TY - JOUR
T1 - Towards Effective Targeted Alpha Therapy for Neuroendocrine Tumours
T2 - A Review
AU - Gape, Paul M.D.
AU - Schultz, Michael K.
AU - Stasiuk, Graeme J.
AU - Terry, Samantha Y.A.
N1 - Funding Information:
This work was partially supported by the EPSRC Centre for Doctoral Training in Smart Medical Imaging [EP/S022104/1] and Perspective Therapeutics (PG). S.Y.A.T. was supported by MRC Grant [MR/X00841X/1]. G.J.S. would like to thank the MRC [MR/T002573/1] and EPSRC [EP/V027549/1 and EP/T026367/1] for funding. M.K.S. was supported by grants R44CA268314, R44CA250872, R44CA254613, 1R01CA243014, 1P50CA174521 from the NIH/NCI, and is an employee of Perspective Therapeutics.
Publisher Copyright:
© 2024 by the authors.
PY - 2024/3
Y1 - 2024/3
N2 - This review article explores the evolving landscape of Molecular Radiotherapy (MRT), emphasizing Peptide Receptor Radionuclide Therapy (PRRT) for neuroendocrine tumours (NETs). The primary focus is on the transition from β-emitting radiopharmaceuticals to α-emitting agents in PRRT, offering a critical analysis of the radiobiological basis, clinical applications, and ongoing developments in Targeted Alpha Therapy (TAT). Through an extensive literature review, the article delves into the mechanisms and effectiveness of PRRT in targeting somatostatin subtype 2 receptors, highlighting both its successes and limitations. The discussion extends to the emerging paradigm of TAT, underlining its higher potency and specificity with α-particle emissions, which promise enhanced therapeutic efficacy and reduced toxicity. The review critically evaluates preclinical and clinical data, emphasizing the need for standardised dosimetry and a deeper understanding of the dose-response relationship in TAT. The review concludes by underscoring the significant potential of TAT in treating SSTR2-overexpressing cancers, especially in patients refractory to β-PRRT, while also acknowledging the current challenges and the necessity for further research to optimize treatment protocols.
AB - This review article explores the evolving landscape of Molecular Radiotherapy (MRT), emphasizing Peptide Receptor Radionuclide Therapy (PRRT) for neuroendocrine tumours (NETs). The primary focus is on the transition from β-emitting radiopharmaceuticals to α-emitting agents in PRRT, offering a critical analysis of the radiobiological basis, clinical applications, and ongoing developments in Targeted Alpha Therapy (TAT). Through an extensive literature review, the article delves into the mechanisms and effectiveness of PRRT in targeting somatostatin subtype 2 receptors, highlighting both its successes and limitations. The discussion extends to the emerging paradigm of TAT, underlining its higher potency and specificity with α-particle emissions, which promise enhanced therapeutic efficacy and reduced toxicity. The review critically evaluates preclinical and clinical data, emphasizing the need for standardised dosimetry and a deeper understanding of the dose-response relationship in TAT. The review concludes by underscoring the significant potential of TAT in treating SSTR2-overexpressing cancers, especially in patients refractory to β-PRRT, while also acknowledging the current challenges and the necessity for further research to optimize treatment protocols.
KW - molecular radiotherapy
KW - neuroendocrine tumours
KW - peptide receptor radionuclide therapy
KW - targeted alpha therapy
KW - targeted radionuclide therapy
UR - http://www.scopus.com/inward/record.url?scp=85189009226&partnerID=8YFLogxK
U2 - 10.3390/ph17030334
DO - 10.3390/ph17030334
M3 - Review article
AN - SCOPUS:85189009226
SN - 1424-8247
VL - 17
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 3
M1 - 334
ER -
