A Study of The Assessment for Boron Neutron Capture Therapy Agent

  • Isman Mulyadi Triatmoko Center of Science and Technology of Accelerator; National Nuclear Energy Agency
  • Sutjipto Sutjipto Center of Science and Technology of Accelerator; National Nuclear Energy Agency
Keywords: BNCT, ICP-MS, MTT assay, TEM, IC50


A study of the assessment criteria covers the synthesis and characterization of agent and test their biological effectiveness as boron neutron capture therapy (BNCT) agents in cancer treatment. The cellular uptake of this agent into the glioblastoma cells was assessed by boron analysis (ICP-MS) and by fluorescence imaging (confocal microscopy). The agent enters the glioblastoma cells exhibiting a similar profile, i.e., preferential accumulation in the cytoskeleton and membranes and a low cytotoxic activity (IC50 values higher than 200 μM). The cytotoxic activity and cellular morphological alterations after neutron irradiation in the Research Reactor (>107 neutrons cm−2 s−1) were assessed by the MTT assay and by electron microscopy (TEM). Post neutron irradiation revealed that BNCT has a higher cytotoxic effect on the glioblastoma cells. Results provide a strong rationale for considering one of these compounds as a lead candidate for a new BNCT agent.


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A. C. Fernandes, J. P. Santos, J. G. Marques, A. Kling, A. R. Ramos and N. P. Barradas (2010), Validation of the Monte Carlo model supporting core conversion of the Portuguese Research Reactor (RPI) for neutron fluence rate determinations, Ann. Nucl. Energy, 37, 1139–1145.

A. Crivello, C. Nervi, R. Gobetto, S. G. Crich, I. Szabo, A. Barge, A. Toppino, A. Deagostino, P. Venturello and S. Aime (2009), Towards improved boron neutron capture therapy agents: evaluation of in vitro cellular uptake of a glutamine-functionalized carborane, J. Biol. Inorg. Chem.,14, 883–890.

A. H. Soloway, R. F. Barth, R. A. Gahbauer, T. E. Blue and J. H. Goodman (1997), The rationale and requirements for the development of boron neutron capture therapy of brain tumors, J. Neurooncol.,33, 9–18.

A. Irles, I. C. Gonçalves, M. C. Lopes, A. C. Fernandes, A. G. Ramalho and J. Pertusa (2001), A biological study on the effects of high and low LET radiations following boron neutron capture reaction at the Portuguese Research Reactor, Phys. Med.,17, 17–19.

A. Omuro and L. M. DeAngelis (2013), Glioblastoma and other malignant gliomas: a clinical review, JAMA, 310, 1842–1850.

A. Paul, P. Sengupta, Y. Krishnan and S. Ladame (2008), Combining G-Quadruplex Targeting Motifs on a Single Peptide Nucleic Acid Scaffold: A Hybrid (3+1) PNA-DNA Bimolecular Quadruplex, Chem. – Eur. J.,14, 8682– 8689.

A. Wittig, R. L. Moss and W. A. Sauerwein (2014), Glioblastoma, brain metastases and soft tissue sarcoma of extremities: Candidate tumors for BNCT, Appl. Radiat. Isot.,88, 46–49.

C. Caruso, M. Carcaterra and V. Donato (2013), Role of radiotherapy for high grade gliomas management, J. Neurosurg. Sci., 57, 163–169.

C. Fernandes, I. C. Gonçalves, J. Santos, J. Cardoso, L. Santos, A. F. Carvalho, J. G. Marques, A. Kling, A. J. G. Ramalho and M. Osvay (2006), Dosimetry at the Portuguese Research Reactor using thermoluminescent measurements and Monte Carlo simulations, Radiat. Prot. Dosimetry,120, 349–353.

C. H. Hsieh, Y. F. Chen, F. D. Chen, J. J. Hwang, J. C. Chen, R. S. Liu, J. J. Kai, C. W. Chang and H. E. Wang (2005), Evaluation of pharmacokinetics of 4-borono- 2-18F-fluoro-L- Phenylalanine for boron neutron capture therapy in a glioma-bearing rat model with hyperosmolar blood-brain barrier disruption, J. Nucl. Med.,46, 1858–1865.

