Targeted alpha-particle therapy in neuroendocrine neoplasms: A systematic review

Area of Science:

• Oncology
• Nuclear Medicine
• Radiopharmaceutical Therapy

Background:

• Neuroendocrine neoplasms (NENs) are increasingly diagnosed worldwide, with systemic therapy crucial for unresectable or metastatic cases.
• ¹⁷⁷Lu-DOTATATE is a beta-particle emitting radiopharmaceutical effective for metastatic gastroenteropancreatic NENs (GEP-NENs).
• Limited treatment options exist following ¹⁷⁷Lu-DOTATATE therapy failure, necessitating exploration of novel approaches.

Purpose of the Study:

• To review existing evidence on targeted alpha-particle therapy (TAT) for metastatic NENs, focusing on GEP-NENs.
• To identify potential adverse events associated with TAT in this patient population.
• To summarize the efficacy and safety of alpha-particle emitting radiopharmaceuticals for advanced NENs.

Main Methods:

• A systematic literature search was conducted across MEDLINE, EMBASE, SCOPUS, and Cochrane Library databases.
• Inclusion criteria were applied to identify relevant studies on TAT for metastatic NENs.
• Two articles meeting the criteria were included in this review.

Main Results:

• ²²⁵Actinium (²²⁵Ac)-DOTATATE and ²¹³Bismuth (²¹³Bi)-DOTATOC are potential TAT agents for metastatic NENs.
• Evidence suggests partial responses were achieved with both agents.
• No significant hematological, renal, or hepatotoxicity was reported.

Conclusions:

• TAT, particularly ²²⁵Ac-DOTATATE, represents a promising therapeutic avenue for metastatic NENs, especially after ¹⁷⁷Lu-DOTATATE failure.
• Current evidence indicates a favorable safety profile regarding key organ systems.
• Further research, including long-term randomized controlled trials, is warranted to establish the definitive role of TAT in NEN management.