Abstract
Using a 50-kV INTRABEAM® system after breast-conserving surgery, breast skin injury and long treatment time remain the challenging problems when large-size spherical applicators are used. This study has aimed to address these problems using gold (Au) nanoparticles (NPs). For this, surface and isotropic doses were measured using a Gafchromic EBT3 film and a water phantom. The particle propagation code EGSnrc/Epp was used to score the corresponding doses using a geometry similar to that used in the measurements. The simulation was validated using a gamma index of 2%/2 mm acceptance criterion in the gamma analysis. After validation Au-NP-enriched breast tissue was simulated to quantify any breast skin dose reduction and shortening of treatment time. It turned out that the gamma value deduced for validation of the simulation was in an acceptable range (i.e., less than one). For 20 mg-Au/g-breast tissue, the calculated Dose Enhancement Ratio (DER) of the breast skin was 0.412 and 0.414 using applicators with diameters of 1.5 cm and 5 cm, respectively. The corresponding treatment times were shortened by 72.22% and 72.30% at 20 mg-Au/g-breast tissue concentration, respectively. It is concluded that Au-NP-enriched breast tissue shows significant advantages, such as reducing the radiation dose received by the breast skin as well as shortening the treatment time. Additionally, the DERs were not significantly dependent on the size of the applicators.
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References
Albayedh F, Chow JCL (2018) Monte carlo simulation on the imaging contrast enhancement in nanoparticle-enhanced radiotherapy. J Med Phys 43:195–199. https://doi.org/10.4103/jmp.JMP_141_17
Al-Musywel HA, Laref A (2017) Effect of gold nanoparticles on radiation doses in tumor treatment: a Monte Carlo study. Lasers Med Sci 32:2073–2080. https://doi.org/10.1007/s10103-017-2329-0
Archambault JP, Mainegra-Hing E (2015) Comparison between EGSnrc, Geant4, MCNP5 and Penelope for mono-energetic electron beams. Phys Med Biol 60:4951–4962. https://doi.org/10.1088/0031-9155/60/13/4951
Asadi S, Vaez-zadeh M, Masoudi SF, Rahmani F, Knaup C, Meigooni AS (2015) Gold nanoparticle-based brachytherapy enhancement in choroidal melanoma using a full Monte Carlo model of the human eye. J Appl Clin Med Phys 16:344–357. https://doi.org/10.1120/jacmp.v16i5.5568
Avanzo M, Pirrone G, Mileto M, Massarut S, Stancanello J, Baradaran-Ghahfarokhi M, Rink A, Barresi L, Vinante L, Piccoli E, Trovo M, El Naqa I, Sartor G (2019) Prediction of skin dose in low-kV intraoperative radiotherapy using machine learning models trained on results of in vivo dosimetry. Med Phys 46:1447–1454. https://doi.org/10.1002/mp.13379
Baziar O, Gholamhosseinian H, Forghani M (2018) Skin dose assessment with treatment planning system (TPS) and skin reaction evaluation of early breast cancer patients treated via an intraoperative radiation therapy (IORT) device. J Radioth Pract 17:1–5. https://doi.org/10.1017/S1460396918000237
Borca VC, Pasquino M, Russo G, Grosso P, Cante D, Sciacero P, Girelli G, Porta MRL, Tofani S (2013) Dosimetric characterization and use of GAFCHROMIC EBT3 film for IMRT dose verification. J Appl Clin Med Phys 14:158–171. https://doi.org/10.1120/jacmp.v14i2.4111
Bouzid D, Bert J, Dupre PF, Benhalouche S, Pradier O, Boussion N, Visvikis D (2015a) Monte-Carlo dosimetry for intraoperative radiotherapy using a low energy x-ray source. Acta Oncol 54:1788–1795. https://doi.org/10.3109/0284186x.2015.1016623
