Study Proves Safety and Effectiveness of New Radionuclide Therapy for Neuroendocrine Neoplasms

A new type of peptide receptor radionuclide therapy (PRRT) has been shown to control disease in 85 percent of patients with metastatic neuroendocrine neoplasms, achieving complete remission in some patients. The first human study used 177Lu-DOTA-LM3 therapy, which was administered without serious side effects and was well tolerated by the majority of patients. This research was published in the November issue of The Journal of Nuclear Medicine.

Neuroendocrine neoplasms are tumors that arise from diffuse cells of the neuroendocrine system. They are most often found in the gastrointestinal tract, pancreas, and lungs. Neuroendocrine neoplasms are quite rare diseases, but their incidence and prevalence have increased dramatically in recent decades. The majority of neuroendocrine tumors overexpress somatostatin receptors (SSTRs), which are targeted for imaging and treatment.

Over the past two decades, SSTR-targeted imaging using radiolabeled somatostatin agonists followed by PRRT has been remarkably effective in the management of neuroendocrine tumors. However, potent SSTR antagonists, which internalize poorly in tumor cells, if at all, have been surprisingly shown to be superior to agonists for such purposes. “

Jingjing Zhang, MD, PhD, Assistant Professor, Department of Diagnostic Radiology at Yong Loo Lin School of Medicine, National University of Singapore in Singapore

To further investigate the role that antagonists may play in treating neuroendocrine tumors, researchers developed a study to determine the safety, biodistribution, and efficacy of a new type of SSTR antagonist, 177Lu-DOTA-LM3. Fifty-one patients with heavily pretreated progressive neuroendocrine neoplasms underwent PRRT with 177Lu-DOTA-LM3. Treatment-related adverse events were classified for all participants and dosimetry was performed for 11 patients.

177Lu-DOTA-LM3 was administered without serious side effects and was well tolerated by most patients. Disease control was achieved in 40 of 47 patients (85%) who were followed up after 177Lu-DOTA-LM3 therapy. Two patients achieved complete remission according to the criteria of the European Organization for Research and Treatment of Cancer.

Note, the absorption and dosimetry of the antagonist 177Lu-DOTA-LM3 were compared with those of the commonly used SSTR agonist 177Lu-DOTATOC in patients treated according to the same dosimetry protocol. 177Lu-DOTA-LM3 demonstrated higher absorption and a longer effective half-life in tumor lesions, resulting in higher tumor radiation doses than for the agonist 177Lu-DOTATOC.

“These encouraging results demonstrate the feasibility and superiority of the SSTR antagonist 177Lu-DOTA-LM3 versus SSTR agonists. In addition, antagonistic PRRT can be performed under concomitant treatment with somatostatin analogues without the need to discontinue these drugs. This is especially important for patients with carcinoid syndrome or even carcinoid crisis, ”said Richard P. Baum, MD, PhD, academy president of the International Centers for Precision Oncology (ICPO) and consultant for the Center. for Advanced Radiomolecular Precision Oncology. , CURANOSTICUM Wiesbaden-Frankfurt, both in Germany. “The results are very encouraging for theranostic applications of SSTR antagonists to further improve outcomes in patients with neuroendocrine neoplasms in the future. “

This study was posted online in March 2021.

Source:

Society of Nuclear Medicine and Molecular Imaging

Journal reference:

Baum, RP, et al. (2021) First human study of the SSTR 177Lu-DOTA-LM3 antagonist for peptide receptor radionuclide therapy in patients with metastatic neuroendocrine neoplasms: dosimetry, safety and efficacy. Journal of Nuclear Medicine. doi.org/10.2967/jnumed.120.258889.

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