

ORIGINAL ARTICLE 

Year : 2019  Volume
: 15
 Issue : 8  Page : 4246 

Effect of Au197 nanoparticles along with Sm153 radiopharmaceutical in prostate cancer from simulation method
Akbar Abbasi^{1}, Fahreddin Sadikoglu^{2}, Mostafa Hassanzadeh^{3}
^{1} Faculty of Engineering, University of Kyrenia, Girne, Turkey; Reactor Research School, Nuclear Science and Technology Institute (NSTRI), Tehran, Iran ^{2} Department of Electrical and Electronic Engineering, Near East University, Nicosia, North Cyprus, Mersin 10, Turkey ^{3} Reactor Research School, Nuclear Science and Technology Institute (NSTRI), Tehran, Iran
Date of Web Publication  22Mar2019 
Correspondence Address: Dr. Akbar Abbasi University of Kyrenia, Kyrenia, North Cyprus, Mersin 10
Source of Support: None, Conflict of Interest: None  Check 
DOI: 10.4103/jcrt.JCRT_183_17
Aims: Based on recent studies, it was indicated that gold (Au197) nanoparticles could be safely prescribed and used to enhance the absorbed dose during radiation therapy. Subjects and Methods: We evaluated the samarium153 (Sm153) radiopharmaceutical and Au197 and Sm153 radiopharmaceutical absorbed dose rate by means of the Monte Carlo technique in prostate cancer. Results: The results show that absorbed dose rate in entire prostate volume due to 20 mCi of Sm153 radiopharmaceutical is 27.339 μGy/s, 48.837 μGy/s, and 76.176 μGy/s for γinteraction, β¯ particle interaction, and γ+β¯ interaction, respectively. The results in the exterior of the prostate for β¯ interaction, β¯ particle interaction, and γ+β¯ interaction were 20.971 μGy/s, 1.110 μGy/s, and 22.081 μGy/s, respectively. Conclusions: The calculation results for Au197 and Sm153 radiopharmaceutical show that the absorbed dose rate in entire prostate volume 3% was increased and undesirable dose value in exterior of prostate 7% was decreased.
Keywords: Absorbed dose, MCNP4C, prostate, radiotherapy, samarium153
How to cite this article: Abbasi A, Sadikoglu F, Hassanzadeh M. Effect of Au197 nanoparticles along with Sm153 radiopharmaceutical in prostate cancer from simulation method. J Can Res Ther 2019;15, Suppl S1:426 
How to cite this URL: Abbasi A, Sadikoglu F, Hassanzadeh M. Effect of Au197 nanoparticles along with Sm153 radiopharmaceutical in prostate cancer from simulation method. J Can Res Ther [serial online] 2019 [cited 2020 Nov 27];15:426. Available from: https://www.cancerjournal.net/text.asp?2019/15/8/42/244440 
> Introduction   
Prostate cancer is the third most common cancer worldwide among males and the fourth in terms of incidence worldwide.^{[1]} Conventional methods of cancer treatment such as normal radiotherapy, surgery, or chemotherapy due to damage healthy cells surrounding cancer cells and leave cancer cells, are not safe and deterministic methods. Protecting healthy cells in the beam path or in the vicinity of cancer cells in tumors during treatment is very important. The study in the United States shows that one in six men or 230,000 new cases of prostate cancer are diagnosed every year, with an estimated 27,000 deaths every year.^{[2]} However, increasing radiation dose in a tumor can improve cell kill, but the effects of radiation often restrict its practical use in patients. Despite all the advances in threedimensional diagnosis, intensity modulated of external radiation, radiotherapy toxicities in the rectum and bladder remaining is a major concern. Thus, it is important to develop novel approaches for enhancing radiation effectiveness in prostate cancer.^{[3],[4]}
Nanoparticles such as Au197 nanoparticles are solid colloidal particles ranging in size from 10 nm to 200 nm that are 10^{2}–10^{4} times smaller than human cells.^{[5]} Nanoparticles between 10 nm and 50 nm are able to pass through cell membranes, and the particles with 20 NM size can pass through blood vessel endothelial.^{[2]}
Samarium153 (Sm153) is a beta and gamma emitter synthetic radioisotope with halflife of 46.7 h. The therapeutic effect of Sm153 arises from the emission of radioisotopes short halflife and desirable particle emission. Sm153 emits three common beta particles including E_{max}= 704 keV (49.4%), E_{max}= 634 keV (31.3%), and E_{max}= 807 keV (18.4%) that are suitable for killing malignant cells. It also emits two gamma photons at E_{γ}=103 keV (29.2%) and E_{γ}=70 keV (4.7%) energy [Figure 1]. Hence, this low energy releasing photon, allow physicians to be aware from distribution and amount of the radionuclide. In addition, the short halflife of Sm153 makes its suitable radionuclide to rapid clearance from the body.
