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Clinical application of targeted α-emitter therapy in gastroenteropancreatic neuroendocrine neoplasms
Naoyuki Yamaguchi1, Jing-Jing Wei2,3,4, Hajime Isomoto5
1Department of Endoscopy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan.
Abstract:
Effective therapeutic strategies for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remain challenging, including a lack of response to therapy and post-treatment relapse. The rapid development of targeted radionuclide therapy (TRT) offers promising data for patients with somatostatin receptor (SSTR)-expressing tumors. This approach exhibits more advantages than somatostatin analog (SSA) therapy, which is primarily effective for well-differentiated and slow-growing GEP-NENs. Fortunately, some clinical studies on peptide receptor radionuclide therapy (PRRT) labeled with α-emitting radionuclides for GEP-NENs patients showed effective results for those with more advanced GEP-NENs, or those with malignant metastasis. For the improvement of clinical efficacy and the decline in the incidence of treatment-related relapse, recent progress in developing novel techniques and effective disease management strategies for optimal targeting has led to the emergence of targeted alpha therapy (TAT) in GEP-NENs patients. For instance, labeled technology and combination therapy could contribute to significantly improved long-term outcomes. However, the exact dosimetry for precision oncology, the shortage of radionuclides, and the stability of disease control are still under careful consideration. More high-quality, large-scale prospective studies are essential for obtaining valuable evidence on challenging problems and for further exploration.
Insights
Targeted radionuclide therapy (TRT) shows promise for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Targeted alpha therapy (TAT) offers improved efficacy and reduced relapse for GEP-NENs patients, though further research is needed.
Area of Science:
- Oncology
- Nuclear Medicine
- Radiopharmaceutical Therapy
Background:
- Advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) present therapeutic challenges, including treatment resistance and relapse.
- Somatostatin analog (SSA) therapy is limited to well-differentiated, slow-growing GEP-NENs.
- Targeted radionuclide therapy (TRT) shows potential for SSTR-expressing tumors.
Purpose of the Study:
- To review the emergence and potential of targeted alpha therapy (TAT) for GEP-NENs.
- To highlight advancements in novel techniques and disease management for optimal targeting.
- To discuss challenges and future research directions in TAT for GEP-NENs.
Main Methods:
- Review of clinical studies on peptide receptor radionuclide therapy (PRRT) with alpha-emitting radionuclides.
- Analysis of recent progress in targeted alpha therapy (TAT) development for GEP-NENs.
- Discussion of labeled technology and combination therapy approaches.
Main Results:
- PRRT with alpha-emitting radionuclides has shown effectiveness in advanced GEP-NENs and metastatic disease.
- Novel techniques and disease management strategies are improving TAT efficacy and reducing relapse.
- Combination therapies and advanced labeling technologies show potential for improved long-term outcomes.
Conclusions:
- Targeted alpha therapy (TAT) represents a promising advancement for managing advanced GEP-NENs.
- Further high-quality, large-scale prospective studies are essential to address dosimetry, radionuclide availability, and disease control stability.
- TAT offers potential for improved clinical efficacy and reduced treatment-related relapse in GEP-NENs patients.
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