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"Radiosensitisers and Radioprotectors"

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Methotrexate

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RADIOBIOLOGICAL ASPECTS

Dose
Modification
Ratio[DMF]:
Studies
related
to DMF :
Transfection of HOS osteosarcoma cells with RAD51 gene decreased cellular sensitivity to methotrexate and γ-rays. The sensitizer enhancement ratios after irradiation in combination with methotrexate were 1.51 and 0.99, respectively.[1]

Test System Dose of radiation Drug Conc. Time of Drug administration DMF/qualitative
radiomodification
Reference
human breast cancer cells, MDA-MB-231 111In-NLS-trastuzumab (~0.2 MBq/mg, 100 nmol/L) by IC 10 = 1.01 +/- 0.01 µmol/L concurrent treatment RER(survival) = 1 [2]
human breast cancer cells, 231-H2N IC 10 = 12.0 +/- 0.23 µmol/L RER(survival) = 2.2
human breast cancer cells,, TrR1 IC 10 = 0.01 +/- 0.001 µmol/L RER(survival) = 2
human breast cancer cells, TrR2 IC 10 = 1.13 +/- 0.16 µmol/L RER(survival) = 1
human breast cancer cells, MDA-MB-231, 231-H2N, TrR1, TrR2 111In-NLS-trastuzumab (1–450 nmol/L; 190 +/- 8.9 MBq/mg) 0.001 - 100 µmol/L for 24 hrs, concurrent treatment radiosensitization [3]
Adult female Sprague-Dawley rats 1600 cGy to 3200 cGy Methotrexate was infused into CSF at rate of 0.5 ul/hr for 14 days
1.6 X 10-6 molar in CSF
before irradiation Reduction in radiation-induced white matter necrosis
DMF = 1.09
[4]
nude rats bearing TE671 human rhabdomyosarcoma tumours (7.4 MBq), 5-[125I]iodo-2’-deoxyuridine every other day, 6 administrations 31 µg methotrexate, intrathecal, every other day, 6 administrations on alterate days delay in the onset of paralysis [5]
X- irradiation
Female WAG/Rij rats 20 Gy, cranial irradiation 25 mg/kg body wt, IV At different times (l- 15 days) after the radiation exposure change in permeability of blood-brain barrier for methotrexate, lasting for 9 days [6]
Sprague-Dawley rats 600-1400 cGy Intraventricular methotrexate, 4 mg/kg body weight 30-45 min before irradiation DMF (reduction in the number of cells with small dark nuclei in subependymal plate) = 1.44
DMF (reduction in the mitotic count in in subependymal plate) = 1.25
[7]
137Cs- irradiation
Nasal NK/T-cell lymphoma cell lines (Hank-1 and NK-92) 0-7 Gy 30-150 nM inhibition of cell viability and induction of apoptosis [8]
Fractionation study:
REFERENCES
1. Du L et al, Correlation of RAD51 and radiosensitization of methotrexate. Chinese Journal of Radiological Medicine and Protection 2012;32(1): 44-46.
https://inis.iaea.org/search/search.aspx?orig_q=RN:46111314
2. Costantini DL et al, Methotrexate, Paclitaxel, and Doxorubicin radiosensitize HER2-Amplified human breast cancer cells to the Auger electron–emitting radiotherapeutic agent 111In-NLS-Trastuzumab. J Nucl Med 2010; 51:477–483.
http://dx.doi.org/10.2967/jnumed.109.069716
3. Costantini DL et al, Trastuzumab-resistant breast cancer cells remain sensitive to the Auger electron–emitting radiotherapeutic agent 111In-NLS-Trastuzumab and are radiosensitized by Methotrexate. J Nucl Med 2008; 49:1498–1505.
http://dx.doi.org/10.2967/jnumed.108.051771
4. Geyer JR et al, Radiation, methotrexate, and white matter necrosis: laboratory evidence for neural radioprotection with preirradiation methotrexate.Int J Radiat Oncol Biol Phys. 1988 ;15(2):373-5.
http://dx.doi.org/10.1016/S0360-3016(98)90018-9
5. Kassis AI et al, Therapeutic potential of 5-[125I]iodo-2’-deoxyuridine and methotrexate in the treatment of advanced neoplastic meningitis. Int J Radiat Biol 2004;80(11–12): 941–946.
http://dx.doi.org/10.1080/09553000400017671
6. Storm AJ, van der Kogel AJ, Nooter K, Effect of X-irradiation on the pharmacokinetics of Methotrexate in rats: alteration of the blood-brain barrier. Eur J Cancer Clin Oncol. 1985 ;21(6):759-64.
http://dx.doi.org/10.1016/0277-5379(85)90275-5
7. Morris AD, Hopewell JW, Combined effects of radiation and methotrexate on the cells of the rat subependymal plate. J R Soc Med. 1983 ;76(10):848-52.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1439615/
8. Kim A et al, A combination of methotrexate and irradiation promotes cell death in NK/T-cell lymphoma cells via down-regulation of NF-kB signaling. Leukemia Research 2012;36:350-357.
http://dx.doi.org/10.1016/j.leukres.2011.07.027