Response to Single Low-dose (177)Lu-DOTA-EB-TATE Treatment in Patients with Advanced Neuroendocrine Neoplasm: A Prospective Pilot Study.
Response to Single Low-dose (177)Lu-DOTA-EB-TATE Treatment in Patients with Advanced Neuroendocrine Neoplasm: A Prospective Pilot Study.
复制标题
晚期神经内分泌肿瘤患者对单次低剂量 Lu-177-DOTA-EB-TATE 治疗的反应：一项前瞻性试点研究
作者：
Wang H;Cheng Y;Zhang J;Zang J;Li H;Liu Q;Wang J;Jacobson O;Li F;Zhu Z;Chen X
目的：177Lu-DOTA-EB-Tate是一种以八氢叶酸为基础的药物，它利用伊文思蓝结构与白蛋白结合，改善药物动力学和药效学。这项先导性研究旨在评估单次小剂量使用177Lu-DOTA-EB-Tate治疗晚期神经内分泌肿瘤(NEN)的疗效。方法：在获得IRB批准和知情同意的情况下，4例NEN患者接受177Lu-DOTA-EB-Tate治疗，单次小剂量剂量为0.66±0.06GBq(17.8±1.7mCi)，3例NEN患者接受177Lu-DOTA-Tate治疗，治疗活度为3.98±0.17GBq(107.6±4.6MCI)。对7例患者的1个原发灶和62个转移灶在治疗前即刻、治疗后1~3个月行68Ga-DOTA-Tate PET/CT检查。测量肿瘤直径≥2.0 cm的最大SUV(SUVmax)，计算治疗后ΔSUV值的变化百分率。结果：接受177Lu-DOTA-EB-Tate治疗的4例患者均耐受，无明显不良反应，症状缓解。40个肿瘤≥直径2.0 cm，治疗前、后3个月Δ最大血流速度为-75.1%~2 6.3%(-38.9±2 5.5%)。2 9例(72.5%)肿瘤的SUVmax下降15%(Δ为-75.1%-17.1%)。基线最大血流速度与治疗后Δ最大血流速度呈显著负相关(r=-0.852，P<0.001)。与177Lu-DOTA-Tate对照组相比，剂量约为1/6的177 Lu-DOTA-EB-Tate治疗组的ΔSUV值无显著差异(-7.9±5.4%比-5.8±3.9%，P=0.189)。结论：单次小剂量177Lu-DOTA-EB-Tate治疗高摄取68Ga-DOTA-Tate的NES是安全有效的。这项先导性研究值得进一步研究，增加剂量和频率的177Lu-DOTA-EB-Tate给药，其潜在优势是177Lu-DOTA-Tate。
Objective: 177Lu-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 177Lu-DOTA-EB-TATE in patients with advanced neuroendocrine neoplasm (NEN). Methods: With IRB approval and informed consent, 4 NEN patients were enrolled to undergo 177Lu-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 177Lu-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 68Ga-DOTA-TATE PET/CT immediately before and one or three months after the treatment. Maximum SUV (SUVmax) of the tumors ≥2.0 cm in diameter were measured and percentage of change (ΔSUV) after treatment were calculated. Results: All 4 patients subjected to 177Lu-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 SUVmax 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 SUVmax (ΔSUV = -75.1%--17.1%). There was a significant negative correlation between the baseline SUVmax and the ΔSUV after treatment (r = -0.852, P < 0.001). Compared with the control 177Lu-DOTA-TATE therapy, the 177Lu-DOTA-EB-TATE treatment using approximately 1/6 the dose showed no significant difference in ΔSUV (-7.9 ± 5.4% vs. -5.8 ± 3.9%, P = 0.189) as demonstrated by the tumors with comparable baseline SUVmax from 10.0-35.0. Conclusion: A single low-dose 177Lu-DOTA-EB-TATE treatment appears to be safe and effective in the treatment of NENs with high 68Ga-DOTA-TATE uptake. This pilot study merits further investigation with increased dose and frequency of 177Lu-DOTA-EB-TATE administration with potential advantages over 177Lu-DOTA-TATE.