Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first—to our knowledge—method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer. Methods: Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with ¹¹¹In to allow SPECT imaging. ¹¹¹In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non–p53-specific ¹¹¹In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells. Results: In vivo SPECT imaging showed enhanced uptake of ¹¹¹In-anti-p53-TAT, versus ¹¹¹In-mIgG-TAT, in high-expression p53^R175H and medium-expression wild-type p53 but not in null p53 tumor xenografts. The results were confirmed in mice bearing genetically engineered KPC mouse–derived pancreatic ductal adenocarcinoma tumors. Imaging with ¹¹¹In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53^R172H pancreatic ductal adenocarcinoma tumors. Conclusion: We demonstrate the feasibility of noninvasive in vivo molecular imaging of p53 in tumor tissue using a radiolabeled TAT-modified monoclonal antibody.

p53 蛋白突变发生在超过一半的癌症中，对肿瘤生物学产生深远影响。我们提出了第一种据我们所知，在 3 种不同的癌症模型中使用 SPECT 对体内肿瘤组织中 p53 进行无创可视化的方法。方法：将抗 p53 单克隆抗体与细胞穿透性反式转录激活因子 （TAT） 肽和金属离子螯合剂偶联，然后用 ¹¹¹In 进行放射性标记以进行 SPECT 成像。¹¹¹ 元In-anti-p53-TAT 偶联物在过表达 p53 特异性细胞中的比非 p53 特异性 ¹¹¹In-mIgG（来自小鼠血浆的小鼠 IgG）-TAT 对照细胞中的保留时间更长，但在无效 p53 细胞中保留的时间更长。结果：体内 SPECT 成像显示，在高表达 p53^R175H 和中表达野生型 p53 中，¹¹¹种 In-anti-p53-TAT 的摄取增加，而在 ¹¹¹种 In-mIgG-TAT 中，但在无效的 p53 肿瘤异种移植物中没有。结果在携带基因工程 KPC 小鼠来源的胰腺导管腺癌肿瘤的小鼠中得到证实。在携带自发性 p53^R172H 胰腺导管腺癌肿瘤的 KPC 小鼠中，可以使用 ¹¹¹个抗 p53-TAT 进行成像。结论：我们证明了使用放射性标记的 TAT 修饰的单克隆抗体对肿瘤组织中 p53 进行无创体内分子成像的可行性。