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A model for experimental interstitial radiotherapy using intracerebral D-54MG glioma xenografts in athymic mice

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Abstract

Due to its constant glial morphology and small variability as to tumor location and growth characteristics, the intracerebral D-54MG tumor xenograft provides the predictability and reproducability needed by models for the study of stereotactic interstitial radiotherapy. Development and results of experimental brachytherapy in an intracerebral human gliomas derived xenograft tumor model are reported. Tumor homogenate prepared from homogenized subcutaneous D-54MG xenografts was inoculated into the frontal lobe of athymic BALB/c mice (nu/nu genotype). The D-54MG glioma xenografts grew at the site of inoculation without intraventricular or subarachnoid spread. The increase of median survival (IMS) was 58.33% for the highest dose (9370 cGy) and 33.3% for the intermediate dose (5654 cGy). In both experiments the survival prolongation was statistically significant (p<0.05) as calculated by the Log Rank Rest for Kaplan Meier Survival Distributions. In the low dose group (3159 cGy) only a small and not significant IMS was achieved (16.67%). The results of the present investigation demonstrate the accuracy of the stereotactic operative procedure and the efficacy of experimental intracerebral interstitial radiotherapy with I125 seeds. Using a constant dose rate, experimental interstitial brachytherapy in brain-tumor bearing nude mice was shown to result in a dose dependant survival prolongation for the treated animals. The model may help to optimize the rational basis of clinical brain tumor therapy and is well suited to simulate dose and dose rate related therapeutic effects.

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References

  1. Ajuriaguerra JDE, P Benda, J Constans, M David, M Tubiana: Etude experimentale des lesions provoquees par l'implantation intracerebrale de fragments d'or radioactif. Revue Neurologique 91, No. 4 (1954) 260–264

    Google Scholar 

  2. Bering EA Jr., OT Bailey, OT Fowler, PH Dillard, FD Ingraham: The effect of gamma radiation on the central nervous system: II The effects of localized irradiation from tantalum 182 implants. AJR 74 (1955) 686–700

    Google Scholar 

  3. Bernstein M, PH Gutin, DF Deen, KA Weaver, VA Levin, MH Barcellos: Radiosensitization of the RIF-1 murine flank tumor by desmethylmisonidazole (Ro 05 9963) during interstitial radiotherapy. Int J Radiation Oncology Biol Phys 8 (1982) 487–490

    Google Scholar 

  4. Bigner SH, J Mark, DD Bigner: Chromosomal composition of four permanent cultured cell lines derived from human gliomas. Cancer Genet Cytogenet 10 (1983) 335–349

    Google Scholar 

  5. Borison HL, SC Wang: Quantitative effects of radon implanted in the medulla oblongata: A technique for producing discrete lesions. J Comp Neurol 94 (1951) 33–55

    Google Scholar 

  6. Bullard DE, SC Schold, SH Bigner, DD Bigner: Growth and chemotherapeutic response in athymic mice of tumors arising from human glioma-derived cells lines. J Neuropath Exp Neurology 40 (1981) 410–427

    Google Scholar 

  7. Clayton BE, WA Langmead, JM Wordon: Implantation of radioactive yttrium in the pituitary fossa of the guinea pig. Br J Radiol 34 (1961) 120–128

    Google Scholar 

  8. DaSilva V, PH Gutin, DF Deen, KA Weaver: Relative biological effectiveness of I-125 sources in a murine brachytherapy model. Int J Radiation Oncology Biol Phys 10 (1984) 2109–2111

    Google Scholar 

  9. Davies L, SL Goldstein: The therapeutic use of the radioactive isotopes in intracranial tumors. Ann Surg 136 (1952) 381–391

    Google Scholar 

  10. Edwards DJ, HJ Bagg: Lesion of the corpus striatum by radium emanation and the accompanying functional and structural changes. Am J Physiol 65 (1923) 162–173

    Google Scholar 

  11. El-Hennawi Y, GY Gillespie, MS Mahaley Jr, MA Varia, DD Bigner, C Stanton: A controlled study of efficacy of interstitial or external irradiation in a virus-induced brain-tumor model in rats. J Neurosurg 71 (6) (1989): 898–902

    Google Scholar 

  12. Fike JR, CE Cann, TL Phillips, M Bernstein, PH Gutin, K Turowski, KA Weaver, RL Davis, RJ Higgins, V DaSilva: Radiation brain damage induced by interstital I-125 sources: a canine model evaluated by quantitative computed tomography. Neurosurgery 16, No. 4 (1985) 530–537

    PubMed  Google Scholar 

  13. Fu KK, TL Philipps, LJ Kane, V Smith: Tumor and normal tissue response to irradiation in vivo: Variation with decreasing dose rates. Radiology 114 (1975) 709–716

