Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research "Demokritos", Aghia Paraskevi, 153 10, Athens, Greece.
Department of Molecular Biotechnology and Health Sciences, University of Turin, via Nizza 52, Torino, Italy.
Mol Imaging Biol. 2018 Oct;20(5):798-807. doi: 10.1007/s11307-018-1176-0.
The aim of this study was to demonstrate the potential of Ga-68-labeled macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor recognition by positron emission tomography (PET), based on targeting of the overexpressed sialic acid (Sia).
The imaging reporter DOTA-en-pba was synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel-C and B16-F10 melanoma cells was used to evaluate melanin production and Sia overexpression to determine the best model for demonstrating the capability of [Ga]DOTA-en-pba to recognize tumors. The in vivo PET imaging was done with B16-F10 tumor-bearing SCID mice injected with [Ga]DOTA-en-pba intravenously. Tumor, blood, and urine metabolites were assessed to evaluate the presence of a targeting agent.
The affinity of [Ga]DOTA-en-pba to Sia was demonstrated on B16-F10 melanoma cells, after the production of melanin as well as Sia overexpression was proved to be up to four times higher in this cell line compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing SCID mice showed blood clearance at the time points studied, while uptake in the tumor peaked at 60 min post-injection (6.36 ± 2.41 % ID/g). The acquired PET images were in accordance with the ex vivo biodistribution results. Metabolite assessment on tumor, blood, and urine samples showed that [Ga]DOTA-en-pba remains unmetabolized up to at least 60 min post-injection.
Our work is the first attempt for in vivo imaging of cancer by targeting overexpression of sialic acid on cancer cells with a radiotracer in PET.
本研究旨在展示基于靶向过度表达的唾液酸（Sia），使用 Ga-68 标记的大环（DOTA-en-pba）与苯硼酸载体结合物进行正电子发射断层扫描（PET）肿瘤识别的潜力。
合成了成像报告分子 DOTA-en-pba，并以高效率进行 Ga-68 标记。在黑色素瘤 Mel-C 和 B16-F10 细胞上进行细胞结合实验，评估黑色素生成和 Sia 过度表达，以确定最佳模型来证明[Ga]DOTA-en-pba 识别肿瘤的能力。通过静脉内注射[Ga]DOTA-en-pba 对 B16-F10 肿瘤荷瘤 SCID 小鼠进行体内 PET 成像。评估肿瘤、血液和尿液代谢产物，以评估靶向剂的存在。
在 B16-F10 黑色素瘤细胞上证明了[Ga]DOTA-en-pba 与 Sia 的亲和力，在该细胞系中，黑色素生成以及 Sia 过度表达被证明比 Mel-C 细胞高四倍。在 B16-F10 肿瘤荷瘤 SCID 小鼠中的生物分布研究显示，在研究的时间点上血液清除率高，而在注射后 60 分钟时肿瘤摄取达到峰值（6.36±2.41% ID/g）。获得的 PET 图像与体外生物分布结果一致。对肿瘤、血液和尿液样本的代谢产物评估表明，[Ga]DOTA-en-pba 在至少 60 分钟的注射后仍未代谢。
我们的工作首次尝试使用放射性示踪剂通过靶向癌细胞上过度表达的唾液酸在 PET 中对癌症进行体内成像。
