III.1. Results
The findings stemming from the analysis of magnesium content within both cancerous and healthy tissue samples of the same type are meticulously presented in Table 2. Within this table, we have meticulously computed magnesium content and the corresponding activity of Mg-28 within hypothesized stage 2a cancer tissue samples, each of a size ≤ 7cc. Table 3 is dedicated to showcasing simulated absorbed dose values linked to various radioactive isotopes frequently employed in cancer treatment—namely Lu-177, Y-90, I-131—alongside Mg-28. These calculations encompass the gastrointestinal route (via stomach, small intestine) as well as the respiratory route (inhalation), all at an identical activity level of 19.7 MBq. These discernments are concisely summarized in Table 4.
Table 5 is dedicated to simulated absorbed dose values for 0.1 ng of Mg-28, presenting distinct avenues of entry into the body. On the other hand, Table 6 furnishes calculated absorbed dose values for 0.1 ng of Mg-28 following intravenous injection across various organs and tumor masses of varying dimensions, subsequent to a 21-hour interval. The nomenclature employed ranges from T1 to T4 for tumor masses not exceeding 7cc in size, and T5 to denote a 500cc mass.
According to the insights presented in Table 6, intravenous injection of Mg-28 without a concurrent tumor mass leads to widespread distribution across diverse organs, akin to scenario (5d). This scenario assumes the delivery of Mg-28 to organs via the circulatory system (6a), retention within the residual body portion (6b), and dose dispersion across varying tumor masses (6c), (6d), (6e), (6f), (6g), (6h). Notably, figures (6i) and (6k) provide a visualization of dose distribution within tumor mass T5, incorporating intravenous injection, with consideration for bladder retention and the residual body portion. Of particular significance, figure (6h) postulates a scenario where Mg-28 is directly introduced into tumor mass T5.
Table 2. Magnesium ion content in the analyzed samples, magnesium content in stage 2A samples, and the equivalent activity of Mg-28 for effective dose calculation in tissues.
Sample Code
|
Tissue Sample Name
|
Result (mg/kg)
|
Mg content in stage 2a (ng)
|
Equivalent activity of Mg-28 (MBq)
|
DV (22) 4199 A’
|
Breast Cancer
|
16,11 ± 1,21
|
0,11 ± 0,01
|
22,22 ± 0,32
|
DV (22) 4199 A
|
Breast Cancer
|
14,52 ± 1,12
|
0,10 ± 0,01
|
19,72 ± 0,51
|
DV (22) 4194 A’
|
Breast Cancer
|
14,31 ± 1,32
|
0,09 ± 0,01
|
17,73 ± 0,22
|
DV (22) 4194 A
|
Breast Cancer
|
11,81 ± 1,04
|
0,08 ± 0,01
|
15,73 ± 0,23
|
DV (22) 4199-L’
|
Healthy Breast Tissue
|
16,92 ± 1,51
|
0,12 ± 0,04
|
23,62 ± 0,31
|
DV (22) 4199-L
|
Healthy Breast Tissue
|
7,62 ± 3,52
|
0,05 ± 0,01
|
9,82 ± 0,54
|
DV (22) 4161-21A’
|
Cervix Uteri
|
54,53 ± 3,81
|
0,38 ± 0,05
|
78,42 ± 0,72
|
DV (22) 4161-21A
|
Cervix Uteri
|
50,94 ± 3,52
|
0,35 ± 0,03
|
68,92 ± 0,64
|
DV (22) 4648 -LNC’
|
Healthy Colon
|
38,62 ± 3,03
|
0,27 ± 0,02
|
53,14 ± 0,52
|
DV (22) 4648-LNC
|
Healthy Colon
|
43,03 ± 3,31
|
0,30 ± 0,03
|
59,14 ± 0,43
|
DV (22) 4648-ANC’
|
Colon Cancer
|
41,72 ± 4,23
|
0,29 ± 0,04
|
57,15 ± 0,61
|
DV (22) 4648-ANC
|
Colon Cancer
|
55,71 ± 5,13
|
0,39 ± 0,04
|
74,82 ± 0,72
|
Table 4. Absorbed dose per unit activity (mGy/MBq) for oral ingestion into the stomach of the four isotopes Lu-177, Mg-28, Y-90, and I-131.
