Measured microdosimetric spectra and therapeutic potential of boron neutron capture enhancement of 252Cf brachytherapy

Californium-252 is a neutron-emitting radioisotope used as a brachytherapy source for radioresistant tumors. Presented here are microdosimetric spectra measured as a function of simulated site diameter and distance from applicator tube 252Cf sources. These spectra were measured using miniature tissue-equivalent proportional counters (TEPCs). An investigation of the clinical potential of boron neutron capture (BNC) enhancement of 252Cf brachytherapy is also provided. The absorbed dose from the BNC reaction was measured using a boron-loaded miniature TEPC. Measured neutron, photon and BNC absorbed dose components are provided as a function of distance from the source. In general, the absorbed dose results show good agreement with results from other measurement techniques. A concomitant boost to 252Cf brachytherapy may be provided through the use of the BNC reaction. The potential magnitude of this BNC enhancement increases with increasing distance from the source and is capable of providing a therapeutic gain greater than 30% at a distance of 5 cm from the source, assuming currently achievable boron concentrations.     

Calculation of dose components in head phantom for boron neutron capture therapy.

Application of neutrons to cancer treatment has been a subject of considerable clinical and research interest since the discovery of the neutron by Chadwick in 1932 (3). Boron neutron capture therapy (BNCT) is a technique of radiation oncology which is used in treating brain cancer (glioblastoma multiform) or melanoma and that consists of preferentially loading a compound containing 10B into the tumor location, followed by the irradiation of the patient with a beam of neutron. Dose distribution for BNCT is mainly based on Monte Carlo simulations. In this work, the absorbed dose spatial distribution resultant from an idealized neutron beam incident upon ahead phantom is investigated using the Monte Carlo N-particles code, MCNP 4B. The phantom model used is based on the geometry of a circular cylinder on which sits an elliptical cylinder capped by half an ellipsoid representing the neck and head, both filled with tissue-equivalent material. The neutron flux and the contribution of individual absorbed dose components, as a function of depths and of radial distance from the beam axis (dose profiles) in phantom model, is presented and discussed. For the studied beam the maximum thermal neutron flux is at a depth of 2 cm and the maximum gamma dose at a depth of 4 cm.     

Tissue composition effect on dose distribution in neutron brachytherapy/neutron capture therapy

Aim

The aim of this study is to assess the effect of the compositions of various soft tissues and tissue-equivalent materials on dose distribution in neutron brachytherapy/neutron capture therapy.

Background

Neutron brachytherapy and neutron capture therapy are two common radiotherapy modalities.

Materials and methods

Dose distributions were calculated around a low dose rate ²⁵²Cf source located in a spherical phantom with radius of 20.0 cm using the MCNPX code for seven soft tissues and three tissue-equivalent materials. Relative total dose rate, relative neutron dose rate, total dose rate, and neutron dose rate were calculated for each material. These values were determined at various radial distances ranging from 0.3 to 15.0 cm from the source.

Results

Among the soft tissues and tissue-equivalent materials studied, adipose tissue and plexiglass demonstrated the greatest differences for total dose rate compared to 9-component soft tissue. The difference in dose rate with respect to 9-component soft tissue varied with compositions of the materials and the radial distance from the source. Furthermore, the total dose rate in water was different from that in 9-component soft tissue.

Conclusion

Taking the same composition for various soft tissues and tissue-equivalent media can lead to error in treatment planning in neutron brachytherapy/neutron capture therapy. Since the International Commission on Radiation Units and Measurements (ICRU) recommends that the total dosimetric uncertainty in dose delivery in radiotherapy should be within ±5%, the compositions of various soft tissues and tissue-equivalent materials should be considered in dose calculation and treatment planning in neutron brachytherapy/neutron capture therapy.     

Microdosimetry for boron neutron capture therapy.

