In 2021, NETRF funded Paul Schaffer, PhD, of the University of British Columbia, for a pilot project entitled “Preclinical Toxicity and Therapy Study of 225Ac-crown-TATE.” The study’s outcomes were recently published in the journal Nuclear Medicine and Biology.
This study highlights a promising advancement in treating somatostatin receptor-2 (SSTR2) positive neuroendocrine tumors using a novel targeted alpha therapy approach. Traditional peptide receptor radionuclide therapy (PRRT) with beta-emitting Lutathera (Lu-177-DOTA-TATE) has shown clinical efficacy, but alpha-emitting Actinium (Ac)-225 has emerged as a potentially stronger therapeutic candidate. However, a significant challenge with Ac-225 therapy has been the need for harsh conditions to attach the radioactive material to the tumor-targeting molecule. This can limit its effectiveness and increase unwanted side effects.
The study by Dr. Schaffer and his team introduces a new molecule, [225Ac]Ac-crown-TATE, which aims to improve upon DOTA-TATE by offering milder radiolabeling conditions, greater stability, and higher tumor uptake while reducing off-target accumulation in normal tissues. In preclinical mouse models, [225Ac]Ac-crown-TATE demonstrated sustained tumor uptake, reduced toxicity, and significant improvement in survival compared to controls.
These findings underscore the importance of next-generation alpha-emitting PRRT agents that could enhance treatment efficacy and patient outcomes. Further clinical investigations could position [225Ac]Ac-crown-TATE as a game-changing therapy for neuroendocrine tumor patients, particularly those resistant to current treatments.
This work also highlights NETRF’s significant role in building and sustaining the pipeline of neuroendocrine cancer researchers. Dr. Schaffer stated, “Personally, this grant was the first grant I secured as a new investigator back in 2021. It allowed me to hire my first postdoc and get my research program started. I will always cherish the memory of the excitement when I heard this proposal was funded.”
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