Initial Findings on the Use of [225Ac]Ac-DOTATATE Therapy as a Theranostic Application in Patients with Neuroendocrine Tumors.

Objectives: This study aimed to evaluate the stability, safety, and efficacy of alpha-targeted therapy with [²²⁵Ac]Ac-DOTATATE in patients with grade 1/2 metastatic neuroendocrine tumors (NETs).

Methods: This retrospective cohort included patients (n=11) with metastatic NETs from different primary sites (bronchial, pancreatic, nonpancreatic gastroenteropancreatic NETs, paraganglioma, and unknown primary site) treated with [²²⁵Ac]Ac-DOTATATE with a mean activity of 8.2±0.6 MBq (range: 7.5-10.0 MBq) at our institution between November 2019 and March 2022. The in vivo and in vitro stability of [²²⁵Ac]Ac-DOTATATE was calculated. The safety profile was evaluated according to the CTCAE-v5.0. Treatment efficacy was evaluated according to [⁶⁸Ga] Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) images and the RECIST 1.1 criteria.

Results: Patients had 73% (n=8) lymph node metastases, 91% (n=10) liver metastases, 36% (n=4) lung metastases, and 73% (n=8) bone metastases. All but one patient was refractory to treatment with [¹⁷⁷Lu]Lu-DOTATATE. [²²⁵Ac]Ac-DOTATATE was stable for at least 5 h in vitro (in saline) and 3 h in vivo (urine and blood samples). Grade 2 renal toxicity and grade 2 hematotoxicity were observed in one patient. No grade 3-4 toxicities were reported. According to post-treatment [⁶⁸Ga]Ga-DOTATATE PET/CT (n=9), 11% (n=1) had progressive disease, 44.4% (n=4) had stable disease, and 44.4% (n=4) had a partial response. The disease control rate was 89% (n=8). The median progression-free survival estimated according to Kaplan-Meier analysis was 12 months.

Conclusion: The preliminary results of this study suggest that [²²⁵Ac]Ac-DOTATATE is stable, safe, and effective for treating advanced and [¹⁷⁷Lu] Lu-DOTATATE-refractory NETs. However, prospective studies are needed to determine the impact of treatment on overall survival and to uncover potential side effects.