In Vivo Pharmacokinetics of a Boron Neutron Capture Agent in a Tumor-Bearing Rat Via Boron-11 MRS and MRI

Author(s):  
G. W. Kabalka ◽  
G. -Q. Cheng ◽  
C. Anderson ◽  
P. Bendel ◽  
P. Micca ◽  
...  
2021 ◽  
pp. 20210593
Author(s):  
Verónica A. Trivillin ◽  
Yanina V. Langle ◽  
Mónica A. Palmieri ◽  
Emiliano C.C. Pozzi ◽  
Silvia I. Thorp ◽  
...  

We previously demonstrated, for the first time, the abscopal effect of Boron Neutron Capture Therapy (BNCT) in an ectopic model of syngeneic colon cancer in BDIX rats. Objective: The aim of the present study was to evaluate the local and regional therapeutic efficacy and abscopal effect of BNCT mediated by boronophenyl-alanine, combined with Bacillus Calmette-Guerin (BCG) as an immunotherapy agent in this model. Methods: The local effect of treatment was evaluated in terms of tumor response in the irradiated tumor-bearing right hind flank. Metastatic spread to tumor-draining lymph nodes was analyzed as an indicator of regional effect. The abscopal effect of treatment was assessed as tumor growth inhibition in the contralateral (non-irradiated) left hind flank inoculated with tumor cells 2 weeks post-irradiation. The experimental groups BNCT, BNCT + BCG, BCG, Beam only (BO), BO +BCG, SHAM (tumor-bearing, no treatment, same manipulation) were studied. Results: BNCT and BNCT + BCG induced a highly significant local anti-tumor response, whereas BCG alone induced a weak local effect. BCG and BNCT + BCG induced a significant abscopal effect in the contralateral non-irradiated leg. The BNCT + BCG group showed significantly less metastatic spread to tumor-draining lymph nodes vs SHAM and vs BO. Conclusion: This study suggests that BNCT + BCG-immunotherapy would induce local, regional and abscopal effects in tumor-bearing animals. BNCT would be the main effector of the local anti-tumor effect whereas BCG would be the main effector of the abscopal effect. Advances in knowledge: Although the local effect of BNCT has been widely evidenced, this is the first study to show the local, regional and abscopal effects of BNCT combined with immunotherapy, contributing to comprehensive cancer treatment with combined therapies.


Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3609 ◽  
Author(s):  
Pulagam ◽  
Gona ◽  
Gómez-Vallejo ◽  
Meijer ◽  
Zilberfain ◽  
...  

Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]−) with hydrodynamic diameter of 37.8 ± 0.5 nm, core diameter of 19.2 ± 1.4 nm and ξ-potential of −18.0 ± 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4]− could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]−. Conclusions: PEG stabilized, COSAN-functionalised AuNPs could be synthesized, radiolabelled and evaluated in vivo using PET. The low tumour accumulation in the animal model assayed points to the need of tuning the size and geometry of the gold core for future studies.


2018 ◽  
Vol 35 (3) ◽  
pp. 213-216
Author(s):  
Atika Maysaroh ◽  
Kusminarto Kusminarto ◽  
Dwi Satya Palupi ◽  
Yohannes Sardjono

Cancer is one of the leading causes of death globally, with lung cancer being among the most prevalent. Boron Neutron Capture Therapy (BNCT) is a cancer therapy method that uses the interaction between thermal neutrons and boron-10 which produces a decaying boron-11 particle and emits alpha, lithium 7 and gamma particles. A study was carried out to model an in vivo experiment of rat organisms that have lung cancer. Dimensions of a rat’s body were used in Konijnenberg research. Modeling lung cancer type, non-small cell lung cancer, was used in Monte Carlo N Particle-X. Lung cancer was modeled with a spherical geometry consisting of 3 dimensions: PTV, GTV, and CTV. In this case, the neutron source was from the radial piercing beam port of Kartini Reactor, Yogyakarta. The variation of boron concentration was 20, 25, 30, 35, 40, and 40 µg/g cancer. The output of the MCNP calculation was neutron scattering dose, gamma-ray dose and neutron flux from the reactor. A neutron flux was used to calculate the alpha proton and gamma-ray dose from the interaction of tissue material and thermal neutrons. The total dose was calculated from a four-dose component in BNCT. The results showed that the dose rate will increase when the boron concentration is higher, whereas irradiating time will decrease.


2016 ◽  
Vol 1 (3) ◽  
pp. 151
Author(s):  
Agung Prastowo ◽  
Yohannes Sardjono ◽  
Widarto Widarto

A study of voxel mice model of MCNPX has been done for in vivo test Boron Neutron Capture Therapy (BNCT). Mathematical and parameters were used to construct the stylized Mice model phantom. The geometry was modified into simulation software MCNPX (Monte Carlo N-Particle eXtended) simulation input. The result of mice stylized model phantom has been showed Figure 3.


2016 ◽  
Vol 1 (2) ◽  
pp. 108
Author(s):  
Widarto Widarto ◽  
Isman Mulyadi Tri Atmoko ◽  
Gede Sutresna Wijaya

The quality manajement system program of in vitro / in vivo test facility of  Boron Neutron Capture Therapy (BNCT) methode as quality assurance requirement for utilization of radial pearcing beamport of Kartini research have been done.  Identification and management of technical specification and parameters meassurement of to the radial piercing beamport have been determined for preparing in vitro / in vivo test facility. The parameters are epithermal neutron flux is  9,8243E+05  n cm<sup>-2</sup> s<sup>-1</sup>and  thermal neutron flux is 3,0691E+06 n cm<sup>-2</sup> s<sup>-1</sup>, radiation shielding of parafin,  dimension and size  of piercing radial and instrumentatin and control system for automatic transfer of in vitro / in vivo samplels have been documented. Management system of the documents for fullfil  basic guidance to perform working job of in vitro / in vivo at the piercing radial beamport of Kartini Research Reactor in order purpose utilization of the reactor  for safety worker of the radiation area, society  and invironment beeing safely


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