Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Gynecological Oncology, Henan Provincial Tumor Hospital, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Clin Cancer Res. 2020 Mar 15;26(6):1318-1326. doi: 10.1158/1078-0432.CCR-19-1845. Epub 2019 Dec 16.
Tumor periphery and lymph nodes of tumor-induced lymphangiogenesis often abundantly express VEGFR-3. In our previous study, we identified a 5-amino acid peptide named TMVP1, which binds specifically to VEGFR-3. The objective of this study was to develop a novel Ga-labeled TMVP1 for VEGFR-3 PET imaging and to investigate its safety, biodistribution, and tumor-localizing efficacy in xenograft tumor models and a small cohort of patients with recurrent ovarian and cervical cancer.
The DOTA-conjugated TMVP1 peptide was labeled with radionuclide Ga. SPR and saturation binding assays were used for the receptor-binding studies. Gynecologic xenograft tumors were employed for small-animal PET imaging and biodistribution of Ga-DOTA-TMVP1 . In the clinical study, 5 healthy volunteers and 8 patients with gynecologic cancer underwent whole-body PET/CT after being injected with Ga-DOTA-TMVP1.
DOTA-TMVP1 was successfully labeled with Ga. LECs showed higher binding capacity with Ga-DOTA-TMVP1 than LEC(shVEGFR-3) and human umbilical vein endothelial cells. In mice with subcutaneous C33-A and SKOV-3 xenografts, the tracer was rapidly eliminated through the kidney to the bladder, and the small-animal PET/CT helped to clearly visualize the tumors. In patients with recurrent ovarian cancer and cervical cancer, tracer accumulation well above the background level was demonstrated in most identified sites of disease; especially with recurrent endodermal sinus tumors, the diagnostic value of Ga-DOTA-TMVP1 was comparable with that of F-FDG PET/CT.
Ga-DOTA-TMVP1 is a potential PET tracer for imaging VEGFR-3 with favorable pharmacokinetics.
肿瘤诱导的淋巴管生成的肿瘤周围和淋巴结常常丰富地表达 VEGFR-3。在我们之前的研究中，我们鉴定了一种名为 TMVP1 的 5 个氨基酸肽，它能特异性地与 VEGFR-3 结合。本研究的目的是开发一种新的 Ga 标记的 TMVP1，用于 VEGFR-3 PET 成像，并在异种移植肿瘤模型和一小部分复发性卵巢和宫颈癌患者中研究其安全性、生物分布和肿瘤定位效果。
DOTA 偶联的 TMVP1 肽被放射性核素 Ga 标记。表面等离子体共振（SPR）和饱和结合测定用于受体结合研究。妇科异种移植肿瘤用于 Ga-DOTA-TMVP1 的小动物 PET 成像和生物分布。在临床研究中，5 名健康志愿者和 8 名妇科癌症患者在注射 Ga-DOTA-TMVP1 后接受全身 PET/CT 检查。
DOTA-TMVP1 成功地与 Ga 标记。LEC 与 Ga-DOTA-TMVP1 的结合能力高于 LEC（shVEGFR-3）和人脐静脉内皮细胞。在皮下 C33-A 和 SKOV-3 异种移植瘤小鼠中，示踪剂迅速通过肾脏排泄到膀胱，小动物 PET/CT 有助于清晰地显示肿瘤。在复发性卵巢癌和宫颈癌患者中，在大多数确定的疾病部位显示出高于背景水平的示踪剂积累；特别是对于复发性内胚窦瘤，Ga-DOTA-TMVP1 的诊断价值与 F-FDG PET/CT 相当。
Ga-DOTA-TMVP1 是一种潜在的用于 VEGFR-3 成像的 PET 示踪剂，具有良好的药代动力学特性。
