标记mAb摄取的定量因常规使用的同位素（如131I和111In）的γ射线衰减以及γ相机的空间分辨率和灵敏度而变得复杂。
我们使用正电子发射同位素124I（半衰期[T1/2]=4.2天）标记重组人源化抗结直肠癌A33抗体（huA33），并在携带SW1222结直肠癌异种移植瘤和对照结肠肿瘤的BALB/c裸鼠中评估其生物分布特性和PET成像特征。
使用细胞结合Lindmo试验测定，放射性偶联物的免疫反应性为78%。发现表观结合常数为2.2×10⁹ M⁻¹，每个细胞的抗体结合位点数为371,000。发现放射性偶联物在注射后不同时间从小鼠获得的血清中稳定。假设采用具有平均血药水平四参数拟合的二室模型，T1/2α为1.5小时，T1/2β为38.2小时。注射后4天，肿瘤摄取良好，最大摄取量达到每克肿瘤50.0±7.0%注射剂量。对照肿瘤未摄取显示了定位的特异性。PET成像在注射后4小时检测到抗原阳性肿瘤，并在注射后24小时获得高分辨率图像。
在使用PET的临床试验中，用124I标记的huA33具有对结肠肿瘤进行成像和分期以及在体内定量结肠肿瘤中抗体摄取的潜力。