Bouzid D, Bert J, Dupre PF, Benhalouche S, Pradier O, Boussion N, Visvikis D (2015b) Monte-Carlo dosimetry for intraoperative radiotherapy using a low energy x-ray source. Acta Oncol 54:1788–1795. https://doi.org/10.3109/0284186x.2015.1016623
Bromma K, Cicon L, Beckham W, Chithrani DB (2020) Gold nanoparticle mediated radiation response among key cell components of the tumour microenvironment for the advancement of cancer nanotechnology. Scientif Rep 10:12096. https://doi.org/10.1038/s41598-020-68994-0
Brown TAD, Hogstrom KR, Alvarez D, Matthews KL, Ham K, Dugas JP (2012) Dose-response curve of EBT, EBT2, and EBT3 radiochromic films to synchrotron-produced monochromatic x-ray beams. Med Phys 39:7412–7417. https://doi.org/10.1118/1.4767770
Chetty IJ, Rosu M, Kessler ML, Fraass BA, Ten Haken RK, Kong FM, McShan DL (2006) Reporting and analyzing statistical uncertainties in Monte Carlo-based treatment planning. Int J Radiat Oncol Biol Phys 65:1249–1259. https://doi.org/10.1016/j.ijrobp.2006.03.039
Cho SH (2005) Estimation of tumour dose enhancement due to gold nanoparticles during typical radiation treatments: a preliminary Monte Carlo study. Phys Med Biol 50:N163-173. https://doi.org/10.1088/0031-9155/50/15/n01
Choi J, Kim G, Cho SB, Im H-J (2020) Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme. J Nanobiotechnol 18:122. https://doi.org/10.1186/s12951-020-00684-5
Chow J (2018a) Recent progress in Monte Carlo simulation on gold nanoparticle radiosensitization AIMS. Biophysics 5:231–244. https://doi.org/10.3934/biophy.2018.4.231
Chow JCL (2018b) Recent progress in Monte Carlo simulation on gold nanoparticle radiosensitization. AIMS Biophysics
Chun He JCLC (2016) Gold nanoparticle DNA damage in radiotherapy: A Monte Carlo study. AIMS Bioeng
Cui C, Lippuner J, Ingleby H, Valentino D, Elbakri I (2010) Epp - A C++ EGSnrc user code for monte carlo simulation of radiation transport. Prog Biomed Opt Imaging Proc SPIE. https://doi.org/10.1117/12.844419
Devic S, Seuntjens J, Sham E, Podgorsak EB, Schmidtlein CR, Kirov AS, Soares CG (2005) Precise radiochromic film dosimetry using a flat-bed document scanner. Med Phys 32:2245–2253. https://doi.org/10.1118/1.1929253
Devic S, Tomic N, Aldelaijan S, Deblois F, Seuntjens J, Chan M, Lewis D (2012a) Linearization of dose response curve of the radiochromic film dosimetry system. Med Phys 39:4850–4857. https://doi.org/10.1118/1.4736800
Devic S, Tomic N, Aldelaijan S, Deblois F, Seuntjens J, Chan MF, Lewis D (2012b) Linearization of dose-response curve of the radiochromic film dosimetry system. Med Phys 39:4850–4857. https://doi.org/10.1118/1.4736800
Eaton DJ (2012) Quality assurance and independent dosimetry for an intraoperative x-ray device. Med Phys 39:6908–6920. https://doi.org/10.1118/1.4761865
Farah N, Francis Z, Abboud M (2014) Analysis of the EBT3 Gafchromic film irradiated with 6 MV photons and 6 MeV electrons using reflective mode scanners. Phys Med 30:708–712. https://doi.org/10.1016/j.ejmp.2014.04.010
Fogg P, Das KR, Kron T, Fox C, Chua B, Hagekyriakou J (2010) Thermoluminescence dosimetry for skin dose assessment during intraoperative radiotherapy for early breast cancer. Australas Phys Eng Sci Med 33:211–214. https://doi.org/10.1007/s13246-010-0019-3
Geleijns J, Wondergem J (2005) X-ray imaging and the skin: radiation biology, patient dosimetry and observed effects. Radiat Prot Dosimetry 114:121–125. https://doi.org/10.1093/rpd/nch544
