Response to Single Low-dose ¹⁷⁷Lu-DOTA-EB-TATE Treatment in Patients with Advanced Neuroendocrine Neoplasm: A Prospective Pilot Study

Abstract

<b>Objective:</b>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). <b>Methods:</b> 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 (SUV_max) of the tumors ≥2.0 cm in diameter were measured and percentage of change (ΔSUV) after treatment were calculated. <b>Results:</b> 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 SUV_max 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_max (ΔSUV = -75.1%--17.1%). There was a significant negative correlation between the baseline SUV_max and the ΔSUV after treatment (<i>r</i> = -0.852, <i>P</i> < 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% <i>vs.</i> -5.8 ± 3.9%, <i>P</i> = 0.189) as demonstrated by the tumors with comparable baseline SUV_max from 10.0-35.0. <b>Conclusion</b>: 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.