177Lu-DOTA-LM3 – a novel radionuclide therapy proven safe and effective to treat neuroendocrine neoplasms (NEN)

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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-in-human study utilized ¹⁷⁷Lu-DOTA-LM3 therapy, which was administered without severe adverse effects and was well tolerated by the majority of patients. This research was published in the November issue of The Journal of Nuclear Medicine (see citing below).

Conclusion: The antagonist PRRT with ¹⁷⁷Lu-DOTA-LM3 could be administered without severe adverse effects and was well tolerated by most patients, with thrombocytopenia occurring in only a few. No other severe adverse effects were observed; in particular, there was no nephrotoxicity. The SSTR antagonist ¹⁷⁷Lu-DOTA-LM3 appears to be promising for PRRT, provides a favourable biodistribution and higher tumour radiation doses than SSTR agonists, and was effective in treating advanced metastatic NENs, especially in patients with low or no SSTR agonist binding, even achieving complete remission in some patients.

First-in-Humans Study of the SSTR Antagonist ¹⁷⁷Lu-DOTA-LM3 for Peptide Receptor Radionuclide Therapy in Patients with Metastatic Neuroendocrine Neoplasms: Dosimetry, Safety, and Efficacy

Richard P. Baum, Jingjing Zhang, Christiane Schuchardt, Dirk Müller and Helmut Mäcke 

Journal of Nuclear Medicine November 2021, 62 (11) 1571-1581; DOI: https://doi.org/10.2967/jnumed.120.258889

Interest Point

A similar trial but using a different radionuclide called [¹⁶¹Tb]Tb-DOTA-LM3 forms part of a NET Research Foundation sponsored research completed in Dec 2025.  The key distinction between [¹⁶¹Tb]Tb-DOTA-LM3 and [177Lu]-DOTA-LM3 is that they behave almost identically pharmacokinetically, but [¹⁶¹Tb]-LM3 delivers substantially more lethal dose to single tumour cells and small clusters because of its additional conversion and Auger electrons. This makes it a potentially more powerful SSTR2‑antagonist PRRT agent, especially for micrometastatic disease. Read more about this – click here or on the photo below.

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