Objective To evaluate the radiation dosimetry, pharmacokinetics, and safety of ¹⁷⁷Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotate (¹⁷⁷Lu-DOTA-TATE) in the treatment of advanced metastatic neuroendocrine tumors (NETs).

Methods A prospective analysis was performed for 6 patients with advanced metastatic NETs diagnosed by histopathological examination in the First Medical Center of PLA General Hospital from July 2021 to March 2022, including 4 males and 2 females, aged (50.2±9.6) years old. Patients were given intravenous injection of ¹⁷⁷Lu-DOTA-TATE at a single dose of (7 400±740) MBq for up to 4 cycles, with each cycle interval of (8±1) weeks. Considering the difficulties in the supply of ¹⁷⁷LuCl₃ raw materials owing to pandemic, only 3 patients received a full 4 cycles of treatment, 1 patient received 3 cycles treatment and 2 patients received 1 cycles treatment and then withdrew from the study. The distribution and metabolism of ¹⁷⁷Lu-DOTA-TATE in patients were analyzed, and the related parameters such as radiation dosimetry and pharmacokinetics were calculated, safety follow-up was also carried out. Patients undergoing radiation dosimetry and pharmacokinetic studies were subjected to SPECT images, blood samples, and urine samples at different time points after the first dose. Paired-sample t-test was used to compare the measured data with normal distribution and homogeneity of variance.

Results The dosimetry study of ¹⁷⁷Lu-DOTA-TATE was completed in 3 patients with NETs. The absorbed dose of ¹⁷⁷Lu-DOTA-TATE decreased in the following order: focus > kidney > spleen > liver. Three patients completed the pharmacokinetics study at the same time; the average calculated peak concentration (C_max) was 16.61 μg/L, and the average concentration time AUC (AUC_0-t) from zero to the last quantifiable concentration was 57.11 μg/(L·h). The average value of AUC (AUC_0-∞) extrapolated from zero to infinity was 76.25 μg/(L·h), the average apparent volume of distribution (V_z) was 222.55 L, the average clearance rate (CL) was 3.44 L/h, and the average half-life (T_1/2α) of the distributed phase was 0.89 h. The mean half-life (T_1/2β) of the elimination phase was 48.94 h. ¹⁷⁷Lu-DOTA-TATE was metabolized primarily by the kidney. The cumulative excretion rate of ¹⁷⁷Lu-DOTA-TATE was 61.05% within 48 h after administration. No serious adverse events occurred during the safety follow-up period after ¹⁷⁷Lu-DOTA-TATE therapy in 6 patients. No significant difference in blood routine, blood biochemistry, coagulation function and urine routine was found before and after treatment (t=−1.437 to 1.378, all P>0.05).

Conclusions ¹⁷⁷Lu-DOTA-TATE is excreted mostly in the urinary system, with rapid clearance in vivo and high tumor uptake. It has good safety and tolerance in patients with advanced metastatic neuroendocrine tumors.