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Updated: Aug 22, 2025
Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
Published on: January 29, 2019
Optimisation of radioligand therapy in neuroendocrine tumours: Current and evolving evidence
Shaunak Navalkissoor1, Gopinath Gnanasegaran1, Ashley Grossman2
1Department of Nuclear Medicine, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust, London, UK.
Abstract:
Treatment of neuroendocrine tumours (NETs) with radioligand therapy (RLT) for example, 177 Lu-DOTATATE is generally well-tolerated and prolongs time to progression in most patients. However, approximately 20% of patients are nonresponders. In addition, complete responses are rare (<5% of patients), and durable responses beyond 3-4 years are uncommon. This article will discuss factors which may improve the outcomes of PRRT by using biomarkers to identify patients at high risk to be nonresponders (imaging and liquid biomarkers) and will examine mechanisms to potentially improve/optimise current RLT treatment strategies. These include mechanisms to potentiate the effects of RLT, increase tumour absorbed dose, overcoming radio-resistance and upregulation of somatostatin receptors, although larger studies will be required to demonstrate which techniques are going to be most efficacious in clinical practice.
Insights
Radioligand therapy (RLT) shows promise for neuroendocrine tumors (NETs), but outcomes vary. Biomarkers and novel strategies are crucial for improving patient response rates and treatment efficacy.
Area of Science:
- Oncology
- Nuclear Medicine
- Radiopharmaceutical Therapy
Background:
- Radioligand therapy (RLT), exemplified by 177 Lu-DOTATATE, is a standard treatment for neuroendocrine tumors (NETs).
- While generally well-tolerated and effective in prolonging progression-free survival for many, a significant portion of patients (approx. 20%) do not respond.
- Complete and durable responses to current RLT strategies remain uncommon.
Purpose of the Study:
- To explore strategies for enhancing the efficacy of peptide receptor radionuclide therapy (PRRT) for NETs.
- To identify biomarkers for predicting non-response to RLT.
- To examine novel mechanisms for optimizing current RLT treatment paradigms.
Main Methods:
- Review of current literature on RLT for NETs.
- Discussion of imaging and liquid biomarkers for predicting treatment outcomes.
- Exploration of potential therapeutic strategies to enhance RLT effectiveness.
Main Results:
- Identification of patient subgroups at high risk for non-response to RLT.
- Proposed mechanisms to potentiate RLT effects, including increasing tumor absorbed dose and overcoming radio-resistance.
- Strategies for somatostatin receptor upregulation are under investigation.
Conclusions:
- Biomarker-driven patient selection is key to improving RLT outcomes in NETs.
- Further research into novel therapeutic combinations and optimization techniques is warranted.
- Larger clinical studies are necessary to validate the efficacy of proposed RLT enhancement strategies.