    Google Scholar 

  14. Fu KK, S Hurst, AC Begg, JM Brown: The effects of misonidazole during continous low dose rate irradiation. Cancer Clin Trials 3 (1980) 257–265

    Google Scholar 

  15. Giard DJ, SA Aaronson, GJ Todaro, P Arnstein, JH Kersey, H Dosile, WP Parks: In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst (1973) 1417–1423

  16. Globus JH, SC Wang, HI Maibach: Radon implatation in the medulla oblongata of the dog: Effects on the degree and extent of cellular reactions. J Neuropathol Exp Neurol 11 (1952) 429–442

    Google Scholar 

  17. Groothuis DR, DC Wright, CB Ostertag: Sequential changes of capillary permeability in normal canine brain associated with I-125 interstitial radiotherapy (1993)

  18. Haymaker W, G Laqueur, WJH Nauta, JE Pickering, JC Sloper, FS Vogel: The effects of barium 140-lanthanum 140 (gamma) radiation on the central nervous system and pituitary gland of macaque monkees: A study of 67 brains and spinal cords and 77 pituitary glands. J Neuropathol Exp Neurol 17 (1958) 12–57

    Google Scholar 

  19. Horsley V, NS Finzi: Action of filtered radium rays when applied directly to the brain. Br Med J 2 (1991) 898

    Google Scholar 

  20. Janzer RC, P Kleihues, CB Ostertag: Early and late effects on the normal dog brain of permanent interstitial Iridium-192 irradiation. Acta Neuropathologica (Berl) 70 (1986) 91–102

    Google Scholar 

  21. Kim JH, BS Hilaris: Iodine 125 source in interstitial tumor therapy — clinical and biological considerations. AJR 123, No. 1 (1975) 163–169

    Google Scholar 

  22. Kobayashi T, Y Kida, M Matsui, Y Amemiya: Interstitial hyperthermia of malignant brain tumors using implant heating system (IHS). No Shinkei Geka 18 (3) (1990) 247–252

    Google Scholar 

  23. Krishnaswamy V: Dose distribution around an I-125 seed source in tissue. Radiology 126 (1978) 489–491

    Google Scholar 

  24. Ling CC, MC Schell, ED Yorke, BB Palos, DO Kubiatowitz: Two-dimensional dose distribution of I-125 seeds. Med Phys 12 (5) (1985) 652–655

    Google Scholar 

  25. Lippitz BE, EC Halperin, Griffith OW, OM Colvin, G Honore, CB Ostertag, DD Bigner, HS Friedman: L-buthionine-Sulfoximine Mediated Radiositization in Experimental Intestitial Radiotherapy of Intracerebral D-54MG Glioma Xenografts in Athymic Mice. Neurosurgery 26 (2) (1990) 255–260

    Google Scholar 

  26. Ostertag CB, D Groothuis, P Kleihues: Experimental data on early and late morphologic effects of permanently implanted gamma and beta sources (Iridium-192, Iodine-125, and Yttrium-90) in the brain Acta Neurochir, Suppl 33 (1984) 271–280

    Google Scholar 

  27. Ostertag CB, P Warnke P Kleihues, DD Bigner: Iodine-125 interstitial irradiation of virally induced dog brain tumors. Neurological Research 6 (1984) 176–180

    Google Scholar 

  28. Ostertag CB, K Weigel, P Warnke, G Lombeck, P Kleihues: Sequential changes in the dog brain after interstitial iodine-125 irradiation. Neurosurg 13 (5) (1983) 523–528

    Google Scholar 

  29. Ostertag CB, KA Hossmann, W v d Kerckhoff: Radiation effects of Iridium 192 implants in the cat brain. Nuklearmedizin 21 (1982) 99–104

    Google Scholar 

  30. Pendergrass EP, JM Hayman Jr, KM Houser, VC Rambo: The effects of radium on the normal tissues of the brain and spinal cord of dogs and its therapeutic application. AJR 9 (1922) 553–569

    Google Scholar 

  31. Ross JP: The treatment of cerebral tumors with radium. Br J Surg 18 (1931) 618–635

    Google Scholar 

  32. Weizsaecker M, DF Deen, ML Rosenblum, T Hoshino, PH Gutin, M Barker: The 9L rat brain tumor: description and application of an animal model. J Neurol 224 (1981) 183–192

    Google Scholar 

  33. Williamson CS, O Brown, JW Butler: A study of the effects of radium on normal brain tissue. A preliminary report. Surgery Gynec Obstet 31 (1920) 239–242

    Google Scholar 

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  1. Department of Neurosurgery, Technical University of Aachen, Fed. Rep. of Germany

    Bodo E. Lippitz

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Lippitz, B.E. A model for experimental interstitial radiotherapy using intracerebral D-54MG glioma xenografts in athymic mice. Neurosurg. Rev. 18, 259–264 (1995). https://doi.org/10.1007/BF00383877

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  • DOI: https://doi.org/10.1007/BF00383877

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