Preclinical studies for boron neutron capture therapy (BNCT) using epithermal neutrons are ongoing at several laboratories. The absorbed dose in tumor cells is a function of the thermal neutron flux at depth, the microscopic boron concentration, and the size of the cell. Dosimetry is therefore complicated by the admixture of thermal, epithermal, and fast neutrons, plus gamma rays, and the array of secondary high-linear-energy-transfer particles produced within the patient from neutron interactions. Microdosimetry can be a viable technique for determining absorbed dose and radiation quality. A 2.5-cm-diameter tissue-equivalent gas proportional counter has been built with 50 parts per million (ppm) 10B incorporated into the walls and counting gas to simulate the boron uptake anticipated in tumors. Measurements of lineal energy (y) spectra for BNCT in simulated volumes of 1-10 microns diameter show a dose enhancement factor of 4.3 for 30 ppm boron, and a "y" of 250 keV/microns for the boron capture process. Chamber design plus details of experimental and calculated linear energy spectra will be presented.     

A Monte Carlo investigation of the dosimetric properties of monoenergetic neutron beams for neutron capture therapy

A Monte Carlo simulation study has been carried out to investigate the suitability of neutron beams of various energies for therapeutic efficacy in boron neutron capture therapy. The dosimetric properties of unidirectional, monoenergetic neutron beams of varying diameters in two different phantoms (a right-circular cylinder and an ellipsoid) made of brain-equivalent material were examined. The source diameter was varied from 0.0 to 20.0 cm; neutron energies ranged from 0.025 eV up to 800 keV, the maximum neutron energy generated by a tandem cascade accelerator using 2.5-MeV protons in a 7Li(p,n)7Be reaction. Such a device is currently under investigation for use as a neutron source for boron neutron capture therapy. The simulation studies indicate that the maximum effective treatment depth (advantage depth) in the brain is 10.0 cm and is obtainable with a 10-keV neutron beam. A useful range of energies, defined as those neutron energies capable of effectively treating to a depth of 7 cm in brain tissue, is found to be 4.0 eV to 40.0 keV. Beam size is shown not to affect advantage depth as long as the entire phantom volume is used in determining this depth. Dose distribution in directions parallel to and perpendicular to the beam direction are shown to illustrate this phenomenon graphically as well as to illustrate the differences in advantage depth and advantage ratio and the contribution of individual dose components to tumor dose caused by the geometric differences in phantom shape.     

Detailed analysis of dose difference in using water as tissue-equivalent material in 252Cf brachytherapy

AimThe purpose of this study is to analyse how small variations in the elemental composition of soft tissue lead to differences in dose distributions from a ²⁵²Cf brachytherapy source and to determine the error percentage in using water as a tissue-equivalent material.BackgroundWater is normally used as a tissue-equivalent phantom material in radiotherapy dosimetry.Materials and methodsNeutron energy spectra, neutron and gamma-ray dose rate distributions were calculated for a ²⁵²Cf AT source located at the center of a spherical phantom filled with various types of tissue compositions: adipose, brain, muscle, International Commission on Radiation Units and Measurements (ICRU) report No. 44 9-component soft tissue and water, using Monte Carlo simulation.ResultsThe obtained results showed differences between total dose rates in various tissues relative to water varying between zero and 4.94%. The contributions of neutron and total gamma ray doses to these differences are, on average, 81% and 19%, respectively. It was found that the dose differences between various soft tissues and water depend not only on the soft tissue composition, but also on the beam type emitted from the ²⁵²Cf source and the distance from the source.ConclusionAssuming water as a tissue-equivalent material, although leads to overestimation of dose rate (except in the case of adipose tissue), is acceptable and suitable for use in ²⁵²Cf brachytherapy treatment planning systems based on the recommendation by the ICRU that the uncertainties in dose delivery in radiotherapy should be lower than 5%.     

