Page 13 - ARNM-1-2

Advances in Radiotherapy
& Nuclear Medicine Advancements and challenges in radioactive iodine-125

radiobiology and dose prescription rules, such as the Paris Repopulation is a phenomenon that impacts rapidly
system, has been obtained using low-dose-rate irradiation proliferating normal tissues and tumors, serving as a
(dose rates ranging from 40 to 100 cGy/h). Radiation- compensatory mechanism for radiation-induced cell
induced cell damage leading to cell death included death. The linear-quadratic model is primarily focused on
potentially lethal and sublethal damages. cell death, where the dose-effect relationship is linear at low
doses due to directly lethal damage and becomes quadratic
The radiobiological mechanisms of brachytherapy were
poorly understood, with available data mainly focused on at higher doses due to sublethal damage. However, when
examining the radiobiology of brachytherapy specifically,
[35]
dose-rate effects . In brachytherapy, where dose rates the role of proliferation is generally minimal, except in
typically range from 0.3 Gy/h to 1 Gy/min, DNA repair cases involving treatments lasting several weeks, as seen
is an important parameter in determining cell lethality. with I-125 seed permanent implants. Therefore, I-125 seeds
Isoeffect dose-response curves published in the 1980s may not be suitable for rapidly proliferating tumors with
demonstrated the dose-rate effect: A physical dose of 60 Gy high α/β values . The level of tumor hypoxia exhibits an
[44]
delivered at 1 cGy/min (0.6 Gy/h) was radiobiologically inverse correlation with the probability of tumor control.
equivalent to a total dose of 30 Gy delivered at 10 cGy/min Hypoxic tumors can be identified through perfusion MRI
(6 Gy/h) . Measurements of sublethal damage indicated and specific tracers, and their presence can be correlated
[36]
a concomitant increase in dose rate and residual double- with histological findings (hypoxia-inducible factor-1
stranded DNA breaks at the same total dose, resulting in a expression), tumor genomic analysis, and prognosis .
[45]
decrease in the surviving fraction in clonogenic assays . In low-dose-rate treatments spanning several days, the
[37]
The negative effect of decreasing dose rates on LC was also contribution of reoxygenation is minimal.
observed in a cohort of 340 breast cancer patients receiving
brachytherapy increments. Patients with dose rates of 0.3 The biological effective dose (BED) is a measure of
[46]
– 0.4 Gy/h experienced 31% of local recurrences, whereas the biological effect of radiation . BED enables the
those with dose rates of 0.8 – 0.9 Gy/h had no local comparison of different irradiation regimens. One study
recurrences . Thus, while low-dose-rate brachytherapy introduces a method to use BED for comparing and
[38]
offers advantages, it also has limitations in terms of the integrating dose data from both EBRT and interstitial I-125
therapeutic index. brachytherapy components in the treatment of prostate
cancer. This involves converting the dose distributions
I-125 brachytherapy, a form of continuous LDR of conformal EBRT and conventional interstitial I-125
brachytherapy, relies on the radioactivity of I-125 seeds. At brachytherapy into the common “language” of BED
a dose rate of 1 Gy/h, its efficacy is equivalent to that of 2 Gy distributions, facilitating the comparison and integration
fractionated radiotherapy. Human tumor cell lines exhibit of radiation treatment plans for prostate cancer . In the
[47]
a wide range of radiosensitivity to LDR brachytherapy at context of I-125 brachytherapy with conventional doses,
1 Gy/h. This variability may arise from clustered ionizing the relative biological effect is 1.4, and the dose rate is
events causing DNA damage or damage to hyper-sensitive approximately 0.07 Gy/h. This profile appears to be more
genomic regions . A study compared clonogenic survival suitable for treating radiosensitive tumors with long
[39]
in 27 human tumor cell lines with varying genotypes doubling times and rapid shrinkage [48,49] . Therefore, the
after exposure to LDR or HDR irradiation. The study also optimal application of I-125 brachytherapy may depend
assessed susceptibility to LDR-induced redistribution in on selecting tumors that are relatively radiosensitive
the cell cycle in eight of these cell lines. The results indicate and where late responses are dose-limited in anatomical
[50]
that the radiosensitivity of human tumor cells to both LDR sites . It is worth noting that an increasing number of
and HDR irradiation is genotype-dependent , and cell studies are reporting equivalent efficacy between HDR
[40]
[41]
radiosensitivity varies across different cell cycle phases . and LDR brachytherapy. In cases of fast-growing tumors,
For I-125 brachytherapy in gastric tumor xenografts, HDR brachytherapy might offer more advantages than
increased apoptosis within tumors was reported, along LDR brachytherapy due to enhanced cellular repair
with G2/M cell arrests. This was accompanied by an capacity [51-53] .
increase in intratumor expression of vascular endothelial
growth factor and nuclear factor-kappa B in tumor 4. Physics of I-125 brachytherapy
neovessels . Furthermore, compared to 6 MV X-rays with Brachytherapy implementation hinges on several critical
[42]
a dose rate of 4 Gy/min, I-125 brachytherapy with a dose factors, including the application of specialized dosimetric
rate of 2.77 cGy/h demonstrated more effective induction systems to calculate treatment duration and dosage, the
of cell apoptosis and G2/M cell cycle arrest in colon cancer calibration of radioactive sources, and the monitoring of
cells . seed positioning for geometric accuracy.
[43]

Volume 1 Issue 2 (2023) 5 https://doi.org/10.36922/arnm.0914