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Tumor Discovery Mg-28-A theoretical novel strategy in cancer therapy

The absence of a need for bulky biochemical carriers flexibility in dosing regimens allows for tailored treatment
or nanoparticles further enhances the precision and safety strategies based on tumor characteristics and patient-
of Mg-28 therapy. As a naturally recognized ion, Mg-28 specific factors.
is efficiently transported into cancer cells, ensuring direct
intracellular irradiation without the complexities and 4.6. Summary of key advantages
potential drawbacks of exogenous delivery systems. This The Mg-28 therapy presents a transformative and
intrinsic targeting mechanism contributes to the high biologically intelligent approach to cancer treatment,
local dose within the tumor while minimizing systemic offering several key advantages that distinguish it from
toxicity. conventional modalities.

4.5. High local dose with minimal systemic toxicity 4.6.1. Dual mechanism of action for enhanced efficacy
Simulation results using the MIRD code (Table 4) By simultaneously targeting multiple critical
demonstrate the potential of Mg-28 to deliver a high Mg-dependent enzymes essential for cancer cell survival
absorbed dose to tumors while maintaining minimal and proliferation (DNA/RNA polymerases, hexokinase,
systemic toxicity. The calculations, performed over 21 h telomerase, and MMPs) and delivering highly localized
(approximately one half-life of Mg-28), considered different intracellular irradiation through its decay products (beta
treatment regimens based on the number of Mg-28 ions particles, Auger electrons, and recoil ions), Mg-28 offers
internalized per cancer cell. a synergistic therapeutic effect. This can overcome drug
Assuming a regimen of 400 Mg-28 ions/cell (regimen f), resistance and achieve comprehensive tumor control—a
a tumor absorbed dose of 415 Gy can be achieved across all key advantage over single-target traditional inhibitors.
tumor stages (T –T ). This dose is significantly above the 4.6.2. Intrinsic and highly selective tumor targeting
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generally accepted therapeutic threshold of around 50 Gy
required for effective tumor control. Notably, the total The therapy leverages the inherent metabolic vulnerability
amount of Mg-28 needed to deliver this high local dose is of cancer cells, characterized by their rapid proliferation
remarkably small, with a maximum of only 6.2 ng required and elevated demand for Mg. The quantified Mg-uptake
for even the largest T tumors. This high efficacy at the coefficient demonstrates a significant preferential
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nanogram scale underscores the potency and economic accumulation of Mg-28 within tumor tissues, eliminating
viability of the Mg-28 approach. the need for complex and potentially toxic biochemical
Conversely, the corresponding whole-body absorbed carriers or nanoparticles. This natural targeting mechanism
dose for the same regimen (regimen f) remains ensures a high concentration of the therapeutic agent
consistently low, with a maximum of 2.33 Gy observed directly within the tumor microenvironment.
for the smallest T tumors, decreasing to the mGy range 4.6.3. Integrated self-theranostic capability
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for larger tumors (e.g., 59.2 mGy for T and 5.92 mGy for
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T ). This significant disparity between the high local tumor Mg-28 uniquely combines diagnostic and therapeutic
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dose and the low systemic exposure highlights the inherent functionalities within a single radioisotope, embodying
safety advantage of Mg-28 therapy, minimizing potential a self-theranostic approach. Its gamma emissions
damage to healthy organs and tissues. allow for early tumor detection using PET or SPECT
imaging—even at microscopic stages—while its continuous
The enhanced Mg uptake by cancer cells, driven by uptake facilitates real-time monitoring of treatment
their elevated metabolic and replicative demands, further response, enabling personalized and adaptive therapeutic
contributes to this favorable dose distribution. This strategies without the need for additional agents.
biological preference ensures that Mg-28 is selectively
concentrated within the tumor microenvironment, 4.6.4. Maximized local efficacy with minimized
maximizing the therapeutic effect while sparing normal systemic toxicity
cells. Simulation data indicate that Mg-28 can deliver cytotoxic
The data in Table 4 also illustrate the dose-response radiation doses directly to tumor cells at the nanogram
relationship with varying numbers of Mg-28 ions/cell scale, while the absorbed dose to surrounding healthy
(regimens d, e, and f). Even with lower intracellular tissues remains remarkably low. This favorable therapeutic
concentrations of Mg-28 (62 and 300 ions/cell), index is attributed to the selective tumor uptake and the
therapeutically relevant tumor doses (60.1 Gy and 312 Gy, short-range, high-LET emissions of its decay products,
respectively) can be achieved with correspondingly lower which concentrate the destructive energy within the tumor
systemic exposure and amounts of Mg-28 required. This volume.

Volume 4 Issue 3 (2025) 78 doi: 10.36922/TD025070010