Page 80 - TD-4-3

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

Silicon-28 (Si-28), with emissions capable of disrupting the available nuclear data. 17,25 Modeled scenarios assumed the
function of these critical enzymes in cancer cells. 17 administration of Mg-28 in doses ranging from 0.1 to 6.2 ng
and included three delivery scenarios: (1) Intravenous
2.2. Mechanism of Mg-dependent enzyme injection without tumor-specific uptake, (2) intravenous
inactivation injection with high tumor-specific uptake (based on the Mg
Mg typically stabilizes the active sites of Mg-dependent uptake coefficient of tumor cells), and (2) direct injection
2+
enzymes by forming six-coordinate bonds with oxygen into the tumor. In addition, absorbed doses were evaluated
atoms from carboxylate and phosphate groups. 18-21 This for different treatment regimens involving 62, 300, and
coordination is essential for substrate binding and catalytic 400 Mg-28 ions/cell. These correspond to different levels
activity. Upon radioactive decay, Mg-28 transforms of inhibition, with the aim of inactivating approximately
into Al and then Si , both of which possess higher 300 Mg-dependent enzymes.
3+
4+
charges and smaller ionic radii (Al : 0.50 Å; Si : 0.40 Å) 2.5. Tumor-specific Mg uptake
4+
3+
compared to Mg (0.72 Å). 22,23 This substitution disrupts
2+
2+
the electrostatic interactions within the active site, leading The selective accumulation of Mg by cancer cells,
to structural stress, distortion, weakened substrate compared to their normal counterparts, forms the
binding, and ultimately, impaired or abolished catalytic foundation for employing the radioisotope Mg-28 in
efficiency. In addition, the recoil of Al-28 and Si-28 ions targeted cancer therapy. This differential uptake arises
during decay (with a displacement of 0.022–1.5 Å) can primarily from the significantly higher replication rates
cause local distortions at the enzyme active site. Given the of cancerous tissues, leading to an increased demand for
2+
precise spatial requirements for enzymatic catalysis, such Mg —a crucial cofactor for numerous enzymes involved
displacements can further impair enzyme functionality. in DNA replication, protein synthesis, and energy
The high-LET particles (beta particles and Auger metabolism. 11,20 Although intracellular concentrations
2+
electrons) emitted during decay also contribute to enzyme of stable Mg may be similar in individual normal and
inactivation by breaking covalent and non-covalent bonds cancerous cells, the dynamic process of rapid cell division
2+
within the apoenzyme and generating free radicals that leads to a significantly greater overall Mg uptake at the
denature surrounding proteins. tissue level in tumors.
To quantify this difference, we model the reproductive
2.3. LET and radiation range
capacity of healthy and cancerous tissues over time. The
The LET and the range of beta particles, Auger electrons, proliferation of healthy and cancerous tissues can be
and recoil ions emitted during Mg-28 decay were calculated using Equations II and III, respectively, while the
calculated using the NIST ESTAR program and Medical growth ratio between the two types of tissues is expressed
24
Internal Radiation Dose (MIRD) data. 17,25 For recoil ions as in Equation IV.
(Al-28 and Si-28), recoil energies were derived using
Equation I, based on the principle of conservation of HealthytissueA: 2 ( n a ) n t T (II)
;
a
momentum following beta particle emission from the a
parent Mg-28 nucleus. n b )
Cancer tissueB 2 ( ; n t (III)
:
E 2 b T b
E recoil (I)
2 Mc 2 B 2 n b 2 t 1 Tb 1 Ta ) (IV)
(
n a
where E recoil is the recoil energy of the daughter A
nucleus (Al-28 or Si-28); E is the energy of the emitted where A and B are the number of healthy cells and
β
beta particle; M is the mass of the daughter nucleus; and cancer cells, respectively; n and n are the number of
b
a
c = 9 ×10 m /s is the square of the speed of light. doubling periods of healthy tissue and cancerous tissue,
2
2
2
16
respectively; t is the actual copy time; and T and T are
a
b
These resulting energy values were then used to model the replication cycle of healthy cells and cancer cells,
the LET and range of these recoil ions in different tissue respectively.
types.
By introducing the doubling time ratio k = T /T , which
b
a
2.4. Absorbed dose calculations reflects the differences in cell division dynamics, Equation
Absorbed dose calculations were performed for tumors IV can be transformed to Equation V.
of different volumes (T –T ) and for the whole body of a B t T b 11( k / )
0
5
60-kg individual using the MIRD program and publicly A 2 (V)
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Volume 4 Issue 3 (2025) 72 doi: 10.36922/TD025070010