The evolution of PRRT for the treatment of neuroendocrine tumors; What comes next?
- PMID: 36387893
- PMCID: PMC9659917
- DOI: 10.3389/fendo.2022.941832
The evolution of PRRT for the treatment of neuroendocrine tumors; What comes next?
Abstract
Lu-177 has been developed for the treatment of patients with peptide receptor radionuclide therapy (PRRT). A second generation pure no-carrier-added Lu-177 has a high specific activity and has waste disposal advantages over the first generation carrier-added Lu-177. PRRT has recently been developed for the treatment of neuroendocrine tumors (NETs). The majority of pancreatic and gastroenteric NETs (GEP-NETs) express the somatostatin receptors (SSTRs) 2 and 5. These receptors can be specifically targeted with a somatostatin peptide analogue (DOTATOC/DOTATATE) which can be chelated to a positron emission tomography (PET) emitting radioisotope such as Ga-68 for imaging or to a β-emitting radioisotope Lu-177 for therapy. A key advantage of this approach is that the receptor expression can be demonstrated by PET imaging before the patient is treated. Clinical studies in G1 and G2 GEP-NETS have demonstrated that PRRT is extremely effective in terms of progression free survival (PFS), symptom control and quality of life, with a well-established safety profile. A beneficial effect on outcome survival awaits to be confirmed. The first commercially available product Lu-177-DOTATATE was approved following the NETTER-1 trial in G1 and G2 GE-NETS. Lu-177-DOTATATE 7,4 GBq every 8 weeks for 4 cycles, together with octreotide LAR 30 mg monthly, demonstrated a median PFS of 28,4 months compared to 8,5 months for octreotide LAR 60 mg monthly. A second pivotal study COMPETE is currently in progress, comparing no carrier-added (n.c.a.) Lu-177-DOTATOC to the m-TOR inhibitor Everolimus in both GE-NETs and PNETs. Two studies, NETTER-2 and COMPOSE are currently underway in patients with high grade G2 and G3 NETs. Novel SSTR antagonists are being developed as next generation targeting molecules for SSTR2-expressing tumors. Antagonists have a higher tumor binding to receptors than agonists, opening up the potential indications for SSTR2 targeting to tumors which have a relatively lower expression of SSTR2 compared to NET such as small cell lung cancer, hepatocellular carcinoma and breast cancer. In addition to Lu-177, radioisotopes with different radiation properties such as Tb-161 and the α-emitter Ac-225 are being developed which have the potential to improve treatment efficacy across the range of G1 to G3 NETs.
Keywords: Ga-68 PET; Lutetium-177; dosimetry; neuroendocrine tumors (NETs); peptide receptor radionuclide therapy (PRRT); targeted radionuclide therapy (TRT).
Copyright © 2022 Harris and Zhernosekov.
Conflict of interest statement
PH and KZ are employees of ITM Oncologics GmbH.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/9659917/bin/fendo-13-941832-g001.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/9659917/bin/fendo-13-941832-g002.gif)
Similar articles
-
Radiopharmaceuticals used for diagnosis and therapy of NETs.Hell J Nucl Med. 2023 May-Aug;26 Suppl:19-20. Hell J Nucl Med. 2023. PMID: 37658556
-
Prediction of 177Lu-DOTATATE PRRT Outcome Using Multimodality Imaging in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Results from a Prospective Phase II LUMEN Study.J Nucl Med. 2024 Feb 1;65(2):236-244. doi: 10.2967/jnumed.123.265987. J Nucl Med. 2024. PMID: 38164576 Clinical Trial.
-
Combined use of 177Lu-DOTATATE and metronomic capecitabine (Lu-X) in FDG-positive gastro-entero-pancreatic neuroendocrine tumors.Eur J Nucl Med Mol Imaging. 2021 Sep;48(10):3260-3267. doi: 10.1007/s00259-021-05236-z. Epub 2021 Feb 18. Eur J Nucl Med Mol Imaging. 2021. PMID: 33604690 Free PMC article. Clinical Trial.
-
Radionuclide Therapy for Neuroendocrine Tumors.Curr Oncol Rep. 2017 Feb;19(2):9. doi: 10.1007/s11912-017-0567-8. Curr Oncol Rep. 2017. PMID: 28220446 Review.
-
Semi-automated segmentation methods of SSTR PET for dosimetry prediction in refractory meningioma patients treated by SSTR-targeted peptide receptor radionuclide therapy.Eur Radiol. 2023 Oct;33(10):7089-7098. doi: 10.1007/s00330-023-09697-8. Epub 2023 May 6. Eur Radiol. 2023. PMID: 37148355 Review.
Cited by
-
Liver-Directed Locoregional Therapies for Neuroendocrine Liver Metastases: Recent Advances and Management.Curr Oncol. 2024 Apr 5;31(4):2076-2091. doi: 10.3390/curroncol31040154. Curr Oncol. 2024. PMID: 38668057 Free PMC article. Review.
-
Current clinical application of lutetium‑177 in solid tumors (Review).Exp Ther Med. 2024 Mar 26;27(5):225. doi: 10.3892/etm.2024.12514. eCollection 2024 May. Exp Ther Med. 2024. PMID: 38596660 Free PMC article. Review.
-
Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives.EJNMMI Radiopharm Chem. 2024 Feb 6;9(1):9. doi: 10.1186/s41181-024-00239-1. EJNMMI Radiopharm Chem. 2024. PMID: 38319526 Free PMC article. Review.
-
An Overview of Advances in Rare Cancer Diagnosis and Treatment.Int J Mol Sci. 2024 Jan 18;25(2):1201. doi: 10.3390/ijms25021201. Int J Mol Sci. 2024. PMID: 38256274 Free PMC article. Review.
-
Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments.Theranostics. 2024 Jan 1;14(1):17-32. doi: 10.7150/thno.87345. eCollection 2024. Theranostics. 2024. PMID: 38164150 Free PMC article. Review.
References
-
- Fani M, Good S, Maecke HR. Radiometals (non-Tc, non-re) and bifunctional labeling chemistry. In: Handbook of nuclear chemistry. Dordrecht; Heidelberg; London; New York: Springer; (2011). p. 2143.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous