Abstract
This short review summarizes the issue of boron distribution monitoring in boron neutron capture therapy (BNCT), which remains a serious drawback of this powerful oncological treatment. Here we present the monitoring methods that are presently used with particular emphasis on the positron emission tomography (PET) which has the highest potential to be used for the real-time monitoring of boron biodistribution. We discuss the possibility of using present PET scanners to determine the boron uptake in vivo before the BNCT treatment with the use of p-boronphenylalanine (BPA) labeled with 18F isotope. Several examples of preclinical studies and clinical trials performed with the use of [18F]FBPA are shown. We also discuss shortly the perspectives of using other radiotracers and boron carriers which may significantly improve the boron imaging with the use of the state-of-the-art Total-Body PET scanners providing a theranostic approach in the BNCT.
Funding source: SciMat Priority Research Area under the Strategic Programme Excellence Initiative at the Jagielloni-an University
Award Identifier / Grant number: U1U/P05/NO/03.47 U1U/P05/NW/03.23
Funding source: Polish National Centre for Research and Development
Award Identifier / Grant number: LIDER/17/0046/L-7/15/NCBR/2016
Funding source: Priority Research Area DigiWorld under the program Excellence Initiative-Research University at the Jagiellonian University
Research funding: This work has been supported by Grants U1U/P05/NW/03.23 and U1U/P05/NO/03.47 from the SciMat Priority Research Area under the Strategic Programme Excellence Initiative at the Jagiellonian University. We acknowledge the support from the Polish National Centre for Research and Development through Grant No. LIDER/17/0046/L-7/15/NCBR/2016 and from the Priority Research Area DigiWorld under the program Excellence Initiative-Research University at the Jagiellonian University in Kraków. The founding organizations played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Not applicable.
Ethical approval: Not applicable.
References
1. Japanese Society of Neutron Capture Therapy. What is BNCT? [Online]. Available from: http://www.jsnct.jp/e/about_nct/gen.html [Accessed 24 Aug 2021].Search in Google Scholar
2. Sauerwein, WAG. Principles and roots of neutron capture therapy. In: Sauerwein, WAG, Wittig, A, Moss, R, Nakagawa, Y, editors. Neutron capture therapy: principles and applications. Berlin Heidelberg: Springer-Verlag; 2012.10.1007/978-3-642-31334-9_1Search in Google Scholar PubMed
3. Nedunchezhian, K, Aswath, N, Thiruppathy, M, Thirugnanamurthy, S. Boron neutron capture therapy-A literature review. J Clin Diagn Res 2016;10:ZE01–4. https://doi.org/10.7860/JCDR/2016/19890.9024.Search in Google Scholar
4. Enger, SA, Giusti, V, Fortin, M-A, Lundqvist, H, Rosenschöld, PM. Dosimetry for gadolinium neutron capture therapy (GdNCT). Radiat Meas 2013;59:233–40. https://doi.org/10.1016/j.radmeas.2013.05.009.Search in Google Scholar
5. Gibson, CR, Staubus, AE, Barth, RE, Yang, W, Ferkefich, AK, Moeschberger, MM. Pharmacokinetics of sodium borocaptate: a critical assessment of dosing paradigms for boron neutron capture therapy. J Neuro Oncol 2003;62:157–69. https://doi.org/10.1007/bf02699942.Search in Google Scholar
6. Michiue, H, Sakurai, Y, Kondo, N, Kitamatsu, M, Bin, F, Nakajima, K, et al.. The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide. Biomaterials 2014;35:3396–405. https://doi.org/10.1016/j.biomaterials.2013.12.055.Search in Google Scholar
7. Stella Pharma Corporation. News release: STELLA PHARMA will launch Steboronine®, the World’s first BNCT drug, on May 20; 2020. Available from: https://stella-pharma.co.jp/cp-bin/wordpress5/wp-content/uploads/2020/05/Steboronine-launched_ENG.pdf [Accessed 25 Aug 2021].Search in Google Scholar