The application of the Monte Carlo simulation technique in brachytherapy and external beam radiation therapy has been demonstrated in some research reports.^{[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18]} The application of the Monte Carlo simulation technique in dosimetry applications can be developed by the availability's of Monte Carlo codes such as MCNP4C code a^{[19]} along with the advancement of biological and physical investigations for more accurate dose and intensity calculations for patient treatment.
The purpose of this research is applying the MCNP4C Monte Carlo code for investigation of the effect of Sm153 radiopharmaceutical composed with Au197 nanoparticles in prostate cancer treatment. Furthermore, a comparison is made between the Au197 nanoparticles effects in prostatesimulated dose contributions.
> Subjects and Methods   
Monte Carlo method
A Monte Carlo Nparticle Transport Code (MCNP4C, version 4C) was used to calculate the doses in the prostate. This code calculates the phenomena of Photoelectric, Compton, and Pairproduction interactions with matter. In the MCNP4C code, there are several tally types available to dose calculation. In this paper, the frequency modulation (FM) (tally multiplier) card was used to calculation of the doses rate. A tally is a specification of what should be included in the problem output. For example, the FM card can modify any flux or current tally or dose rate through the Eq. (1). Thus, to calculation of the dose rate we used the following equation:
Where ϕ (E) is the energydependent fluence (particles/cm^{2}) and R (E) is an operator of additive and/or multiplicative response functions from the MCNP4C code crosssection libraries or specially designated quantities. That the crosssection library used in this code is ENDF/BIV library. The constant C is any arbitrary scalar quantity that can be used for normalization. The material number m must appear on a Mm card but not need to use in a geometrical cell of the problem.
Sm153 sources
The Sm153 source is a beta and gamma emitter source that emits the gamma photon energy in 103 Kiev and 70 keV. The beta particles emit at E_{max}= 704 keV, E_{max}= 634 keV, and E_{max}= 807 keV energy. In this state, the absorbed dose rate has been simulated in the prostate model (4 cm × 3 cm × 2 cm), with 20 mCi value of Sm153 radiopharmaceutical that uniformly distributed in prostate tissue [Figure 2]a.  Figure 2: The prostate simulation modeling distribution (a) samarium153 radiopharmaceutical intake (b) Au197 and samarium153 solution intake
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Au197 and Sm153 sources
The Au197 nanoparticle and Sm153 sources is a mixed solution that contains 20 mCi of Sm153 and 10 ml of Au197 nanoparticles. The Sm153 radionuclide interaction with prostate tissue will be by direct gamma photon interaction and beta particles.
The application of Au197 nanoparticles in the treatment of cancer was reported in some articles.^{[20],[21],[22],[23]} The interaction between gold atoms and beta particles occurs by the bremsstrahlung phenomena. Those interactions are shown in [Figure 2]b and [Figure 3].  Figure 3: Au197 and samarium153 solution interaction diagram in prostate simulation modeling
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Dose rate calculation
The “F4” tally gives a quantity in unit of particles/cm^{2} per source particle. For dose calculation, we need the “FM” (tally multiplier) card to convert this unit to units of dose. Two basic approaches are useful for converting from flounce quantities to units of dose. One choice is to use a heating number method. The other choice is to fold in one or more flounce to dose conversion function. Both approaches are valid for photon dose calculation, but the use of conversion functions is recommended for electron dose equivalent and effective dose. Thus, we select the heating number method. In the heating number method, MCNP4C calculates absorbed dose on the basis of the KERMA approximation, which assumes that kinetic energy transferred to charge particles is locally deposited.^{[24]}
Using the KERMA approximation, the dose can be represented using the following equation:
The parameter C is calculated by:
Where Nα is Avogadro's number (6.022 × 10^{23} mol ^{−1}); η, number of atoms per molecule; M, molar mass in grams; ϕ, flufluency ore in particles/cm^{2}; σ_{T}, total atomic cross section at energy of scoring track in barns; H, heating number in MeV per collision; T, number of scoring source particle tracks, and N, number of source particles.
