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

Objective: (177)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 (177)Lu-DOTA-EB-TATE in patients with advanced neuroendocrine neoplasm (NEN). Methods: With IRB approval and informed consent, 4 NEN patients were enrolled to undergo (177)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 (177)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 (68)Ga-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. Results: All 4 patients subjected to (177)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(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 (r = -0.852, P < 0.001). Compared with the control (177)Lu-DOTA-TATE therapy, the (177)Lu-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 SUV(max) from 10.0-35.0. Conclusion: A single low-dose (177)Lu-DOTA-EB-TATE treatment appears to be safe and effective in the treatment of NENs with high (68)Ga-DOTA-TATE uptake. This pilot study merits further investigation with increased dose and frequency of (177)Lu-DOTA-EB-TATE administration with potential advantages over (177)Lu-DOTA-TATE.