A new form of radionuclide therapy for peptide receptors (PRRT) has been proven to control the progression of disease in 85 percent of patients with neuroendocrine tumors that have metastatic spread, and achieving complete remission in a few patients. The 177LuDOTA-LM3 therapy was used in the first-in-human clinical study. It was well-tolerated and had no serious adverse reactions. The study was published in The Journal of Nuclear Medicine.
Neuroendocrine Neoplasms are cancers that result from diffuse neuroendocrine system cells. They are most common in the gastrointestinal tract as well as the pancreas. Neuroendocrine tumors are relatively rare , but their incidence and prevalence have increased significantly in recent decades. Neuroendocrine tumors that are overexpressing somatostatin receptors, or SSTRs, are most common. These receptors are utilized for imaging and treatment.
SSTR-targeted imaging using radiolabeled Somatostatin agonists followed by PRRT has proven extremely effective in managing neuroendocrine tumours in the last 20 years. However, potent SSTR antagonists-;which only poorly internalize into tumor cells if they do so at all–have been found to be even superior to agonists for such purposes.”
Jingjing Zhang, MD, PhD, Assistant Professor, Department of Diagnostic Radiology at the Yong Loo Lin School of Medicine, National University of Singapore in Singapore
To further investigate the role antagonists can play in the treatment of neuroendocrine tumors, researchers conducted a study to determine the safety, biodistribution, and efficiency of a new type of SSTR antagonist, 177Lu-DOTA-LM3. 51 patients with progressive, heavily pretreated neuroendocrine tumors underwent PRRT using 177Lu-DOTA-LM3. Treatment-related adverse events were rated for all participants and dosimetry was conducted for 11 patients.
177 Lu-DOTA-LM3 was administered without severe adverse effects and was well tolerated by most patients. Disease control was achieved in 40 of 47 patients (85 percent) who were monitored after 177Lu-DOTA-LM3 treatment. Two patients were completely cured by the European Organization for Research and Treatment of Cancer criteria.
It is important to note that the dosimetry and uptake of the antagonist 177Lu–DOTA-LM3 was compared to the more widely used SSTR agonist 177Lu–DOTATOC in patients receiving the same dosimetry protocol. 177Lu–DOTA-LM3 had a higher uptake and shorter effective half-life tumors, which resulted in higher radiation doses than the antagonist 177Lu–DOTATOC.
“These positive results demonstrate the feasibility and superiority of SSTR antagonist 177Lu-DOTA-LM3 as compared to SSTR agonists. Additionally, antagonist PRRT can be performed under concurrent treatment with somatostatin analogues , without having to stop these medications. This is especially crucial for patients suffering from carcinoid disease or even carcinoid crisis.” said Richard P. Baum, MD PhD who is the president of the academy at the International Centers for Precision Oncology (ICPO) and consultant for the Center for Advanced Radiomolecular Precision Oncology, CURANOSTICUM Wiesbaden-Frankfurt both located in Germany. “The results are very encouraging for theranostic applications of SSTR antagonists to improve the outcomes of patients suffering from neuroendocrine tumors in the future.”
The study was made available on the internet in March 2021.
Baum, R.P., and. (2021) First-in-Humans Study of the SSTR Antagonist 177Lu-DOTA LM3 for Peptide Receptor Radionuclide Therapy in patients suffering from Metastatic Neuroendocrine Neoplasms: Dosimetry, Safety, and effectiveness. Journal of Nuclear Medicine. doi.org/10.2967/jnumed.120.258889.
Content Source: https://www.news-medical.net/news/20211123/Study-proves-safety-and-effectiveness-of-novel-radionuclide-therapy-for-neuroendocrine-neoplasms.aspx