> Results   
The absorbed dose rates per se cond Ḋ (μGy/s) due to 20 mCi activity concentration of the Sm153 radiopharmaceutical in entire prostate volume and its exterior were calculated by MCNP4C code and are shown in [Table 1]. This calculation is results of interaction between the main gamma photon energy in 103 Kev and 70 keV, and three beta particles at E_{max}= 704 keV, E_{max}= 634 keV, and E_{max}= 807 keV energy, that emitted by Sm153 in prostate tissue. The accuracy of the code input data to calculate the absorbed dose rates at all cases are considered the number of particles history 2.5 × 10^{6} with relative error of 0.9%. The simulated results of photons and particle tracks in prostate and outside of prostate tissue are shown in [Figure 4].  Table 1: The absorbed dose rates due to 20 mCi activity concentration of Sm153 radiopharmaceutical in the entire and exterior prostate volume
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 Figure 4: The MCNP4C simulated tracks of photons and β particles in prostate and outside of prostate tissue
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As shown in the results of the absorbed dose rate due to β¯ particles and γ photon in entire prostate volume are higher than in the exterior of the prostate. The total absorbed dose rate in entire prostate volume and in exterior of the prostate is 76.176 ± 0.032 μGy/s and 22.081 ± 0.028 μGy/s, respectively.
Furthermore, the absorbed dose rate per se cond of 20 mCi activity concentration of Sm153 radiopharmaceutical along with Au197 nanoparticle has been estimated by MCNP4C code, and the obtained results are shown in [Table 2].  Table 2: The absorbed doses rate of Sm153 along with Au197 nanoparticle in the entire and exterior prostate volume
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The calculation results show that Au197 nanoparticles along with Sm153 can increase the absorbed dose rates in entire prostate volume and decrease the absorbed dose rate in the exterior of the prostate. The calculated values for photon interaction in entire prostate volume and in exterior of prostate are 27.387 ± 0.021 μGy/s and 18.627 ± 0.012 μGy/s, respectively. Furthermore, the absorbed dose rate magnitude due to β¯ particle interaction in entire and exterior of prostate are 51.241 ± 0.032 μGy/s and 1.890 ± 0.058 μGy/s, respectively. As well as the total absorbed dose rates in entire prostate volume are 78.627 ± 0.024 μGy/s, and this parameter in the exterior of the prostate is 20.517 ± 0.079 μGy/s. Finally, this increased absorbed dose rate due to bremsstrahlung phenomena of β particles with Au197 atoms.
[Figure 5] shows a comparison between the Sm153 radiopharmaceutical intake and the Sm153 along with Au197 nanoparticle usage for dose calculation by Monte Carlo MCNP4C code. These results show that the effect of Au197 nanoparticle along with Sm153 is in beta interaction more than gamma interaction.  Figure 5: The comparison of simulation absorbed dose results in entire and the exterior of the prostate
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> Discussion   
The Au197 nanoparticle treatment for a sample prostate model was successfully performed using the Monte Carlo MCNP4C code. In these calculations, it was found that the Au197 and Sm153 sources can be optimizing the absorbed dose rate in prostate tumor treatment. The increasing dose value in the entire prostate volume is about 3% and decreasing undesirable dose value in exterior of the prostate is 7%. Therefore, using the Au197 nanoparticle in prostate cancer treatment has an effective role. A comparison between the results shows that the effect of Au197 nanoparticle along with Sm153 is in beta interaction more than gamma interaction. This difference is about 8%–0.2%. In summary, the results of this investigation is support the Monte Carlo simulation technique with the data presented by Cho;^{[18]} as reported in this research, the effect of Au197 nanoparticles in absorbed dose due to ^{192}Ir gamma rays is 2% on average.
> Conclusion   
In conclusion, the results of this investigation shown that Au197 has Effective role in cancer therapy from theoretical view. Au197 and Sm153 mixed radiopharmaceutical indicated that the absorbed dose rate in entire prostate volume 3% was increased and undesirable dose value in exterior of prostate 7% was decreased.
Acknowledgement
This work was carried out between Science and Technology Research Institute (STRI) and University of Kyrenia. Therefore, the authors are very grateful to the cooperation and support of management and staff of STRI.
Financial support and sponsorship
This study was financially supported by University of Kyrenia, Kyrenia, North Cyprus, Mersin 10, Turkey.
Conflicts of interest
There are no conflicts of interest.
> References   
1.  Maffioli L, Florimonte L, Costa DC, Correia Castanheira J, Grana C, Luster M, et al. New radiopharmaceutical agents for the treatment of castrationresistant prostate cancer. Q J Nucl Med Mol Imaging 2015;59:42038. 
2.  Zhang X, Xing JZ, Chen J, Ko L, Amanie J, Gulavita S, et al. Enhanced radiation sensitivity in prostate cancer by goldnanoparticles. Clin Invest Med 2008; 31:1607. 