Ghaghada KB, Starosolski ZA, Lakoma A, Kaffes C, Agarwal S, Athreya KK, Shohet J, Kim E, Annapragada A (2016) Heterogeneous uptake of nanoparticles in mouse models of pediatric high-risk neuroblastoma. PLoS ONE 11:e0165877. https://doi.org/10.1371/journal.pone.0165877
Ghorbani M, Bakhshabadi M, Golshan A, Knaup C (2013) Dose enhancement by various nanoparticles in prostate brachytherapy Australasian. Assoc Phys Sci Med. https://doi.org/10.1007/s13246-013-0231-z
Hainfeld JF, Slatkin DN, Smilowitz HM (2004) The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol 49:N309-315. https://doi.org/10.1088/0031-9155/49/18/n03
Hainfeld JF, Dilmanian FA, Zhong Z, Slatkin DN, Kalef-Ezra JA, Smilowitz HM (2010) Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma. Phys Med Biol 55:3045–3059. https://doi.org/10.1088/0031-9155/55/11/004
Hariri Tabrizi S, Heidarloo N, Tavallaie M (2020) Introduction of a reliable software for the calculation of the gamma index iranian. J Med Phys 17:133–136. https://doi.org/10.22038/ijmp.2019.39178.1557
Holmes DR (2017) Early complications after intraoperative radiotherapy revisited. J Surg Oncol 115:779–781. https://doi.org/10.1002/jso.24590
Howard ME, Herman MG, Grams MP (2020) Methodology for radiochromic film analysis using FilmQA pro and ImageJ. PLoS ONE 15:e0233562. https://doi.org/10.1371/journal.pone.0233562
Huang S-Y, Boone JM, Yang K, Kwan ALC, Packard NJ (2008) The effect of skin thickness determined using breast CT on mammographic dosimetry. Med Phys 35:1199–1206. https://doi.org/10.1118/1.2841938
Hugtenburg RP (2010) Dosimetry of microdistributed dose-enhancing agents in X-ray synchrotron binary therapy. 6th international conference on medical applications of synchrotron radiation. Siu KKW. 1266: 98–100.
Janic B, Brown SL, Neff R, Liu F, Mao G, Chen Y, Jackson L, Chetty IJ, Movsas B, Wen N (2021) Therapeutic enhancement of radiation and immunomodulation by gold nanoparticles in triple negative breast cancer. Can Biol Ther 22:124–135. https://doi.org/10.1080/15384047.2020.1861923
Jaschke W, Schmuth M, Trianni A, Bartal G (2017) Radiation-induced skin injuries to patients: what the interventional radiologist needs to know. Cardiovasc Interv Radiol 40:1131–1140. https://doi.org/10.1007/s00270-017-1674-5
Jones BL, Krishnan S, Cho SH (2010) Estimation of microscopic dose enhancement factor around gold nanoparticles by Monte Carlo calculations. Med Phys 37:3809–3816. https://doi.org/10.1118/1.3455703
Kakade NR, Sharma SD (2015) Dose enhancement in gold nanoparticle-aided radiotherapy for the therapeutic photon beams using Monte Carlo technique. J Cancer Res Ther 11:94–97. https://doi.org/10.4103/0973-1482.147691
Khoo AM, Cho SH, Reynoso FJ, Aliru M, Aziz K, Bodd M, Yang X, Ahmed MF, Yasar S, Manohar N, Cho J, Tailor R, Thames HD, Krishnan S (2017) Radiosensitization of prostate cancers in vitro and in vivo to erbium-filtered orthovoltage X-rays using actively targeted gold nanoparticles. Scient Rep 7:18044. https://doi.org/10.1038/s41598-017-18304-y
Kraus-Tiefenbacher U, Steil V, Bauer L, Melchert F, Wenz F (2003) A novel mobile device for intraoperative radiotherapy (IORT). Onkologie 26:596–598. https://doi.org/10.1159/000074158
Liu D, Auguste DT (2015) Cancer targeted therapeutics: from molecules to drug delivery vehicles. J Control Release 219:632–643. https://doi.org/10.1016/j.jconrel.2015.08.041