Boron neutron capture therapy of a murine melanoma with p-boronophenylalanine: dose-response analysis using a morbidity index

Boron-10 concentrations of 20 or 40 micrograms/g were attained in mouse B16 melanomas following one or two intragastric doses of p-boronophenylalanine (750 mg/kg body weight per dose), respectively. Tumor-to-normal-tissue (blood, muscle) boron concentration ratios were 4:1-6:1. The efficacy of boron neutron capture irradiation was monitored using the Wilcoxon two-sample test in conjunction with a system of ranking outcomes of different therapies that compared living mice and mice sacrificed because of excessive tumor growth concomitantly. Median survivals were extended progressively as radiation doses were increased up to 38.7 gray-equivalent (gray X relative biological effectiveness), with one of five and one of six tumors cured in each of the two highest dose groups, respectively. When comparable tumor inhibitory doses of 250-kVp X rays were used to treat these tumors, instead of the transient erythema and edema that resulted from boron neutron capture therapy, there resulted irreversible muscle necrosis in the irradiated zone and atrophy of the foot distal to the irradiated zone. The improvement in treatment outcome with boron neutron capture therapy is attributable to unprecedented tumor-to-normal-tissue radiation dose ratios of approximately 2.8 to 3.6.     

Physical,dosimetric and clinical aspects and delivery systems in neutron capture therapy

Neutron capture therapy (NCT) is a targeted radiotherapy for cancer treatment. In this method, neutrons with a spectra/specific energy (depending on the type of agent used for NCT) are captured with an agent that has a high cross-section with these neutrons. There are some agents that have been proposed in NCT including ¹⁰B, ¹⁵⁷Gd and ³³S. Among these agents, only ¹⁰B is used in clinical trials. Application of ¹⁵⁷Gd is limited to in-vivo and in-vitro research. In addition, ³³S has been applied in the field of Monte Carlo simulation. In BNCT, the only two delivery agents which are presently applied in clinical trials are BPA and BSH, but other delivery systems are being developed for more effective treatment in NCT. Neutron sources used in NCT are fission reactors, accelerators, and ²⁵²Cf. Among these, fission reactors have the most application in NCT. So far, BNCT has been applied to treat various cancers including glioblastoma multiforme, malignant glioma, malignant meningioma, liver, head and neck, lung, colon, melanoma, thyroid, hepatic, gastrointestinal cancer, and extra-mammary Paget's disease. This paper aims to review physical, dosimetric and clinical aspects as well as delivery systems in NCT for various agents.     

A radiobiological model for the relative biological effectiveness of high-dose-rate 252Cf brachytherapy

While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.     

On the eptihermal neutron energy limit for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT): Study and impact of new energy limits

Background and purpose: Accelerator-Based Boron Neutron Capture Therapy is a radiotherapy based on compact accelerator neutron sources requiring an epithermal neutron field for tumour irradiations. Neutrons of 10 keV are considered as the maximum optimised energy to treat deep-seated tumours. We investigated, by means of Monte Carlo simulations, the epithermal range from 10 eV to 10 keV in order to optimise the maximum epithermal neutron energy as a function of the tumour depth.Methods: A Snyder head phantom was simulated and mono-energetic neutrons with 4 different incident energies were used: 10 eV, 100 eV, 1 keV and 10 keV. ¹⁰B capture rates and absorbed dose composition on every tissue were calculated to describe and compare the effects of lowering the maximum epithermal energy. The Therapeutic Gain (TG) was estimated considering the whole brain volume.Results: For tumours seated at 4 cm depth, 10 eV, 100 eV and 1 keV neutrons provided respectively 54%, 36% and 18% increase on the TG compared to 10 keV neutrons. Neutrons with energies between 10 eV and 1 keV provided higher TG than 10 keV neutrons for tumours seated up to 6.4 cm depth inside the head. The size of the tumour does not change these results.Conclusions: Using lower epithermal energy neutrons for AB-BNCT tumour irradiation could improve treatment efficacy, delivering more therapeutic dose while reducing the dose in healthy tissues. This could lead to new Beam Shape Assembly designs in order to optimise the BNCT irradiation.     