C. P. Tanase, A. M. Enciu, S. Mihai, A. I. Neagu, B. Calenic and M. L. Cruceru (2013), Anti-cancer Therapies in High Grade Gliomas, Curr. Proteomics, 10, 246–260.

C. Viñas i Teixidor (2013), The uniqueness of boron as a novel challenging element for drugs in pharmacology, medicine and for smart biomaterials, Future Med. Chem.,5, 617–619.

D. R. Lu, S. C. Mehta and W. Chen (1997), Selective boron drug delivery to brain tumors for boron neutron capture therapy, Adv. Drug Delivery Rev., 26, 231–247.

E. L. Crossley, E. J. Ziolkowski, J. A. Coderre and L. M. Rendina (2007), Boronated DNA- binding compounds as potential agents for boron neutron capture therapy, Mini- Rev. Med. Chem.,7, 303–313.

E. Vega-Avila and M. K. Pugsley (2011), An Overview of Colorimetric Assay Methods Used to Assess Survival or Proliferation of Mammalian Cells, Proc. West. Pharmacol. Soc.,54, 10–14.

G. Cholewiński, K. Dzierzbicka and A. M. Kolodziejczyk (2011), Natural and synthetic acridines/acridones as antitumor agents: their biological activities and methods of synthesis, Pharmacol. Rep.,63, 305–336.

I. B. Sivaev and V. V. Bregadze (2009), Polyhedral Boranes for Medical Applications: Current Status and Perspectives, Eur. J. Inorg. Chem.,1433–1450.

J. Bonjoch, M. G. Drew, A. González, F. Greco, S. Jawaid, H. M. Osborn, N. A. Williams and P. Yaqoob (2008), Synthesis and evaluation of novel boron-containing complexes of potential use for the selective treatment of malignant melanoma, J. Med. Chem.,51, 6604–6608.

J. Kaur and P. Singh (2011), ATP selective acridone based fluorescent probes for monitoring of metabolic events, Chem. Commun.,47, 4472–4474.

J. Yoo and Y. Do (2009), Synthesis of stable platinum complexes containing carborane in a carrier group for potential BNCT agents, Dalton Trans.,4978–4986.

M. A. Pisarev, M. A. Dagrosa and G. J. Juvenal (2007), Boron neutron capture therapy in cancer: past, present and future, Arq. Bras. Endocrinol. Metabol.,51, 852–856.

M. Koba and T. Baczek (2011), Physicochemical interaction of antitumor acridinone derivatives with DNA in view of QSAR studies, Med. Chem. Res.,20, 1385–1393.

M. M. Mrugala (2013), Advances and challenges in the treatment of glioblastoma: a clinician’s perspective, Discov. Med.,15, 221–230.

M. W. Easson, F. R. Fronczek, T. J. Jensen and M. G. H. Vicente (2008), Synthesis and in vitro properties of trimethylamine- and phosphonate -substituted carboranylporphyrins for application in BNCT, Bioorg. Med. Chem.16, 3191–3208.

N. G. Oliveira, M. Castro, A. S. Rodrigues, I. C. Gonçalves, C. Martins, J. M. Toscano Rico and J. Rueff (2005), Effect of poly(ADP-ribosyl)ation inhibitors on the genotoxic effects of boron neutron capture reaction, Mutat. Res.,583, 36–48.

N. P. Barry and P. J. Sadler (2012), Dicarba-closo-dodecarboranecontaining half-sandwich complexes of ruthenium, osmium, rhodium and iridium: biological relevance and synthetic strategies, Chem. Soc. Rev.,41, 3264–3279.

P. Belmont and I. Dorange (2008), Acridine/acridone: a simple scaffold with a wide range of application in oncology, Expert Opin. Ther. Pat.,18, 1211–1224.

R. F. Barth (2009), Boron neutron capture therapy at the crossroads: challenges and opportunities, Appl. Radiat. Isot., 67, S3–S6.

R. F. Barth, A. H. Soloway and R. M. Brugger (1996), Boron neutron capture therapy of brain tumors: past history, current status, and future potential, Cancer Invest.,14, 534–550.