Low DA, Dempsey JF (2003) Evaluation of the gamma dose distribution comparison method. Med Phys 30:2455–2464. https://doi.org/10.1118/1.1598711
Low DA, Harms WB, Mutic S, Purdy JA (1998) A technique for the quantitative evaluation of dose distributions. Med Phys 25:656–661. https://doi.org/10.1118/1.598248
Martelli S, Chow JC (2020) Dose enhancement for the flattening-filter-free and flattening-filter photon beams in nanoparticle-enhanced radiotherapy: a monte carlo phantom study. Nanomaterials. https://doi.org/10.3390/nano10040637
Martinov MP, Thomson RM (2017) Heterogeneous multiscale Monte Carlo simulations for gold nanoparticle radiosensitization. Med Phys 44:644–653. https://doi.org/10.1002/mp.12061
Massillon-Jl G, Chiu-Tsao S-T, Muñoz I, Chan M (2012) Energy dependence of the new gafchromic EBT3 film: dose response curves for 50 kV, 6 and 15 MV X-Ray beams. Internat J Med Phys Clin Eng Radiat Oncol 1:60–65. https://doi.org/10.4236/ijmpcero.2012.12008
Mohammadi K, Hassani M, Ghorbani M, Farhood B, Knaup C (2017) Evaluation of the accuracy of various dose calculation algorithms of a commercial treatment planning system in the presence of hip prosthesis and comparison with Monte Carlo. J Cancer Res Ther 13:501–509. https://doi.org/10.4103/0973-1482.204903
Moradi F, Ung NM, Khandaker MU, Mahdiraji GA, Saad M, Abdul Malik R, Bustam AZ, Zaili Z, Bradley DA (2017a) Monte Carlo skin dose simulation in intraoperative radiotherapy of breast cancer using spherical applicators. Phys Med Biol 62:6550–6566
Ngwa W, Kumar R, Sridhar S, Korideck H, Zygmanski P, Cormack RA, Berbeco R, Makrigiorgos GM (2014) Targeted radiotherapy with gold nanoparticles: current status and future perspectives. Nanomedicine (Lond) 9:1063–1082. https://doi.org/10.2217/nnm.14.55
Njeh CF, Saunders MW, Langton CM (2010) Accelerated partial breast irradiation (APBI): a review of available techniques. Radiat Oncol 5:90. https://doi.org/10.1186/1748-717X-5-90
Nwankwo O, Clausen S, Schneider F, Wenz F (2013) A virtual source model of a kilo-voltage radiotherapy device. Phys Med Biol 58:2363–2375. https://doi.org/10.1088/0031-9155/58/7/2363
Paro AD, Hossain M, Webster TJ, Su M (2016) Monte Carlo and analytic simulations in nanoparticle-enhanced radiation therapy. Int J Nanomed 11:4735–4741. https://doi.org/10.2147/IJN.S114025
Pérez-Herrero E, Fernández-Medarde A (2015) Advanced targeted therapies in cancer: drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm 93:52–79. https://doi.org/10.1016/j.ejpb.2015.03.018
Price C, Pederson A, Frazier C, Duttenhaver J (2013) In vivo dosimetry with optically stimulated dosimeters and RTQA2 radiochromic film for intraoperative radiotherapy of the breast. Med Phys. https://doi.org/10.1118/1.4819825
Rieux A, Pourcelle V, Cani PD, Marchand-Brynaert J, Préat V (2013) Targeted nanoparticles with novel non-peptidic ligands for oral delivery. Adv Drug Deliv Rev 65:833–844. https://doi.org/10.1016/j.addr.2013.01.002
Saha RN, Vasanthakumar S, Bende G, Snehalatha M (2010) Nanoparticulate drug delivery systems for cancer chemotherapy. Mol Membr Biol 27:215–231. https://doi.org/10.3109/09687688.2010.510804
Schneider F, Greineck F, Clausen S, Mai S, Obertacke U, Reis T, Wenz F (2011) Development of a novel method for intraoperative radiotherapy during kyphoplasty for spinal metastases (Kypho-IORT). Int J Radiat Oncol Biol Phys 81:1114–1119. https://doi.org/10.1016/j.ijrobp.2010.07.1985
Schneider U, Pedroni E, Lomax A (1996) The calibration of CT Hounsfield units for radiotherapy treatment planning.
