Novel Direct Alpha Spectroscopy Technique for $^{225}$Ac Radiopharmaceutical detection in Cancer Cells

Abstract

Targeted alpha-particle therapy (TAT) employs alpha-emitting radionuclides conjugated to tumor-targeting molecules to deliver localized radiation to cancer cells, showing great promise in treating metastatic cancers. Among these radionuclides, Actinium-225 ($^{225}$Ac, t$_{1/2}$ = 9.9 days) has emerged as a clinically promising candidate. Its decay chain generates four successive alpha emissions, resulting in highly localized and effective cytotoxic damage to cancer cells when delivered to tumor sites. However, the assumption of complete retention of $^{225}$Ac and its radioactive daughters at these target sites is often inaccurate. The nuclear recoil effect can lead to off-target distribution and unintended toxicity. Our results revealed distinct spectral differences between radiolabeled cells and reference samples, demonstrating [$^{225}$Ac]Ac-crown-TATE uptake by AR42J cells. Detection of $^{213}$Po, one of the $^{225}$Ac decay daughters, highlighted partial retention and release of decay products from cells, providing information on intracellular retention and daughter redistribution. Geant4 simulations confirmed the alignment of experimental data with theoretical models, validating the method's accuracy. This study establishes a direct alpha spectroscopy approach for investigating $^{225}$Ac and its daughters' behavior in cells and offers a powerful tool for microdosimetry estimation.