|
Lu-177 (T1/2=6,7d)
|
Mg-28 (T1/2=21h)
|
Y-90 (T1/2=2,67 d)
|
I-131 (T1/2=8,06d)
|
Stomach
|
2,64 E+02
|
2,93 E+02
|
4,06 E+02
|
2,85 E+02
|
Muscle
|
7,51 E+01
|
9,33 E+01
|
2,74 E+02
|
9,72 E+01
|
Tongue
|
2,41 E+01
|
3,63 E+01
|
1,17 E+02
|
3,36 E+01
|
Please note that the absorbed dose values in mGy/MBq are given for each tissue/organ and for each isotope. The values provided are in scientific notation format (E+02 represents 10^2, E+01 represents 10^1, etc.).
III.2. Discussion.
Observing the data in column 3 of Table 2, it becomes evident that the magnesium content in tumor masses and healthy tissues shows minimal variance, aligning within the range of 7.62 to 16.92 ppm in breast tissue and 38.62 to 55.71 ppm in colon tissue. These values adhere consistently to established references [68-73]. Meanwhile, column 4 of the same table details the magnesium quantities in stage 2A tumors, and column 5 computes the corresponding Mg-28 activity. Hence, the magnesium ion content within the three categories of stage 2A tumors spans from 0.1 to 0.4 nanograms. Notably, assuming that 0.1 ng of Mg-28 can engage in competition with magnesium within cancer cells at an exceedingly low probability (1‰), it could potentially deactivate 2.15 x 10^9 enzymes reliant on magnesium ions as cofactors. It's worth mentioning that highlighted values belonging to healthy tissues within the table can be disregarded. Additionally, the value of 0.1 ng of Mg-28, corresponding to 19.7 MBq or 0.53 mCi of radiation as deduced from equation (2), yields effective dose values suitable even for substantial tumor masses, while inflicting minimal impact on critical healthy tissues such as the heart, lungs, uterus, liver, kidneys, and spleen (as reflected in Tables 5 and 6).
A careful examination of Table 3 reveals the disposition of radioactive substances—Lu-177 (3a), Mg-28 (3b), Y-90 (3c), and I-131 (3d)—following oral administration after 21 hours (spanning a half-life of Mg-28 for comparison). These substances predominantly accumulate within the stomach. Disparities emerge solely in terms of dosage (MBq/mGy), with Y-90 displaying elevated doses in the stomach, muscle, and tongue compared to the remaining three isotopes. Corresponding reference values are outlined in Table 4.
Upon consulting Table 5, it's evident that the distribution of Mg-28 activity within the body after 21 hours significantly varies based on the chosen administration pathways. Orally or inhalationally introduced Mg-28 primarily concentrates its radiation impact on tissues such as the stomach, small intestine, and lungs. This phenomenon is attributed mainly to beta radiation, with gamma radiation exerting minimal influence (scenarios 5a, 5b, and 5c). In contrast, the distribution pattern shifts when Mg-28 is introduced intravenously, leading to its relatively widespread distribution across diverse organs. The absorbed dose calculation encompasses contributions from both beta and gamma radiation (scenario 5d). Consequently, for tumors located within the digestive and respiratory organs, oral ingestion or inhalation could be the preferred administration routes. Conversely, for tumors in other internal organs, intravenous injection might be a more suitable choice.
Further insight can be gleaned from the scenario where Mg-28 is solely administered intravenously after 21 hours. In this instance, blood serves as the medium for transporting and dispersing Mg-28 to various organs, as demonstrated in Figure 6a. This distribution proves relatively comprehensive, with the absorbed dose being relatively modest, approximately 12 mGy per injection per organ. In scenarios where the residual body portion retains Mg-28, the distribution pattern aligns with Figure 6b, concentrating within adipose and muscle tissues. Here, the absorbed dose is even smaller, approximating 800 mGy per injection. As fat and muscle tissues constitute roughly 50-60% of body weight and boast a widespread presence, the concentration of Mg-28 within these tissues incurs minimal impact on crucial organs. Hence, this dose could be deemed safe for the body. Consequently, administering 0.1 ng of Mg-28 aligns with radiation exposure safety considerations.