8. Nakamura, H, Kirihata, M. Boron compounds: new candidates for boron carriers in BNCT, principles and roots of neutron capture therapy. In: Sauerwein, WAG, Wittig, A, Moss, R, Nakagawa, Y, editors. Neutron capture therapy: principles and applications. Berlin Heidelberg: Springer-Verlag Berlin Heidelberg; 2012.10.1007/978-3-642-31334-9_7Search in Google Scholar
9. Taskaev, S, Berendeev, E, Bikchurina, M, Bykov, T, Kasatov, D, Kolesnikov, I, et al.. Neutron source based on vacuum insulated tandem accelerator and lithium target. Biology 2021;10:350. https://doi.org/10.3390/biology10050350.Search in Google Scholar
10. Kreiner, AJ. Accelerator-based BNCT. In: Sauerwein, WAG, Wittig, A, Moss, R, Nakagawa, Y, editors. Neutron capture therapy: principles and applications. Berlin Heidelberg: Springer-Verlag; 2012.10.1007/978-3-642-31334-9_3Search in Google Scholar
11. Wittig, A, Sauerwein, WAG. Boron analysis and boron imaging in BNCT. In: Sauerwein, WAG, Wittig, A, Moss, R, Nakagawa, Y, editors. Neutron capture therapy: principles and applications. Berlin Heidelberg: Springer-Verlag; 2012.10.1007/978-3-642-31334-9_9Search in Google Scholar
12. Bendel, P, Sauerwein, W. Optimal detection of the neutron capture therapy agent borocaptate sodium (BSH): a comparison between 1H and 10B NMR. Med Phys 2001;28:178. https://doi.org/10.1118/1.1339227.Search in Google Scholar
13. Timonen, M, Kankaanranta, L, Lundbom, N, Collan, J, Kangasmaki, A, Kortesniemi, M, et al.. 1H MRS studies in the Finnish boron neutron capture therapy project: detection of 10B-carrier, L-p-boronophenylalanine-fructose. Eur J Radiol 2005;56:154–9. https://doi.org/10.1016/j.ejrad.2005.03.017.Search in Google Scholar
14. Porcari, P, Capuani, S, D’Amore, E, Lecce, M, La Bella, A, Fasano, F, et al.. In vivo 19F MR imaging and spectroscopy for the BNCT optimization. Appl Radiat Isot 2009;67:S365–8. https://doi.org/10.1016/j.apradiso.2009.03.065.Search in Google Scholar
15. Icten, O, Ali Kose, D, Matissek, SJ, Misurelli, JA, Elsawa, SF, Hosmane, NS, et al.. Gadolinium borate and iron oxide bioconjugates: nanocomposites of next generation with multifunctional applications. Mater Sci Eng C 2018;92:317–28. https://doi.org/10.1016/j.msec.2018.06.042.Search in Google Scholar
16. Alberti, D, Protti, N, Toppino, A, Deagostino, A, Lanzardo, S, Bortolussi, S, et al.. A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment. Nanomed Nanotechnol Biol Med 2015;11:741–50. https://doi.org/10.1016/j.nano.2014.12.004.Search in Google Scholar
17. Sauerwein, WAG, Sancey, L, Hey-Hawkins, E, Kellert, M, Panza, L, Imperio, D, et al.. Theranostics in boron neutron capture therapy. Life 2021;11:330. https://doi.org/10.3390/life11040330.Search in Google Scholar
18. Valda, A, Minsky, DM, Kreiner, AJ, Burlon, AA, Somacal, H. Development of a tomographic system for online dose measurements in BNCT (boron neutron capture therapy). Braz J Phys 2005;35:785. https://doi.org/10.1590/s0103-97332005000500017.Search in Google Scholar
19. Manabe, M, Nakamura, S, Murata, I. Study on measuring device arrangement of array-type CdTe detector for BNCT-SPECT. Rep Radiother Oncol 2016;21:102–7. https://doi.org/10.1016/j.rpor.2015.04.002.Search in Google Scholar
20. Gong, C, Tang, X, Fatemi, S, Yu, H, Shao, W, Shu, D, et al.. A Monte Carlo study of SPECT in boron neutron capture therapy for a heterogeneous human phantom. Int J Radiat Res 2018;16:33–43.Search in Google Scholar
21. Glaudemans, AW, Enting, RH, Heesters, MA, Dierckx, RA, van Rheenen, RW, Walenkamp, AM, et al.. Value of 11C-methionine PET in imaging brain tumours and metastases. Eur J Nucl Med Mol Imag 2013;40:615–35. https://doi.org/10.1007/s00259-012-2295-5.Search in Google Scholar