Boron neutron capture therapy using 10B entrapped anti-CEA immunoliposome

A new murine monoclonal antibody (2C-8) was prepared by immunizing mice ip with CEA producing human pancreatic cancer cell line, AsPC-1.SDS-PAGE and Western blot analysis showed that 2C-8 monoclonal antibody recognized CEA and NCA. This anti-CEA monoclonal antibody was conjugated with large multilamellar liposomes incorporated 10B compound (Cs2 10B12H11SH). This immunoliposomes applicated to boron neutron capture therapy. AsPC-1 cells were incubated with the 10B-Lip-MoAb(CEA) for 8 hours. After the irradiation with thermal neutron (1 x 10(11)-1 x 10(13) n/cm2), boronated AsPC-1 cells were showed decreasing uptake of 3H-TdR compared with control group. The numbers of 10B atoms in liposomes bound to an antibody were in proportion to the dose of 10B compounds added and maximum number of 10B atoms was approximatory 1.2 x 10(4)/Ab. These data indicated that the immunoliposomes could deliver highly amount of 10B atoms to the tumor cells and exert cytotoxic effect by thermal neutron. BNCT with immunoliposome may be useful to the non resectable malignant tumors in clinical application.     

Development of Monte Carlo based real-time treatment planning system with fast calculation algorithm for boron neutron capture therapy

PurposeWe simulated the effect of patient displacement on organ doses in boron neutron capture therapy (BNCT). In addition, we developed a faster calculation algorithm (NCT high-speed) to simulate irradiation more efficiently.MethodsWe simulated dose evaluation for the standard irradiation position (reference position) using a head phantom. Cases were assumed where the patient body is shifted in lateral directions compared to the reference position, as well as in the direction away from the irradiation aperture.For three groups of neutron (thermal, epithermal, and fast), flux distribution using NCT high-speed with a voxelized homogeneous phantom was calculated. The three groups of neutron fluxes were calculated for the same conditions with Monte Carlo code. These calculated results were compared.ResultsIn the evaluations of body movements, there were no significant differences even with shifting up to 9 mm in the lateral directions. However, the dose decreased by about 10% with shifts of 9 mm in a direction away from the irradiation aperture.When comparing both calculations in the phantom surface up to 3 cm, the maximum differences between the fluxes calculated by NCT high-speed with those calculated by Monte Carlo code for thermal neutrons and epithermal neutrons were 10% and 18%, respectively. The time required for NCT high-speed code was about 1/10th compared to Monte Carlo calculation.ConclusionsIn the evaluation, the longitudinal displacement has a considerable effect on the organ doses.We also achieved faster calculation of depth distribution of thermal neutron flux using NCT high-speed calculation code.     

Relative biological effectiveness (RBE) of low-dose californium-252

Relative biological effectiveness (RBE) of 252Cf, with respect to 192Ir, has been determined at the low dose rates commonly used in interstitial and intracavitary therapy. The biological criterion was growth reduction in Vicia faba bean roots. Two varieties of Vicia faba were used. For Vicia faba Sutton's seeds, an RBE of 5.7 to 6.6 was obtained for 252Cf Dn + gamma doses of 0.5 to 0.2 Gy respectively and at a Dn + gamma dose rate of 0.11 Gy-1. The gamma contribution D gamma/Dn + gamma at the level of the root tipes was 0.35 and the derived RBE of the neutron emission of 252Cf was then 8.2 to 9.7. For Vicia faba Be1B and in the same irradiation conditions, an RBE of 5.1 to 6.2 was obtained for the total (n + gamma) 252Cf emission and for Dn + gamma doses of 0.4 to 0.2 Gy respectively. These values lead to an RBE of 7.4 to 9.0 for the neutron emission of 252Cf. For Vicia faba BelB, but for another source arrangement (Dn + gamma dose rate of 0.13 Gy . h-1 for 252Cf), an RBE of 5.6 to 7.5 was obtained for the total (n + gamma) emission of 252Cf and for Dn + gamma doses of 0.4 to 0.1 Gy respectively. The gamma contribution (D gamma/Dn + gamma) at the level of the root tips was 0.42, and the derived RBE of the neutron emission of 252Cf was then 8.9-12.3.     

