Department of Nuclear Medicine, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Science and PUMC, Beijing 100730, China.
Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Science and PUMC, Beijing 100730, China.
Theranostics. 2018 May 12;8(12):3308-3316. doi: 10.7150/thno.25919. eCollection 2018.
Lu-DOTA-EB-TATE is a theranostic agent based on octreotate that uses an Evans blue structure to bind albumin to improve the pharmacokinetics and pharmacodynamics. This pilot study aims to evaluate the efficacy of a single low-dose treatment using Lu-DOTA-EB-TATE in patients with advanced neuroendocrine neoplasm (NEN). With IRB approval and informed consent, 4 NEN patients were enrolled to undergo Lu-DOTA-EB-TATE treatment with a single low dose of 0.66 ± 0.06 GBq (17.8 ± 1.7 mCi); 3 other NEN patients were enrolled as controls to undergo Lu-DOTA-TATE treatment with administered activity of 3.98 ± 0.17 GBq (107.6 ± 4.6 mCi). One primary tumor and 62 metastatic lesions in the 7 patients were evaluated by Ga-DOTA-TATE PET/CT immediately before and one or three months after the treatment. Maximum SUV (SUV) of the tumors ≥2.0 cm in diameter were measured and percentage of change (ΔSUV) after treatment were calculated. All 4 patients subjected to Lu-DOTA-EB-TATE treatment tolerated the administered activity without significant adverse effects and showed symptomatic remission. Among the patients, 40 tumors were found with diameter ≥2.0 cm, with the baseline SUV varied from 1.5-82.9 (35.9 ± 21.0) and the ΔSUVs before and three months after the treatment from -75.1-26.3% (-38.9 ± 25.5%). Twenty-nine (72.5%) of the tumors showed >15% decrease of SUV (ΔSUV = -75.1%--17.1%). There was a significant negative correlation between the baseline SUV and the ΔSUV after treatment ( = -0.852, < 0.001). Compared with the control Lu-DOTA-TATE therapy, the Lu-DOTA-EB-TATE treatment using approximately 1/6 the dose showed no significant difference in ΔSUV (-7.9 ± 5.4% -5.8 ± 3.9%, = 0.189) as demonstrated by the tumors with comparable baseline SUV from 10.0-35.0. : A single low-dose Lu-DOTA-EB-TATE treatment appears to be safe and effective in the treatment of NENs with high Ga-DOTA-TATE uptake. This pilot study merits further investigation with increased dose and frequency of Lu-DOTA-EB-TATE administration with potential advantages over Lu-DOTA-TATE.
Lu-DOTA-EB-TATE 是一种基于奥曲肽的治疗药物，它使用 Evans 蓝结构来结合白蛋白，以改善药代动力学和药效学。这项初步研究旨在评估单低剂量 Lu-DOTA-EB-TATE 治疗晚期神经内分泌肿瘤 (NEN) 患者的疗效。经机构审查委员会批准和知情同意，4 名 NEN 患者接受了 Lu-DOTA-EB-TATE 治疗，剂量为 0.66 ± 0.06GBq（17.8 ± 1.7mCi）；另外 3 名 NEN 患者作为对照组，接受了 Lu-DOTA-TATE 治疗，给予的活性为 3.98 ± 0.17GBq（107.6 ± 4.6mCi）。7 名患者的 1 个原发肿瘤和 62 个转移病灶在治疗前和治疗后 1 或 3 个月，用 Ga-DOTA-TATE PET/CT 进行了评估。测量了直径≥2.0cm 的肿瘤的最大 SUV（SUV），并计算了治疗后的 SUV 变化率（ΔSUV）。接受 Lu-DOTA-EB-TATE 治疗的 4 名患者均耐受了给予的活性，无明显不良反应，并出现症状缓解。在患者中，发现 40 个肿瘤直径≥2.0cm，基线 SUV 值为 1.5-82.9（35.9 ± 21.0），治疗前后 3 个月 SUV 值为-75.1%-26.3%（-38.9 ± 25.5%）。29 个（72.5%）肿瘤 SUV 下降超过 15%（ΔSUV=-75.1%-17.1%）。基线 SUV 与治疗后 SUV 变化率呈显著负相关（ = -0.852， < 0.001）。与对照组 Lu-DOTA-TATE 治疗相比，使用约 1/6 剂量的 Lu-DOTA-EB-TATE 治疗在具有可比性的基线 SUV（10.0-35.0）的肿瘤中，ΔSUV 无显著差异（-7.9 ± 5.4%-5.8 ± 3.9%， = 0.189）。：单低剂量 Lu-DOTA-EB-TATE 治疗似乎对高 Ga-DOTA-TATE 摄取的 NEN 是安全有效的。这项初步研究值得进一步研究，增加 Lu-DOTA-EB-TATE 的剂量和给药频率，可能优于 Lu-DOTA-TATE。
