首例人体研究：使用（68）Ga-NODAGA-THERANOST（一种靶向αvβ3整合素受体的高亲和力拟肽）通过PET/CT成像证明肿瘤血管生成。
First-In-Human Study Demonstrating Tumor-Angiogenesis by PET/CT Imaging with (68)Ga-NODAGA-THERANOST, a High-Affinity Peptidomimetic for αvβ3 Integrin Receptor Targeting.
作者信息
Baum Richard P, Kulkarni Harshad R, Müller Dirk, Satz Stanley, Danthi Narasimhan, Kim Young-Seung, Brechbiel Martin W
机构信息
1 THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, ENETS Center of Excellence , Bad Berka, Germany .
出版信息
Cancer Biother Radiopharm. 2015 May;30(4):152-9. doi: 10.1089/cbr.2014.1747.
UNLABELLED
(68)Ga-NODAGA-THERANOST™ is an αvβ3 integrin antagonist and the first radiolabeled peptidomimetic to reach clinical development for targeting integrin receptors. In this first-in-human study, the feasibility of integrin receptor peptidomimetic positron emission tomography/computed tomography (PET/CT) imaging was confirmed in patients with non-small-cell lung cancer and breast cancer.
METHODS
Patients underwent PET/CT imaging with (68)Ga NODAGA-THERANOST. PET images were analyzed qualitatively and quantitatively and compared to 2-deoxy-2-((18)F) fluoro-d-glucose ((18)F-FDG) findings. Images were obtained 60 minutes postinjection of 300-500 MBq of (68)Ga-NODAGA-THERANOST.
RESULTS
(68)Ga-NODAGA-THERANOST revealed high tumor-to-background ratios (SUVmax=4.8) and uptake at neoangiogenesis sites. Reconstructed fused images distinguished cancers with high malignancy potential and enabled enhanced bone metastasis detection. (18)F-FDG-positive lung and lymph node metastases did not show uptake, indicating the absence of neovascularization.
CONCLUSIONS
(68)Ga-NODAGA-THERANOST was found to be safe and effective, exhibiting in this study rapid blood clearance, stability, rapid renal excretion, favorable biodistribution and PK/PD, low irradiation burden (μSv/MBq/μg), and convenient radiolabeling. This radioligand might enable theranostics, that is, a combination of diagnostics followed by the appropriate therapeutics, namely antiangiogenic therapy, image-guided presurgical assessment, treatment response evaluation, prediction of pathologic response, neoadjuvant-peptidomimetic-radiochemotherapy, and personalized medicine strategies. Further clinical trials evaluating (68)Ga-NODAGA-THERANOST are warranted.
未标记
（68）Ga-NODAGA-THERANOST™是一种αvβ3整合素拮抗剂，也是首个进入临床开发阶段用于靶向整合素受体的放射性标记拟肽。在这项首次人体研究中，非小细胞肺癌和乳腺癌患者中整合素受体拟肽正电子发射断层扫描/计算机断层扫描（PET/CT）成像的可行性得到了证实。
方法
患者接受（68）Ga NODAGA-THERANOST的PET/CT成像。对PET图像进行定性和定量分析，并与2-脱氧-2-（（18）F）氟-D-葡萄糖（（18）F-FDG）检查结果进行比较。在注射300-500 MBq的（68）Ga-NODAGA-THERANOST后60分钟获得图像。
结果
（68）Ga-NODAGA-THERANOST显示出高肿瘤与背景比值（SUVmax=4.8）以及在新生血管生成部位的摄取。重建的融合图像能够区分具有高恶性潜能的癌症，并能增强骨转移的检测。（18）F-FDG阳性的肺和淋巴结转移灶未显示摄取，表明不存在新生血管形成。
结论
发现（68）Ga-NODAGA-THERANOST安全有效，在本研究中表现出快速的血液清除、稳定性、快速的肾脏排泄、良好的生物分布和药代动力学/药效学、低辐射负担（μSv/MBq/μg）以及便捷的放射性标记。这种放射性配体可能实现诊疗一体化，即诊断与适当治疗（即抗血管生成治疗）相结合，进行图像引导的术前评估、治疗反应评估、病理反应预测、新辅助拟肽放化疗以及个性化医疗策略。有必要进一步开展评估（68）Ga-NODAGA-THERANOST的临床试验。
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