22. Sharma, R, D’Souza, M, Jaimini, A, Hazari, PP, Saw, S, Pandey, S, et al.. A comparison study of (11)C-methionine and (18)F-fluorodeoxyglucose positron emission tomography-computed tomography scans in evaluation of patients with recurrent brain tumors. Indian J Nucl Med 2016;31:93–102. https://doi.org/10.4103/0972-3919.178254.Search in Google Scholar
23. Alavi, A, Hess, S, Werner, TJ, Høilund-Carlsen, PF. An update on the unparalleled impact of FDG-PET imaging on the day-to-day practice of medicine with emphasis on management of infectious/inflammatory disorders. Eur J Nucl Med Mol Imag 2020;47:18–27. https://doi.org/10.1007/s00259-019-04490-6.Search in Google Scholar
24. Ishiwata, K, Ido, T, Mejia, AA, Ichihashi, M, Mishima, Y. Synthesis and radiation dosimetry of 4-borono-2-[18F]fluoro-D,Lphenylalanine: a target compound for PET and boron neutron capture therapy. Int J Radiat Appl Instrum A 1991;42:325–8. https://doi.org/10.1016/0883-2889(91)90133-l.Search in Google Scholar
25. Ishiwata, K. 4-Borono-2-18F-fluoro-l-phenylalanine PET for boron neutron capture therapy-oriented diagnosis: overview of a quarter century of research. Ann Nucl Med 2019;33:223–36. https://doi.org/10.1007/s12149-019-01347-8.Search in Google Scholar
26. Ishiwata, K, Ido, T, Kawamura, M, Kubota, K, Ichihashi, M, Mishima, Y. 4-Borono-2-[18F]fluoro-d,l-phenylalanine as a target compound for boron neutron capture therapy: tumor imaging potential with positron emission tomography. Nucl Med Biol 1991;18:745–51. https://doi.org/10.1016/0883-2897(91)90013-b.Search in Google Scholar
27. Coderre, JA, Glass, JD, Fairchild, RG, Roy, U, Cohen, S, Fand, I. Selective targeting of boronophenylalanine to melanoma in BALB/c mice for neutron capture therapy. Cancer Res 1987;47:6377–83.Search in Google Scholar
28. Ishiwata, K, Ido, T, Honda, C, Kawamura, M, Ichihashi, M, Mishima, Y. 4-Borono-2-[18F]fluoro-d,l-phenylalanine: a possible tracer for melanoma diagnosis with PET. Nucl Med Biol 1992;19:311–8. https://doi.org/10.1016/0883-2897(92)90116-g.Search in Google Scholar
29. Wang, HE, Liao, AH, Deng, WP, Chang, PF, Chen, JC, Chen, FD, et al.. Evaluation of 4-borono-2-18F-fluoro-l-phenylalaninefructose as a probe for boron neutron capture therapy in a glioma bearing rat model. J Nucl Med 2004;45:302–8.Search in Google Scholar
30. Evangelista, L, Jori, G, Martini, D, Sotti, G. Boron neutron capture therapy and 18F-labelled borophenylalanine positron emission tomography: a critical and clinical overview of the literature. Appl Radiat Isot 2013;74:9–101. https://doi.org/10.1016/j.apradiso.2013.01.001.Search in Google Scholar
31. Aihara, T, Hiratsuka, J, Morita, N, Uno, M, Sakurai, Y, Maruhashi, A, et al.. First clinical case of boron neutron capture therapy for head and neck malignancies using 18F-BPA PET. Case Rep 2006;28:850–5. https://doi.org/10.1002/hed.20418.Search in Google Scholar
32. Kabalka, GW, Nichols, TL, Smith, GT, Miller, LF, Khan, MK, Busse, PM. The use of positron emission tomography to develop boron neutron capture therapy treatment plans for metastatic malignant melanoma. J Neurooncol 2003;62:187–95. https://doi.org/10.1007/bf02699944.Search in Google Scholar
33. Iguchi, Y, Michiue, H, Kitamatsu, M, Hayashi, Y, Takenaka, F, Nishiki, T, et al.. Tumor-specific delivery of BSH-3R for boron neutron capture therapy and positron emission tomography imaging in a mouse brain tumor model. Biomaterials 2015;56:10–7. https://doi.org/10.1016/j.biomaterials.2015.03.061.Search in Google Scholar
34. Moskal, P, Stępień, EŁ. Prospects and clinical perspectives of total-body PET imaging using plastic scintillators. Pet Clin 2020;15:439–45. https://doi.org/10.1016/j.cpet.2020.06.009.Search in Google Scholar
