Extracellular matrix metalloproteinase inducer CD147 is a glycoprotein on the cell surface. There is minimal expression of CD147 in normal epithelial and fetal tissues, but it is highly expressed in a number of aggressive tumors. CD147 has been implicated in pan-cancer immunity and progression. With the development of CD147-targeting therapeutic strategy, accurate detection of CD147 expression in tumors and its changes during the therapy is necessary. In this study we constructed a novel radiotracer by labeling the anti-CD147 mAb with radionuclide ^124/125I (^124/125I-anti-CD147) for noninvasive detection of CD147 expression in pan-cancers, and characterized its physicochemical properties, affinity, metabolic characteristics, biodistribution and immunoPET imaging with ¹²⁴I-IgG and ¹⁸F-FDG as controls. By examining the expression of CD147 in cancer cell lines, we found high CD147 expression in colon cancer cells LS174T, FADU human pharyngeal squamous cancer cells and 22RV1 human prostate cancer cells, and low expression of CD147 in human pancreatic cancer cells ASPC1 and human gastric cancer cells BGC823. ^124/125I-anti-CD147 was prepared using N-bromine succinimide (NBS) as oxidant and purified by PD-10 column. Its radiochemical purity (RCP) was over 99% and maintained over 85% in saline or 5% human serum albumin (HSA) for more than 7 d; the RCP of ¹²⁵I-anti-CD147 in blood was over 90% at 3 h post injection (p.i.) in healthy mice. The K_d value of ¹²⁵I-anti-CD147 to CD147 protein was 6.344 nM, while that of ¹²⁵I-IgG was over 100 nM. ¹²⁵I-anti-CD147 showed much greater uptake in CD147 high-expression cancer cells compared to CD147 low-expression cancer cells. After intravenous injection in healthy mice, ¹²⁵I-anti-CD147 showed high initial uptake in blood pool and liver, the uptake was decreased with time. The biological half-life of distribution and clearance phases in healthy mice were 0.63 h and 19.60 h, respectively. The effective dose of ¹²⁴I-anti-CD147 was estimated as 0.104 mSv/MBq. We conducted immunoPET imaging in tumor-bearing mice, and demonstrated a significantly higher tumor-to-muscle ratio of ¹²⁴I-anti-CD147 compared to that of ¹²⁴I-IgG and ¹⁸F-FDG in CD147 (+) tumors. The expression levels of CD147 in cells and tumors were positively correlated with the maximum standardized uptake value (SUV_max) (P < 0.01). In conclusion, ^124/125I-anti-CD147 displays high affinity to CD147, and represents potential for the imaging of CD147-positive tumors. The development of ¹²⁴I-anti-CD147 may provide new insights into the regulation of tumor microenvironment and formulation of precision diagnosis and treatment programs for tumors.

细胞外基质金属蛋白酶诱导剂 CD147 是细胞表面的一种糖蛋白。 CD147 在正常上皮组织和胎儿组织中表达极少，但在许多侵袭性肿瘤中高表达。 CD147 与泛癌免疫和进展有关。随着CD147靶向治疗策略的发展，准确检测肿瘤中CD147的表达及其在治疗过程中的变化是必要的。在本研究中，我们通过用放射性核素^124/125 I ( ^124/125 I-anti-CD147) 标记抗 CD147 mAb 构建了一种新型放射性示踪剂，用于无创检测泛癌中 CD147 的表达，并表征了其理化性质、亲和力、以¹²⁴ I-IgG 和¹⁸ F-FDG 作为对照的代谢特征、生物分布和免疫 PET 成像。通过检测癌细胞系中CD147的表达，我们发现结肠癌细胞LS174T、FADU人咽鳞癌细胞和22RV1人前列腺癌细胞中CD147高表达，而人胰腺癌细胞ASPC1和人胃癌中CD147低表达。细胞BGC823。以N-溴琥珀酰亚胺(NBS)为氧化剂制备^124/125 I-抗CD147，并通过PD-10柱纯化。其放射化学纯度（RCP）在99%以上，在生理盐水或5%人血清白蛋白（HSA）中保持85%以上7d以上；健康小鼠注射后 3 小时 (pi) 时，血液中¹²⁵ I-抗 CD147 的 RCP 超过 90%。 ¹²⁵ I-抗CD147对CD147蛋白的Kd值为6.344nM，而^125I -IgG的_Kd值超过100nM。 与 CD147 低表达癌细胞相比， ¹²⁵ I-抗 CD147 在 CD147 高表达癌细胞中表现出更高的摄取。健康小鼠静脉注射¹²⁵ I-anti-CD147 后，血池和肝脏初始摄取量较高，随时间推移摄取量逐渐减少。健康小鼠分布期和清除期的生物半衰期分别为0.63小时和19.60小时。 ¹²⁴ I-抗CD147的有效剂量估计为0.104 mSv/MBq。我们对荷瘤小鼠进行了免疫 PET 成像，结果表明，在 CD147 (+) 肿瘤中， ¹²⁴ I-抗 CD147 的肿瘤与肌肉的比率显着高于¹²⁴ I-IgG 和¹⁸ F-FDG。细胞和肿瘤中CD147的表达水平与最大标准化摄取值（SUV _max ）呈正相关（ P < 0.01）。总之， ^124/125 I-抗CD147对CD147表现出高亲和力，并且代表了CD147阳性肿瘤成像的潜力。 ¹²⁴ I-anti-CD147的开发可能为肿瘤微环境的调控和肿瘤精准诊疗方案的制定提供新的见解。