Response of SOI microdosimeter in fast neutron beams: experiment and Monte Carlo simulations

In this study, Monte Carlo codes, Geant4 and MCNP6, were used to characterize the fast neutron therapeutic beam produced at iThemba LABS in South Africa. Experimental and simulation results were compared using the latest generation of Silicon on Insulator (SOI) microdosimeters from the Centre for Medical Radiation Physics (CMRP). Geant4 and MCNP6 were able to successfully model the neutron gantry and simulate the expected neutron energy spectrum produced from the reaction by protons bombarding a ⁹Be target. The neutron beam was simulated in a water phantom and its characteristics recorded by the silicon microdosimeters; bare and covered by a ¹⁰B enriched boron carbide converter, at different positions. The microdosimetric quantities calculated using Geant4 and MCNP6 are in agreement with experimental measurements. The thermal neutron sensitivity and production of ¹⁰B capture products in the p+ boron-implanted dopant regions of the Bridge microdosimeter is investigated. The obtained results are useful for the future development of dedicated SOI microdosimeters for Boron Neutron Capture Therapy (BNCT). This paper provides a benchmark comparison of Geant4 and MCNP6 capabilities in the context of further applications of these codes for neutron microdosimetry.     

Tumor induction in BALB/c female mice after fission neutron or gamma irradiation

This study was designed to examine the dose-response relationships for tumor induction after neutron irradiation in female BALB/c mice, with emphasis on the response in the dose range 0 to 50 rad. Tumors induced after radiation exposure included ovarian tumors, lung adenocarcinomas, and mammary adenocarcinomas. For comparison the dose responses for induction of these tumors after 137Cs gamma irradiation were also examined. As previously described for the female RFM mouse, the data for ovarian tumor induction after neutron and gamma irradiation were consistent with a threshold model. For lung and mammary tumors the dose-response curve after neutron irradiation appeared to "bend over" in the dose range 10 to 20 rad. The factors responsible for this bend-over and their relative contributions to the overall form of the dose-response relationship are not presently known. However, these data strongly indicate that extrapolation from data above 50 rad could result in a significant underestimate of risks. Further, it is clear that current models of neutron carcinogenesis are inadequate, since such a bend-over is not predicted at these low dose levels.     

Simulation of neutron interactions at the single-cell level

We recently reported that the exposure of cancer cells to 14 MeV neutrons at a very low dose rate (0.8 mGy min(-1)) produced a marked increase in cell killing at 5 cGy, followed by a plateau in survival and chromosomal damage. Simulation of the energy deposition events in irradiated cells may help to explain these unusual cell responses. We describe here a Monte Carlo simulation code, Energy Deposition in Cells Irradiated by Neutrons (EDCIN). The procedure considered the experimental setup and a hemispheric cell model. The simulation data fitted the dosimetric measurements performed using tissue-equivalent ionization chambers, Geiger-Müller counters, fission chambers, and silicon diodes. The simulation showed that 80% of the energy deposited in a single cell came from the interactions of neutrons outside the cell and only 20% came from neutron interactions inside the cell. Thus the "external" interactions that result in the production of recoil protons and secondary electrons may induce most of the biological damage, which may be repaired efficiently at low dose rate. The repair process may be triggered from a threshold level of damage, which would explain an initial increase cell death due to unrepaired sublethal damage, and then may compensate for induced damage, resulting in the plateaus.     

Variation in lunar neutron dose estimates

The radiation environment on the Moon includes albedo neutrons produced by primary particles interacting with the lunar surface. In this work, HZETRN2010 is used to calculate the albedo neutron contribution to effective dose as a function of shielding thickness for four different space radiation environments and to determine to what extent various factors affect such estimates. First, albedo neutron spectra computed with HZETRN2010 are compared to Monte Carlo results in various radiation environments. Next, the impact of lunar regolith composition on the albedo neutron spectrum is examined, and the variation on effective dose caused by neutron fluence-to-effective dose conversion coefficients is studied. A methodology for computing effective dose in detailed human phantoms using HZETRN2010 is also discussed and compared. Finally, the combined variation caused by environmental models, shielding materials, shielding thickness, regolith composition and conversion coefficients on the albedo neutron contribution to effective dose is determined. It is shown that a single percentage number for characterizing the albedo neutron contribution to effective dose can be misleading. In general, the albedo neutron contribution to effective dose is found to vary between 1-32%, with the environmental model, shielding material and shielding thickness being the driving factors that determine the exact contribution. It is also shown that polyethylene or other hydrogen-rich materials may be used to mitigate the albedo neutron exposure.     

