Accumulation of Boron in Human Malignant Glioma Cells in vitro is Cell Type Dependent
- 94 Downloads
It has been shown that human malignant glioma tumours consist of several subpopulations of tumour cells. Due to heterogeneity and different degrees of vascularisation cell subpopulations possess varying resistance to chemo- or radiation therapy. Therefore, therapy is dependent on the ability to specifically target a tumour cell. Boron neutron capture therapy (BNCT) is a bimodal method, in radiation therapy, taking advantage of the ability of the stable isotope boron-10 to capture neutrons. It results in disintegration products depositing large amounts of energy within a short length, approximately one cell diameter. Thereby, selective irradiation of a target cell may be accomplished if a sufficient amount of boron has been accumulated and hence the cell-associated boron concentration is of critical importance. The accumulation of boron, boronophenylalanine (BPA), was investigated in two human glioma cell subpopulations and a human fibroblast cell line in vitro. The cells were incubated at low boron concentrations (0–5 μg B/ml). Oil filtration was then used for separation of extracellular and cell-associated boron. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used for boron determination. Significant (P < 0.05) differences in accumulation ratio (relation between cell-associated and extracellular boron concentration) between human malignant glioma cell lines were found. Human fibroblasts, used to represent normal cells, showed a growth-dependent uptake and a lower accumulation ratio than the glioma cells. Our findings indicate that BPA concentration, incubation time and differences in boron uptake between cell subpopulations should be considered in BNCT.
Unable to display preview. Download preview PDF.
- 2.Nistér M, Wedell B, Betsholtz C, Bywater M, Pettersson M, Westermark B, Mark J: Evidence for progressional changes in the human malignant glioma line U-343MGa: analysis of karyotype and expression of genes encoding the subunit chains of platelet-derived growth factor. Cancer Res 47: 4953–4960, 1987PubMedGoogle Scholar
- 3.Shapiro JR, Mehta BM, Ebrahim SAD, Scheck AC, Moots PL, Fiola MR: Tumor heterogeneity and intrinsically chemoresistant subpopulations in freshly resected human malignant gliomas. In: Sudilovsky O et al. (eds) Boundaries between Promotion and Progression during Carcinogenesis. Plenum Press, New York, 1991Google Scholar
- 7.Fukuda H, Hiratsuka J, Honda C, Kobayashi T, Yoshino K, Karashima H, Takahashi J, Abe Y, Kanda K, Ichihashi M, Mishima Y: Boron neutron capture therapy of malignant melanoma using 10B-paraboronophenylalanine with special reference to evaluation of radiation dose and damage to normal skin. Radiat Res 138: 435–442, 1994PubMedGoogle Scholar
- 8.Fukuda H, Honda C, Wadabayashi N, Kobayashi T, Yoshino K, Hiratsuka J, Takahashi J, Akaizawa T, Abe Y, Ichihashi M, Mishima Y: Pharmacokinetics of 10B-p-boronophenylalanine in tumours, skin and blood of melanoma patients: a study of boron neutron capture therapy for malignant melanoma. Melanoma Res 9: 75–83, 1999PubMedGoogle Scholar
- 9.Chanana AD, Capala J, Chadha M, Coderre JA, Diaz AZ, Elowitz EH, Iwai J, Joel DD, Liu HB, Ma R, Pendzick N, Peress NS, Shady MS, Slatkin DN, Tyson GW, Wielopolski L: Boron neutron capture therapy for glioblastoma multiforme: interim results from the phase I/II dose-escalation studies. Neurosurgery 44: 1182–1193, 1999PubMedCrossRefGoogle Scholar
- 10.Busse PM, Harling OK, Palmer MR, Kiger WS, Kaplan J, Kaplan I, Chuang CF, Goorley JT, Riley KJ, Newton TH, Santa Cruz GA, Lu X-Q and Zamenhof RG: A critical examination of the results from Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease. J Neurooncol 62: 111–121, 2003PubMedCrossRefGoogle Scholar
- 11.Capala J, Stenstam H.-B, Sköld K, Munck af Rosenschöld P, Giusti V, Persson C, Wallin E, Brun A, Franzen L, Carlsson J, Salford L, Ceberg C, Persson B, Pellettieri L, Henriksson R: Boron neutron capture therapy for glioblastoma multiforme: clinical studies in Sweden. J Neurooncol 62: 135–144, 2003PubMedCrossRefGoogle Scholar
- 12.Joensuu H, Kankaanranta L, Seppala T, Auterinen I, Kallio M, Kulvik M, Laakso J, Vahatalo J, Kortesniemi M, Kotiluoto P, Seren T, Karila J, Brander A, Jarviluoma E, Ryynanen P, Paetau A, Ruokonen I, Minn H, Tenhunen M, Jaaskelainen J, Farkkila M, Savolainen S: Boron Neutron Capture Therapy of brain tumours: clinical trials at the Finnish facility using boronophenylalanine. J Neurooncol 62: 123–134, 2003PubMedCrossRefGoogle Scholar