Towards Effective Targeted Alpha Therapy for Neuroendocrine Tumours: A Review

Area of Science:

• Oncology
• Nuclear Medicine
• Radiopharmacology

Background:

• Molecular Radiotherapy (MRT) and Peptide Receptor Radionuclide Therapy (PRRT) are established treatments for neuroendocrine tumours (NETs).
• Current PRRT primarily utilizes beta-emitting radiopharmaceuticals targeting somatostatin subtype 2 receptors (SSTR2).
• Limitations exist with beta-emitting agents, prompting exploration of alternative therapies.

Purpose of the Study:

• To review the evolution of PRRT in NETs, focusing on the transition to alpha-emitting agents.
• To critically analyze the radiobiological basis, clinical applications, and developments in Targeted Alpha Therapy (TAT).
• To evaluate the potential of TAT in SSTR2-overexpressing cancers, particularly in patients resistant to beta-PRRT.

Main Methods:

• Extensive literature review of preclinical and clinical studies on PRRT and TAT.
• Analysis of radiobiological principles governing alpha and beta particle emissions.
• Evaluation of targeting mechanisms, efficacy, and toxicity profiles of different radiopharmaceuticals.

Main Results:

• PRRT effectively targets SSTR2-expressing NETs, but limitations necessitate improved therapies.
• Targeted Alpha Therapy (TAT) offers higher potency and specificity due to alpha-particle emissions.
• TAT demonstrates potential for enhanced therapeutic efficacy and reduced toxicity compared to beta-emitters.

Conclusions:

• TAT holds significant promise for treating SSTR2-overexpressing cancers, especially in patients refractory to beta-PRRT.
• Standardized dosimetry and a deeper understanding of dose-response relationships are crucial for TAT optimization.
• Further research is essential to refine TAT protocols and overcome current challenges for widespread clinical application.