Xu Wei, Yan Junjie, Zhong Xinlin, Pan Donghui, Wang Xinyu, Xu Yuping, Wang Lizhen, Chen Chongyang, Yang Min
School of Life Sciences and Health Engineering, Jiangnan University, Jiangsu, 214122, China.
School of Chemical and Material Engineering, Jiangnan University, Jiangsu, 214122, China.
EJNMMI Radiopharm Chem. 2025 Jul 22;10(1):46. doi: 10.1186/s41181-025-00373-4.
Poly(ADP-ribose) polymerase (PARP) is an important therapeutic target in cancer treatment, and dynamic assessment of its expression level is essential for achieving precision therapy. Although F-labeled PARP-targeted radiotracers have demonstrated remarkable tumor-imaging capabilities in preclinical studies, their high lipophilicity leads to increased non-specific uptake in abdominal organs, which has severely hindered their clinical translation. Furthermore, while PET imaging provides superior resolution and sensitivity, its infrastructure and operational demands may limit widespread accessibility in certain regions. Therefore, the development of SPECT-based PARP radiotracers could offer a complementary approach, potentially expanding access to PARP imaging in a broader range of clinical settings. To provide a more affordable and accessible alternative to PET probes, hydrazinonicotinamide (HYNIC)-olaparib was radiolabeled with technetium-99m (Tc) and evaluated both in vitro and in vivo using the MDA-MB-453 breast cancer model.
[Tc][Tc-HYNIC/EDDA]-olaparib exhibits a high radiochemical yield (> 90%), excellent radiochemical purity (> 90%), and good in vitro stability. The introduction of ethylenediamine-N, N'-diacetic acid (EDDA) and tricine facilitated the synthesis of Tc complex, and improved the hydrophilicity (logP = 0.63 ± 0.25) of the probe as well, resulting in reduced the accumulation of radiation in the abdomen. In vitro results indicated that [Tc][Tc-HYNIC/EDDA]-olaparib could target PRAP-1 in MDA-MB-453 cells. In vivo experiments, micro SPECT/CT imaging provided clear visualization of MDA-MB-453 tumors with significant tumor-to-background distinction, and accumulation of [Tc][Tc-HYNIC/EDDA]-olaparib was quantified at 3.45 ± 0.17%ID/g at 1 h post intravenous injection.
These findings suggest that [Tc][Tc-HYNIC/EDDA]-olaparib holds great promise as a novel radiotracer for PARP imaging.
聚（ADP - 核糖）聚合酶（PARP）是癌症治疗中的一个重要治疗靶点，动态评估其表达水平对于实现精准治疗至关重要。尽管F标记的PARP靶向放射性示踪剂在临床前研究中已显示出卓越的肿瘤成像能力，但其高亲脂性导致腹部器官中非特异性摄取增加，这严重阻碍了它们的临床转化。此外，虽然PET成像提供了卓越的分辨率和灵敏度，但其基础设施和操作要求可能会限制某些地区的广泛可及性。因此，基于SPECT的PARP放射性示踪剂的开发可以提供一种补充方法，有可能在更广泛的临床环境中扩大PARP成像的可及性。为了提供一种比PET探针更经济实惠且易于获得的替代方案，用99m锝（Tc）对肼基烟酰胺（HYNIC）-奥拉帕利进行放射性标记，并使用MDA - MB - 453乳腺癌模型进行体外和体内评估。
[Tc][Tc - HYNIC/EDDA]-奥拉帕利表现出高放射化学产率（>90%）、优异的放射化学纯度（>90%）和良好的体外稳定性。乙二胺 - N，N'-二乙酸（EDDA）和三（羟甲基）甲基甘氨酸的引入促进了Tc配合物的合成，并且也提高了探针的亲水性（logP = 0.63±0.25），从而减少了腹部的辐射积累。体外结果表明，[Tc][Tc - HYNIC/EDDA]-奥拉帕利可以靶向MDA - MB - 453细胞中的PRAP - 1。在体内实验中，微型SPECT/CT成像清晰地显示了MDA - MB - 453肿瘤，肿瘤与背景有明显区分，静脉注射后1小时，[Tc][Tc - HYNIC/EDDA]-奥拉帕利的摄取量经定量为3.45±0.17%ID/g。
这些发现表明，[Tc][Tc - HYNIC/EDDA]-奥拉帕利作为一种用于PARP成像的新型放射性示踪剂具有很大的潜力。
