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

Objective: Lu-177-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-177-DOTA-EB-TATE in patients with advanced neuroendocrine neoplasm (NEN). Methods: With IRB approval and informed consent, 4 NEN patients were enrolled to undergo Lu-177-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-177-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-68-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 (Delta SUV) after treatment were calculated. Results: All 4 patients subjected to Lu-177-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 Delta SUVs before and three months after the treatment from -75.1-26.3% (-38.9 +/- 25.5%). Thirty-two (80.0%) of the tumors showed >15% decrease of SUVma. (Delta SUV = -75.1%- -17.1%). There was a significant negative correlation between the baseline SUVmax and the SUV after treatment (r = -0.852, P < 0.001). Compared with the control Lu-177-DOTA-TATE therapy, the Lu-177-DOTA-EB-TATE treatment using approximately 1/6 the dose showed no significant difference in Delta SUV (-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 Lu-177-DOTA-EB-TATE treatment appears to be safe and effective in the treatment of NENs with high Ga-68-DOTA-TATE uptake. This pilot study merits further investigation with increased dose and frequency of Lu-177-DOTA-EB-TATE administration with potential advantages over Lu-177-DOTA-TATE.