35. Vandenberghe, S, Moskal, P, Karp, JS. State of the art in total body PET. EJNMMI Phys 2020;7:35. https://doi.org/10.1186/s40658-020-00290-2.Search in Google Scholar
36. Cherry, S, Karp, J, Moses, W, Qi, J, Bec, J, Berg, E, et al.. EXPLORER: an ultra-sensitive total-body PET scanner for biomedical research. In: Proceedings of IEEE nuclear science symposium and medical imaging conference; 2013:M03–01 pp.Search in Google Scholar
37. Badawi, RD, Shi, H, Hu, P, Chen, S, Xu, T, Price, PM, et al.. First human imaging studies with the EXPLORER total-body PET scanner. J Nucl Med 2019;60:299–303. https://doi.org/10.2967/jnumed.119.226498.Search in Google Scholar
38. Moskal, P, Salabura, P, Silarski, M, Smyrski, J, Zdebik, J, Zieliński, M. Novel detector systems for the positron emission tomography. Bio-Algorithms Med-Syst. 2011;7:73–8.Search in Google Scholar
39. Moskal, P, Niedźwiecki, Sz, Bednarski, T, Czerwiński, E, Kapłon, Ł, Kubicz, E, et al.. Test of a single module of the J-PET scanner based on plastic scintillators. Nucl Instrum Methods Phys Res A 2014;764:317–21. https://doi.org/10.1016/j.nima.2014.07.052.Search in Google Scholar
40. Moskal, P, Zoń, N, Bednarski, T, Białas, P, Czerwiński, E, Gajos, A, et al.. A novel method for the line-of-response and time-of-flight reconstruction in TOF-PET detectors based on a library of synchronized model signals. Nucl Instrum Methods A 2015;775:54–62. https://doi.org/10.1016/j.nima.2014.12.005.Search in Google Scholar
41. Kapłon, Ł. Technical attenuation length Measurement of plastic scintillator strips for the total-body J-PET scanner. IEEE Trans Nucl Sci 2020;67:2286–9. https://doi.org/10.1109/tns.2020.3012043.Search in Google Scholar
42. Kapłon, Ł, Moskal, G. Blue-emitting polystyrene scintillators for plastic scintillation dosimetry. Bio-Algorithms Med-Syst 2021;17:191–7.10.1515/bams-2021-0088Search in Google Scholar
43. Moskal, P, Rundel, O, Alfs, D, Bednarski, T, Białas, P, Czerwiński, E, et al.. Time resolution of the plastic scintillator strips with matrix photomultiplier readout for J-PET tomograph. Phys Med Biol 2016;61:2025. https://doi.org/10.1088/0031-9155/61/5/2025.Search in Google Scholar
44. Wieczorek, A, Dulski, K, Niedźwiecki, Sz, Alfs, D, Białas, P, Curceanu, C, et al.. Novel scintillating material 2-(4-styrylphenyl)benzoxazole for the fully digital and MRI compatible J-PET tomograph based on plastic scintillators. PLoS ONE 2017;12:e0186728. https://doi.org/10.1371/journal.pone.0186728.Search in Google Scholar
45. Moskal, P, Kowalski, P, Shopa, RY, Raczyński, L, Baran, J, Chug, N, et al.. Simulating NEMA characteristics of the modular total-body J-PET scanner—an economic total-body PET from plastic scintillators. Phys Med Biol 2021;66:175015. https://doi.org/10.1088/1361-6560/ac16bd.Search in Google Scholar
46. Raczyński, L, Wiślicki, W, Klimaszewski, K, Krzemień, W, Kopka, P, Kowalski, P, et al.. 3D TOF-PET image reconstruction using total variation regularization. Phys Med 2020;80:230–42. https://doi.org/10.1016/j.ejmp.2020.10.011.Search in Google Scholar
47. Shopa, RY, Klimaszewski, K, Kopka, P, Kowalski, P, Krzemień, W, Raczyński, L, et al.. Optimisation of the event-based TOF filtered back-projection for online imaging in total-body. J-PET Med Image Anal 2021;73:102199. https://doi.org/10.1016/j.media.2021.102199.Search in Google Scholar
48. Pałka, M, Strzempek, P, Korcyl, G, Bednarski, T, Niedźwiecki, Sz, Białas, P, et al.. Multichannel FPGA based MVT system for high precision time (20 ps RMS) and charge measurement. J Instrum 2017;12:P08001.10.1088/1748-0221/12/08/P08001Search in Google Scholar
