en.Wedoany.com Reported - The radioconjugate ATNM-400 demonstrated superior antitumor activity compared to existing PSMA-targeted radiotherapy drugs and androgen receptor pathway inhibitors (ARPIs) in preclinical models of prostate cancer. The findings were presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) annual meeting.
In a low-PSMA-expressing prostate cancer 22Rv1 cell line xenograft model, ATNM-400, developed by Actinium Pharmaceuticals, achieved 94.29% tumor growth inhibition (TGI) as a monotherapy at a dose of 40 μCi/kg. Comparative data showed that Novartis' 177Lu-PSMA-617 (Pluvicto) as a monotherapy at 40 mCi/kg resulted in a TGI of 5.12%, while the combination of this dose with enzalutamide at 25 mg/kg/day achieved a TGI of 54.88%.
In a comparative study with second-generation ARPIs, ATNM-400 at 40 μCi/kg achieved a TGI of 94.3% in the 22Rv1 in vivo model, compared to Johnson & Johnson's apalutamide (Erleada) at 50 mg/kg/day with a TGI of 31.9% and Bayer's darolutamide (Nubeqa) at 100 mg/kg/day with a TGI of 5.1%. When ATNM-400 at 40 μCi/kg was combined with either ARPI, at least 57% of tumor-bearing mice achieved a complete treatment response.
Lead study author Sumit Mukherjee (M.Sc., Ph.D.), Chief Scientist and In Vivo Biology Manager at Actinium Pharmaceuticals, along with colleagues, noted that ATNM-400 demonstrated superior and durable antitumor activity in prostate cancer models resistant to approved ARPIs and PSMA-targeted radiotherapy. The researchers stated that the drug's mechanism of action, which triggers alpha particle-mediated double-strand DNA (dsDNA) breaks and subsequent apoptosis of target tumor cells, may provide a rational option for addressing treatment resistance in prostate cancer. Mukherjee's team added that ATNM-400 offers a mechanism-based strategy by targeting tumor proteins associated with disease progression and treatment resistance, with an action mode distinct from PSMA-directed and tumor microenvironment-targeting approaches.
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