Magnesium-28: A Novel Self-Theranostic Approach through Targeting Metabolic Enzyme Disruption and Intracellular Radiation.
The limitations of conventional cancer therapies, such as low selectivity and significant side effects, necessitate innovative approaches. This study proposes a pioneering self-theranostic strategy using Magnesium-28 (Mg-28) alone, enabling simultaneous diagnosis, therapy, and therapy control. Exploiting the elevated Mg2+ demand in cancer cells, Mg-28 self-targets Mg-dependent enzymes (e.g., DNA/RNA polymerases, hexokinase, telomerase) within intracellular organelles like the nucleus and mitochondria, without bio-chemical carriers or nanoparticles as recently methods. A theoretical model, based on the Mg-uptake coefficient, predicts selective Mg-28 accumulation in tumors following intravenous administration. The Mg-28 chain decays into Aluminum-28 then Silicon-28, delivering highly localized irradiation via beta particles, Auger electrons, and recoil ions to critical intracellular structures, while disrupting essential Mg-dependent enzymes for a dual mechanism of radiotherapy and multi-enzyme inactivation. Simulations of Linear Energy Transfer (LET), radiation range, and absorbed dose show that nanogram-scale amounts of Mg-28 can deliver 60-400 Gy to tumors ranging from 0.03 mg to 500 g in size, suggesting potential cytotoxicity that could be effective across not only a broad range of stages but also types of cancer due to the fundamental role of magnesium in cancer cell metabolism and proliferation. Mg-28 and its daughters gamma emissions support early tumor detection and real-time treatment monitoring, enhancing precision. As the first proposed single-isotope theranostic approach leveraging magnesium dependency, this innovative strategy provides a robust foundation for future preclinical and clinical investigations aimed at validating its therapeutic efficacy, pharmacokinetics, and biosafety inaugurating a novel hypothesis for cancer therapy.