3.  Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, et al. Longterm results of the M. D. Anderson randomized doseescalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 2008;70:6774. 
4.  Eade TN, Hanlon AL, Horwitz EM, Buyyounouski MK, Hanks GE, Pollack A, et al. What dose of externalbeam radiation is high enough for prostate cancer? Int J Radiat Oncol Biol Phys 2007;68:6829. 
5.  Hainfeld JF, Slatkin DN, Smilowitz HM. The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol 2004;49:N30915. 
6.  Ye SJ, Parsai EI, Feldmeier JJ. Dosimetric characteristics of a linear array of gamma or betaemitting seeds in intravascular irradiation: Monte Carlo studies for the AAPM TG43/60 formalism. Med Phys 2003;30:40314. 
7.  Nelson WR, Hirayama H, Rogers DW. The EGS4 Code System Stanford Linear Accelerator Center. Report SLAC265; 1985. 
8.  Meigooni AS, Gearheart DM, Sowards K. Experimental determination of dosimetric characteristics of best 125I brachytherapy source. Med Phys 2000;27:216873. 
9.  Morin RL. Monte Carlo Simulation in the Radiological Sciences. ISBN 0849355591;1988;19. 
10.  Nath R, Anderson LL, Luxton G, Weaver KA, Williamson JF, Meigooni AS, et al. Dosimetry of interstitial brachytherapy sources: Recommendations of the AAPM Radiation Therapy committee task group no 43. American Association of Physicists in Medicine. Med Phys 1995;22:20934. 
11.  Verhaegen F, Mubata C, Pettingell J, Bidmead AM, Rosenberg I, Mockridge D, et al. Monte Carlo calculation of output factors for circular, rectangular, and square fields of electron accelerators (620 meV). Med Phys 2001;28:93849. 
12.  Zhang H, Baker C, McKinsey R, Meigooni A. Dose verification with Monte Carlo technique for prostate brachytherapy implants with (125) I sources. Med Dosim 2005;30:8591. 
13.  Weaver K. Anisotropy functions for ^{125}I and ^{103}Pd sources. Med Phys 1998;25:22718. 
14.  Hartmann Siantar CL, Walling RS, Daly TP, Faddegon B, Albright N, Bergstrom P, et al. Description and dosimetric verification of the PEREGRINE Monte Carlo dose calculation system for photon beams incident on a water phantom. Med Phys 2001;28:132237. 
15.  Solberg TD, DeMarco JJ, Hugo G, Wallace RE. Dosimetric parameters of three new solid core I125 brachytherapy sources. J Appl Clin Med Phys 2002;3:11934. 
16.  Taghdiri F, Sadeghi M, Hosseini SH, Athari M. TG60 dosimetry parameters calculation for the βemitter ^{153}Sm brachytherapy source using MCNP. Iran J Radiat Res 2011;9:1038. 
17.  Wang L, Chui CS, Lovelock M. A patientspecific Monte Carlo dosecalculation method for photon beams. Med Phys 1998; 25:86778. 
18.  Cho SH. Estimation of tumour dose enhancement due to gold nanoparticles during typical radiation treatments: A preliminary Monte Carlo study. Phys Med Biol 2005;50:N16373. 
19.  Briesmeister JF. MCNPTMA General Monte Carlo Nparticle Transport Code. Version 4C, LA13709M. Los Alamos National Laboratory; 2000. 
20.  Chithrani DB, Jelveh S, Jalali F, van Prooijen M, Allen C, Bristow RG, et al. Gold nanoparticles as radiation sensitizers in cancer therapy. Radiat Res 2010;173:71928. 
21.  Lechtman E, Mashouf S, Chattopadhyay N, Keller BM, Lai P, Cai Z, et al. AMonte Carlobased model of gold nanoparticle radiosensitization accounting for increased radiobiological effectiveness. Phys Med Biol 2013;58:307587. 
22.  Douglass M, Bezak E, Penfold S. Monte Carlo investigation of the increased radiation deposition due to gold nanoparticles using kilovoltage and megavoltage photons in a 3D randomized cell model. Med Phys 2013;40:071710. 
23.  Wolfe T, Chatterjee D, Lee J, Grant JD, Bhattarai S, Tailor R, et al. Targeted gold nanoparticles enhance sensitization of prostate tumors to megavoltage radiation therapy in vivo. Nanomedicine 2015;11:127783. 
24.  Lazarine AD. Medical Physics Calculations with MCNP: A Primer Doctoral Dissertation. Texas A & M University; 2006. 
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]