Analyzing the absorbed dose distribution of Mg-28 within various tumor masses underscores its stability and a direct correlation with tumor size. The absorbed dose values are delineated as follows: U1: 3.21 x 10^5 mGy, U2: 3.2 x 10^4 mGy, U3: 3.02 x 10^3 mGy, U4: 3.18 x 10^2 mGy, U5: 5.34 mGy/MBq. Evidently, the smaller the tumor mass, the higher the absorbed dose, owing to the mass reduction.
Absorbed dose, as defined, is the radiation energy absorbed per unit mass of the material it traverses.
Here:
- dD is the absorbed dose calculated in Gy and has the dimension J/kg (Joules per Kilogram).
- dQr is the radiation energy of a decay, measured in eV or multiples of eV such as keV, MeV, or GeV. In the case of isotopes located inside, the energy loss from the body due to highly penetrating gamma or X-rays is negligible compared to the portion absorbed by high-energy charged particles. Therefore, dQr can be considered as the radiation energy absorbed. It should be noted that 1 eV = 1.6 x 10^-19 J.
- dm is the mass of the material through which the radiation passes, measured in kg.
Hence, it becomes evident that the smaller the tumor mass, the higher the absorbed dose, yielding a more pronounced interaction between radiation and the tumor mass. In the case of U5, direct delivery of Mg-28 to the tumor mass without intravenous injection sustains the absorbed dose at 5.34 mGy/MBq, mirroring the outcome of intravenous injection. However, notable differences arise in other organs such as adipose tissue, muscle tissue, and the bladder, where radiation retention is absent. This point underscores a crucial consideration: if a means of directly delivering Mg-28 to the tumor mass can be devised, potential side effects could be minimized.
Shifting focus to tumor masses T1 through T4, the absorbed dose of Mg-28 showcases considerable elevation, holding the potential to eliminate cancer cells with a single injection. The absorbed dose values per injection are outlined as follows: T4: 6000 mGy/0.1 ng Mg-28; T3: 60000 mGy/0.1 ng Mg-28; T2: 600000 mGy/0.1 ng Mg-28; and T1: 6000000 mGy/0.1 ng Mg-28. This signifies a delivery of concentrated radiation, rendering it possible to effectively eradicate cancer cells. This advantage of Mg-28 can be attributed to its identity as the Mg+2 ion, which serves as a cofactor in nearly 300 types of enzymes within cells. Given the rapid proliferation of cancer cells, their increased demand for magnesium ions in comparison to normal cells underscores the potential efficacy of this approach.
Further analysis reveals that the absorbed dose primarily results from the emission of beta particles. These particles exhibit a limited range of impact, spanning less than 3.6 mm in water. As a result, the surrounding healthy tissues adjacent to the tumor mass receive effective protection. This aspect highlights yet another remarkable advantage offered by Mg-28. Thus, enzymes reliant on magnesium ions as cofactors emerge as the prime targets for Mg-28 radioisotopes. Conversely, upon reaching their intended destination, these isotopes transform into agents capable of dismantling these very enzymes.
For stage 2A tumors, conforming to our previous assumption, they fall within the category of T4 tumor masses. Consequently, the utilization of Mg-28 can yield an impressively high absorbed dose, approximating 6000 mGy for a mere 0.1 ng of Mg-28. This dosage proves sufficiently potent to obliterate the entire cancerous mass. Even for larger tumors surpassing the confines of stage 2A, an option is to amplify the Mg-28 dosage by a factor of 10, resulting in an approximate value of 5.3 mCi or 197 MBq. This step is taken with the expectation of yielding improved outcomes. Nonetheless, it's crucial to underscore that this viewpoint necessitates empirical validation through experiments.
Please note that the table provides descriptions of the pathways of administering 19.7 MBq of Mg-28 into the body, namely through the stomach (5a), lungs (5b), small intestine (5c), and intravenous injection (5d).