R. F. Barth, J. A. Coderre, M. G. Vicente and T. E. Blue (2005), Boron neutron capture therapy of cancer: current status and future prospects, Clin. Cancer Res.,11, 3987–4002.

R. Gahbauer, N. Gupta, T. Blue, J. Goodman, R. Barth, J. Grecula, A. H. Soloway, W. Sauerwein and A. Wambersie (1998), Boron neutron capture therapy: principles and potential, Recent Results Cancer Res.,150, 183–209.

R. J. Harrison, A. P. Reszka, S. M. Haider, B. Romagnoli, J. Morrell, M. A. Read, S. M. Gowan, C. M. Incles, L. R. Kelland and S. Neidle (2004), Evaluation of by disubstituted acridone derivatives as telomerase inhibitors: the importance of G-quadruplex binding, Bioorg. Med. Chem. Lett.,14, 5845–5849.

R. L. Moss (2014), Critical review, with an optimistic outlook, on Boron Neutron Capture Therapy (BNCT), Appl. Radiat. Isot.,88, 2–11.

R. P. Evstigneeva, A. V. Zaitsev, V. N. Luzgina, V. A. Ol’shevskaya and A. A. Shtil (2003), Carboranylporphyrins for boron neutron capture therapy of cancer, Curr. Med. Chem.: Anti-Cancer Agents,3, 383–392.

R. S. G. R. Seixas, A. M. S. Silva, D. C. G. A. Pinto and J. A. S. Cavaleiro (2008), A New Synthesis of Benzo[b]acridones, Synlett,3193–3197.

S. Altieri, S. Bortolussi, R. F. Barth, L. Roveda and A. Zonta (2009), Thirteenth International Congress on Neutron Capture Therapy, Appl. Radiat. Isot., 67, S1–S2.

S. Michel, T. Gaslonde and F. Tillequin (2004), Benzo[b]acronycine derivatives: a novel class of antitumor agents, Eur. J. Med. Chem.,39, 649–655.

S. Ronchi, D. Prosperi, C. Thimon, C. Morin and L. Panza (2005), Synthesis of mono- and bisglucuronylated carboranes, Tetrahedron: Asymmetry,16, 39–44.

T. Betzel, T. Heß, B. Waser, J. C. Reubi and F. Roesch (2008), Closo-Borane conjugated regulatory peptides retain high biological affinity: synthesis of closo-borane conjugated Tyr3-octreotate derivatives for BNCT, Bioconjugate Chem.,19, 1796–1802.

T. Kageji, Y. Mizobuchi, S. Nagahiro, Y. Nakagawan and H. Kumada (2011), Clinical results of boron neutron capture therapy (BNCT) for glioblastoma, Appl. Radiat. Isot.,69, 1823–1825.

T. Nguyen, G. L. Brownell, S. A. Holden, S. Kahl, M. Miura and B. A. Teicher (1993), Subcellular distribution of various boron compounds and implications for their efficacy in boron neutron capture therapy by Monte Carlo simulations, Radiat. Res.,133, 33–40.

T. Yamamoto, K. Nakai and A. Matsumura (2008), Boron neutron capture therapy for glioblastoma, Cancer Lett., 262, 143–152. tissue sarcoma of extremities: Candidate tumors for BNCT, Appl. Radiat. Isot.,88, 46–49. Organic & Biomolecular Chemistry Paper

W. Yang, R. F. Barth, G. Wu, T. Huo, W. Tjarks, M. Ciesielski, R. A. Fenstermaker, B. D. Ross, C. J. Wikstrand, K. J. Riley and P. J. Binns (2009), Convection enhanced delivery of boronated EGF as a molecular targeting agent for neutron capture therapy of brain tumors, J. Neurooncol.,95, 355–365.
How to Cite
Triatmoko, I., & Sutjipto, S. (2017). A Study of The Assessment for Boron Neutron Capture Therapy Agent. Indonesian Journal of Physics and Nuclear Applications, 2(1), 9-19. https://doi.org/10.24246/ijpna.v2i1.9-19