Characterization of neutron beams for boron neutron capture therapy: in-air radiobiological dosimetry

The survival curves and the RBE for the dose components generated in boron neutron capture therapy (BNCT) were determined separately in neutron beams at Japan Research Reactor No. 4. The surviving fractions of V79 Chinese hamster cells with or without 10B were obtained using an epithermal neutron beam (ENB), a mixed thermal-epithermal neutron beam (TNB-1), and a thermal (TNB-2) neutron beam; these beams were used or are planned for use in BNCT clinical trials. The cell killing effect of the neutron beam in the presence or absence of 10B was highly dependent on the neutron beam used and depended on the epithermal and fast-neutron content of the beam. The RBEs of the boron capture reaction for ENB, TNB-1 and TNB-2 were 4.07 +/- 0.22, 2.98 +/- 0.16 and 1.42 +/- 0.07, respectively. The RBEs of the high-LET dose components based on the hydrogen recoils and the nitrogen capture reaction were 2.50 +/- 0.32, 2.34 +/- 0.30 and 2.17 +/- 0.28 for ENB, TNB-1 and TNB-2, respectively. The RBEs of the neutron and photon components were 1.22 +/- 0.16, 1.23 +/- 0.16, and 1.21 +/- 0.16 for ENB, TNB-1 and TNB-2, respectively. The approach to the experimental determination of RBEs outlined in this paper allows the RBE-weighted dose calculation for each dose component of the neutron beams and contributes to an accurate inter-beam comparison of the neutron beams at the different facilities employed in ongoing and planned BNCT clinical trials.     

Relative biological effectiveness (RBE) of thermal neutron capture therapy of cultured B-16 melanoma cells preincubated with 10B-paraboronophenylalanine

An experimental study of the relative biological effectiveness (RBE) of thermal neutron capture therapy (TNCT) for melanoma cell inactivation using 10B1-paraboronophenylalanine (10B1-BPA) was carried out to demonstrate a high therapeutic effect of TNCT, compared with that of fast neutron. Cells preincubated with or without 10B1-BPA at a concentration of 50 micrograms/ml for 20 h were irradiated with 60Co gamma-ray, fast neutron or thermal neutron. The absorbed dose of the cells from thermal neutron was calculated by Kobayashi's model. The D0 value of fast neutron was 1.07 Gy, and the D0S of thermal neutron radiation with or without preincubation of the cells with 10B1-BPA were 0.46 Gy or 0.67 Gy, respectively. The RBEs of fast neutron, thermal neutron beams, and neutron capture therapy relative to 60Co gamma-ray were calculated as 2.78, 4.18, and 6.15 at 0.1 surviving fraction, respectively. These results indicate radiologically that thermal neutron capture therapy using 10B1-BPA is an excellent radiation therapy for malignant melanoma.     

Assessment of the neutron dose field around a biomedical cyclotron: FLUKA simulation and experimental measurements

In the planning of a new cyclotron facility, an accurate knowledge of the radiation field around the accelerator is fundamental for the design of shielding, the protection of workers, the general public and the environment.Monte Carlo simulations can be very useful in this process, and their use is constantly increasing. However, few data have been published so far as regards the proper validation of Monte Carlo simulation against experimental measurements, particularly in the energy range of biomedical cyclotrons.In this work a detailed model of an existing installation of a GE PETtrace 16.5 MeV cyclotron was developed using FLUKA. An extensive measurement campaign of the neutron ambient dose equivalent H¹(10) in marked positions around the cyclotron was conducted using a neutron rem-counter probe and CR39 neutron detectors. Data from a previous measurement campaign performed by our group using TLDs were also re-evaluated.The FLUKA model was then validated by comparing the results of high-statistics simulations with experimental data. In 10 out of 12 measurement locations, FLUKA simulations were in agreement within uncertainties with all the three different sets of experimental data; in the remaining 2 positions, the agreement was with 2/3 of the measurements.Our work allows to quantitatively validate our FLUKA simulation setup and confirms that Monte Carlo technique can produce accurate results in the energy range of biomedical cyclotrons.