Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas

Object. To improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, the authors used epithermal rather than thermal neutrons for deep penetration and two boron compounds—sodium borocaptate (BSH) and boronophenylalanine (BPA)—with different accumulation mechanisms to increase the boron level in tumors while compensating for each other's faults. Methods. Thirteen patients, 10 of whom harbored a glioblastoma multiforme (GBM), one a gliosarcoma, one an anaplastic astrocytoma, and one an anaplastic oligoastrocytoma, were treated using this modified BNCT between January 2002 and December 2003. Postoperatively, neuroimaging revealed that only one patient with a GBM had no lesion enhancement postoperatively. The patients underwent 18F-BPA positron emission tomography, if available, to assess the accumulation and distribution of BPA before neutron radiotherapy. The neutron fluence rate was estimated using the Simulation Environments for Radiotherapy Applications dose-planning system before irradiation. The patients' volume assessments were performed using magnetic resonance (MR) imaging or computerized tomography (CT) scanning. Improvements in the disease as seen on neuroimages were assessed between 2 and 7 days after irradiation to determine the initial effects of BNCT; its maximal effects were also analyzed on serial neuroimages. The mean tumor volume before BNCT was 42.3 cm3. Regardless of the pre-BNCT tumor volume, in every patient harboring an assessable lesion, improvements on MR or CT images were recognized both at the initial assessment (range of volume reduction rate 17.4–71%, mean rate 46.4%) and at follow-up assessments (range of volume reduction rates 30.3–87.6%, mean rate 58.5%). More than 50% of the contrast-enhanced lesions disappeared in eight of the 12 patients during the follow-up period. Conclusions. This modified BNCT produced a good improvement in malignant gliomas, as seen on neuroimages.

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Boron neutron capture therapy for malignant gliomas

Annals of Medicine ◽

10.3109/07853890008995913 ◽

2000 ◽

Vol 32 (1) ◽

pp. 81-85 ◽

Cited By ~ 39

Author(s):

Aidnag Z Diaz ◽

Jeffrey A Coderre ◽

Arjun D Chanana ◽

Ruimei Ma

Keyword(s):

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Malignant Gliomas ◽

Neutron Capture Therapy ◽

Boron Neutron Capture

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Boron neutron capture therapy for recurrent malignant meningioma

Journal of Neurosurgery ◽

10.3171/jns.2006.105.6.898 ◽

2006 ◽

Vol 105 (6) ◽

pp. 898-903 ◽

Cited By ~ 19

Author(s):

Yoji Tamura ◽

Shin-Ichi Miyatake ◽

Naosuke Nonoguchi ◽

Shirou Miyata ◽

Kunio Yokoyama ◽

...

Keyword(s):

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Malignant Gliomas ◽

Contralateral Side ◽

Neutron Capture Therapy ◽

Malignant Meningioma ◽

Boron Neutron Capture ◽

First Case ◽

Second Resection ◽

Promising Treatment

✓ Malignant meningioma is a rare brain tumor with a high risk of recurrence. If this tumor recurs after complete resection and adjuvant radiotherapy, there is no optimal treatment to control it. The authors report the first case of recurrent malignant meningioma treated using boron neutron capture therapy (BNCT). This 25-year-old pregnant woman presented with a large frontal tumor. After her baby was born, she underwent gross-total resection of the tumor. A second resection and three Gamma Knife surgeries could not control progression of the enhancing mass; therefore, the authors applied BNCT based on their experience with it in the treatment of malignant gliomas. The minimum tumor dose and maximum brain tissue dose were estimated as 39.7 Gy-Eq and less than 9.0 Gy-Eq, respectively. Before BNCT the patient was mobile by wheelchair only, whereas 1 week after therapy she was able to walk. Twenty-two weeks later she underwent a second BNCT for tumor regrowth on the contralateral side, and the lesion was subsequently reduced. The tumor volume was markedly decreased from 65.6 cm3 at the time of the first BNCT to 31.8 cm3 at 26 weeks thereafter. The treatment of recurrent malignant meningioma is difficult and has been discouraging thus far. Data in the present case indicate that BNCT may be a promising treatment option for this challenging tumor.

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Homocystamide Conjugates of Human Serum Albumin as a Platform to Prepare Bimodal Multidrug Delivery Systems for Boron Neutron Capture Therapy

Molecules ◽

10.3390/molecules26216537 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6537

Author(s):

Tatyana Popova ◽

Maya A. Dymova ◽

Ludmila S. Koroleva ◽

Olga D. Zakharova ◽

Vladimir A. Lisitskiy ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Malignant Gliomas ◽

Neutron Capture Therapy ◽

Human Glioma ◽

Boron Compounds ◽

Boron Neutron Capture

Boron neutron capture therapy is a unique form of adjuvant cancer therapy for various malignancies including malignant gliomas. The conjugation of boron compounds and human serum albumin (HSA)—a carrier protein with a long plasma half-life—is expected to extend systemic circulation of the boron compounds and increase their accumulation in human glioma cells. We report on the synthesis of fluorophore-labeled homocystamide conjugates of human serum albumin and their use in thiol-‘click’ chemistry to prepare novel multimodal boronated albumin-based theranostic agents, which could be accumulated in tumor cells. The novelty of this work involves the development of the synthesis methodology of albumin conjugates for the imaging-guided boron neutron capture therapy combination. Herein, we suggest using thenoyltrifluoroacetone as a part of an anticancer theranostic construct: approximately 5.4 molecules of thenoyltrifluoroacetone were bound to each albumin. Along with its beneficial properties as a chemotherapeutic agent, thenoyltrifluoroacetone is a promising magnetic resonance imaging agent. The conjugation of bimodal HSA with undecahydro-closo-dodecaborate only slightly reduced human glioma cell line viability in the absence of irradiation (~30 μM of boronated albumin) but allowed for neutron capture and decreased tumor cell survival under epithermal neutron flux. The simultaneous presence of undecahydro-closo-dodecaborate and labeled amino acid residues (fluorophore dye and fluorine atoms) in the obtained HSA conjugate makes it a promising candidate for the combination imaging-guided boron neutron capture therapy.

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