Sedlmayer F, Fastner G, Merz F, Deutschmann H, Reitsamer R, Menzel C, Ciabattoni A, Petrucci A, Hager E, Willich N, Orecchia R, Valentini V and International Society of Intraoperative R (2007) IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: results of an ISIORT pooled analysis Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 183 Spec No 2:32–34 doi:https://doi.org/10.1007/s00066-007-2013-6
Sethi A, Emami B, Small W Jr, Thomas TO (2018) Intraoperative radiotherapy with intrabeam: technical and dosimetric considerations. Front Oncol 8:74. https://doi.org/10.3389/fonc.2018.00074
Shaikh MY, Tanny S (2020) Dosimetric comparison of the INTRABEAM and Axxent for intraoperative breast radiotherapy. Brachytherapy 19:234–240. https://doi.org/10.1016/j.brachy.2019.11.005
Shamsabadi R, Baghani HR, Azadegan B, Mowlavi AA (2020) Monte Carlo based analysis and evaluation of energy spectrum for low-kV IORT spherical applicators. Z Med Phys 30:60–69. https://doi.org/10.1016/j.zemedi.2019.08.002
Siddique S, Chow JCL (2020a) Application of nanomaterials in biomedical imaging and cancer. Ther Nanomater. https://doi.org/10.3390/nano10091700
Siddique S, Chow JCL (2020b) Gold nanoparticles for drug delivery and cancer. Ther Appl Sci. https://doi.org/10.3390/app10113824
Sim GS, Wong JHD, Ng KH (2013) The use of radiochromic EBT2 film for the quality assurance and dosimetric verification of 3D conformal radiotherapy using Microtek ScanMaker 9800XL flatbed scanner. J Appl Clin Med Phys 14:4182–4182. https://doi.org/10.1120/jacmp.v14i4.4182
Sorriaux J, Kacperek A, Rossomme S, Lee JA, Bertrand D, Vynckier S, Sterpin E (2013) Evaluation of Gafchromic® EBT3 films characteristics in therapy photon, electron and proton beams. Phys Med 29:599–606. https://doi.org/10.1016/j.ejmp.2012.10.001
Tchoryk A, Taresco V, Argent RH, Ashford M, Gellert PR, Stolnik S, Grabowska A, Garnett MC (2019) Penetration and uptake of nanoparticles in 3D tumor spheroids bioconjugate. Chemistry 30:1371–1384. https://doi.org/10.1021/acs.bioconjchem.9b00136
Tegaw EM, Geraily G, Etesami SM, Ghanbari H, Gholami S, Shojaei M, Farzin M, Tadesse GF (2021) Dosimetric effect of nanoparticles in the breast cancer treatment using INTRABEAM(®)system with spherical applicators in the presence of tissue heterogeneities: a Monte Carlo study. Biomed Phys Eng Express. https://doi.org/10.1088/2057-1976/abf6a9
White DR, Booz J, Griffith RV, Spokas JJ, Wilson IJ (1989) Report 44. J Internat Comm Radiat Units Measure. https://doi.org/10.1093/jicru/os23.1.Report44
Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H (2012) Nanoparticles as drug delivery systems. Pharmacol Rep 64:1020–1037. https://doi.org/10.1016/s1734-1140(12)70901-5
Woodard HQ, White DR (1986) The composition of body tissues. Br J Radiol 59:1209–1218. https://doi.org/10.1259/0007-1285-59-708-1209
Yu B, Tai HC, Xue W, Lee LJ, Lee RJ (2010) Receptor-targeted nanocarriers for therapeutic delivery to cancer. Mol Membr Biol 27:286–298. https://doi.org/10.3109/09687688.2010.521200
Zhang DG, Feygelman V, Moros EG, Latifi K, Zhang GG (2014) Monte carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy. PLoS ONE 9:e109389. https://doi.org/10.1371/journal.pone.0109389
Zheng X, Chow J (2016) Dose enhancement due to nanoparticle addition in skin radiotherapy: A monte carlo study using kilovoltage photon beams. Med Phys 43:3546
Zheng XJ, Chow JCL (2017) radiation dose enhancement in skin therapy with nanoparticle addition: a monte carlo study on kilovoltage photon and megavoltage electron beams world. J Radiol 9:63–71. https://doi.org/10.4329/wjr.v9.i2.63
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This study was funded and supported by Tehran University of Medical Sciences (TUMS), Tehran, Iran; Grant no 98-01-103-41980.
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All the authors have read and approved the final manuscript. EMT, GG, and SG contributed to conceptualization. EMT and GFT were involved in data curation, formal analysis, and writing – original draft. GFT and GG contributed to investigation. EMT and GG were involved in methodology. EMT contributed to resources and software. GG performed supervision and validation. EMT, GG, and MS were involved in writing – review and editing.
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Tegaw, E.M., Geraily, G., Gholami, S. et al. Gold-nanoparticle-enriched breast tissue in breast cancer treatment using the INTRABEAM® system: a Monte Carlo study. Radiat Environ Biophys 61, 119–131 (2022). https://doi.org/10.1007/s00411-021-00954-2
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DOI: https://doi.org/10.1007/s00411-021-00954-2