49. Korcyl, G, Białas, P, Curceanu, C, Czerwiński, E, Dulski, K, Flak, B, et al.. Evaluation of single-chip, real-time tomographic data processing on FPGA SoC devices. IEEE Trans Med Imag 2018;37:2526–35. https://doi.org/10.1109/tmi.2018.2837741.Search in Google Scholar
50. Moskal, P. A hybrid TOF-PET/CT tomograph. European patent EP 3039456, 2019.Search in Google Scholar
51. Moskal, P. Hybrid TOF-PET/MRI tomograph. United States patent US 10,520,568, 2019.Search in Google Scholar
52. Moskal, P, Gajos, A, Mohammed, M, Chhokar, J, Chug, N, Curceanu, C, et al.. Testing CPT symmetry in ortho-positronium decays with positronium annihilation tomography. Nat Commun 2021;12:5658. https://doi.org/10.1038/s41467-021-25905-9.Search in Google Scholar
53. Moskal, P, Dulski, K, Chug, N, Curceanu, C, Czerwiński, E, Dadgar, M, et al.. Positronium imaging with the novel multiphoton PET scanner. Sci Adv 2021;7:eabh4394. https://doi.org/10.1126/sciadv.abh4394.Search in Google Scholar
54. Moskal, P, Kisielewska, D, Bura, Z, Chhokar, C, Curceanu, C, Czerwiński, E, et al.. Performance assessment of the 2γ positronium imaging with the total-body PET scanners. EJNMMI Phys 2021;7:44. https://doi.org/10.1186/s40658-020-00307-w.Search in Google Scholar
55. Moskal, P, Kisielewska, D, Curceanu, C, Czerwiński, E, Dulski, K, Gajos, A, et al.. Feasibility study of the positronium imaging with the J-PET tomograph. Phys Med Biol 2019;64:055017. https://doi.org/10.1088/1361-6560/aafe20.Search in Google Scholar
56. Moskal, P, Jasińska, B, Stępień, EŁ, Bass, SD. Positronium in medicine and biology. Nature Rev Phys 2019;1:527–9. https://doi.org/10.1038/s42254-019-0078-7.Search in Google Scholar
57. Sitarz, M, Cussonneau, J-P, Matulewicz, T, Haddad, F. Radionuclide candidates for β+γ coincidence PET: an overview. Appl Radiat Isot 2020;155:108898. https://doi.org/10.1016/j.apradiso.2019.108898.Search in Google Scholar
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- New trends in theranostics
- Reviews
- Unparalleled and revolutionary impact of PET imaging on research and day to day practice of medicine
- Research Articles
- Theranostics – present and future
- Peptide receptor radionuclide therapy as a tool for the treatment of severe hypoglycemia in patients with primary inoperable insulinoma
- History of radiotherapy in Poland. A brief outline of the problem
- Reviews
- Radioactive nuclei for β+γ PET and theranostics: selected candidates
- Prospects for the production of radioisotopes and radiobioconjugates for theranostics
- History of positron emission tomography (PET) in Poland
- Progress and perspectives in total body PET systems instrumentation
- Perspectives of brain imaging with PET systems
- Combined BNCT and PET for theranostics
- Novel biomarker and drug delivery systems for theranostics – extracellular vesicles
- Positronium as a biomarker of hypoxia
Articles in the same Issue
- Frontmatter
- Editorial
- New trends in theranostics
- Reviews
- Unparalleled and revolutionary impact of PET imaging on research and day to day practice of medicine
- Research Articles
- Theranostics – present and future
- Peptide receptor radionuclide therapy as a tool for the treatment of severe hypoglycemia in patients with primary inoperable insulinoma
- History of radiotherapy in Poland. A brief outline of the problem
- Reviews
- Radioactive nuclei for β+γ PET and theranostics: selected candidates
- Prospects for the production of radioisotopes and radiobioconjugates for theranostics
- History of positron emission tomography (PET) in Poland
- Progress and perspectives in total body PET systems instrumentation
- Perspectives of brain imaging with PET systems
- Combined BNCT and PET for theranostics
- Novel biomarker and drug delivery systems for theranostics – extracellular vesicles
- Positronium as a biomarker of hypoxia