Page 85 - TD-4-3

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

modalities that may only detect larger tumor masses. matrix metalloproteinases (MMPs) impairs the ability of
Traditional methods usually diagnose cancer at the cancer cells to invade surrounding tissues and metastasize.
milligram scale using PET-computed tomography (CT) or By disrupting key metabolic enzymes, such as hexokinase,
SPECT-CT. 2,8,9 kinases, and ATPases, Mg-28 deprives cancer cells of
Moreover, the continuous uptake of Mg-28 by tumor essential energy, leading to metabolic collapse and necrosis.
cells, sustained throughout the treatment period, facilitates Beta-minus particles, despite their lower LET, have a
real-time monitoring of therapeutic response. Changes longer range that allows them to traverse larger cellular
in Mg-28 concentration within the tumor, as visualized distances, generating free radicals along their path. These
through imaging, can provide immediate feedback on free radicals can indirectly damage DNA, proteins, and
treatment efficacy, allowing for timely adjustments to the other cellular components, contributing to the overall
therapeutic regimen. This dual diagnostic and therapeutic cytotoxic effect of Mg-28. The combined action of direct
(theranostic) functionality, achieved with a single isotope, bond breakage by high-LET particles and indirect damage
simplifies the clinical workflow and eliminates the need by free radicals ensures a multifaceted attack on essential
for paired diagnostic and therapeutic agents, representing cellular machinery.
a key advantage of the Mg-28 method. Current methods Targeted irradiation within the nucleus and
often use two or more radioactive isotopes for diagnosis mitochondria is achieved through the selective uptake
and treatment monitoring, such as Tc-99m + Y-90 or of Mg-28, where crucial Mg-dependent enzymes, such
Tc-99m + Lu-177 with SPECT-CT, and F-18 + Y-90 or as DNA/RNA polymerases, hexokinase, and telomerase
F-18 + Lu-177 with PET-CT. 2,8,9 reside. The subsequent decay of Mg-28 directly induces

4.3. Enzyme inactivation and intracellular localized irradiation through beta particles, Auger
irradiation electrons, and recoil ions, resulting in a concentrated
release of damaging particles close to their molecular
Data from Table 2 reveal the LET and range of the particles targets, thus maximizing enzyme inactivation and cellular
emitted during Mg-28 decay. Auger electrons exhibit destruction. Traditional inhibitors or modern methods
3-7
the highest LET (0.81–1.6 eV/Å), followed by recoil usually use one inhibitor for one specific enzyme or one
ions (0.1–0.21 eV/Å), while beta-minus particles have a biochemical agent for one determined molecular target.
lower LET (0.002–0.09 eV/Å) but a much longer range
(0.07–6.11 mm). 4.4. Precision targeting and safety profile
The high LET of Auger electrons and recoil ions is The distinct ranges of the emitted particles from Mg-28
particularly significant for enzyme inactivation and decay contribute to its precision targeting and favorable
intracellular damage. As shown in Table 3, the energy safety profile. The very short range of recoil ions
deposited by these particles per unit length is sufficient (0.022–1.5 Å) ensures that their destructive energy is
to break various critical biological bonds, including the deposited within nanometer distances, primarily affecting
relatively strong covalent bonds, such as S-S (disulfide) the enzyme molecules in their immediate vicinity. Auger
and P-O (in ATP/ADP), as well as weaker non-covalent electrons, with a slightly longer range (88–224 nm), also
bonds, such as Van der Waals and hydrogen bonds deposit their energy within the subcellular compartments,
that are crucial for maintaining the three-dimensional causing localized damage to organelles, such as the nucleus
structure and function of enzymes and DNA. The recoil and mitochondria.
of Al-28 and Si-28 ions, although occurring over a very In contrast, the longer range of beta-minus particles
short range (0.022–1.5 Å), can directly disrupt the active (up to 6.11 mm) might suggest the potential for off-target
sites of enzymes due to the momentum transfer and local effects. However, the preferential uptake of Mg-28 by
structural distortion. These effects, together with the cancer cells, as indicated by the high Mg-uptake coefficient,
difference in charge and ionic radius from Mg to Al to concentrates the source of these beta particles within the
3+
2+
Si , will certainly inactivate Mg-dependent enzymes once tumor tissue. Furthermore, the energy deposition per unit
4+
Mg-28 replaces stable Mg in these enzymes. Specifically, length (LET) of beta-minus particles is lower compared
the inactivation of DNA/RNA polymerases, helicase, to Auger electrons and recoil ions, meaning that while
topoisomerase, and DNA repair enzymes disrupts or they can travel further, the density of ionization events
arrests the S phase of the cell cycle, leading to apoptosis. along their path is less intense. This localized delivery of
Targeting telomerase prevents cancer cells from achieving radiation, particularly the high-LET emissions within
immortality, thus limiting tumor growth and reducing the the tumor cells, minimizes the exposure of surrounding
potential for invasion. Furthermore, the inactivation of healthy tissues to significant radiation doses.

Volume 4 Issue 3 (2025) 77 doi: 10.36922/TD025070010