Dosimetry of Bone-Seeking Radiopharmaceuticals for Palliative Therapy of Bone Metastases: A Simulation Study Using GATE Monte Carlo Code
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Abstract
Purpose: Radiopharmaceutical Therapy (RPT) is one of the effective methods for pain palliation of bone metastases. Bone marrow is a critical organ in bone structure whose absorbed dose should be kept below a certain threshold. The purpose of this study was to calculate and compare absorbed doses of bone-seeking radiopharmaceuticals used in the palliative treatment of bone metastases.
Materials and Methods: In this study, the GATE Monte Carlo code was used to simulate a femur bone, which consists of bone marrow, endosteal layer, bone, and soft tissue phantom model. Absorbed doses of the 153Sm-EDTMP, 89SrCl2, 177Lu-EDTMP, 188Re-HEDP, and 223RaCl2 radiopharmaceuticals were calculated in the femur phantom compartments.
Results: bone absorbed doses per disintegration from alpha particles of 223RaCl2 is approximately 24 times higher than absorbed doses from beta particles of 89SrCl2. Also, absorbed dose per disintegration from beta particles of 89SrCl2 in the bone is approximately 12, 6 and 1.5 times higher than 177Lu-EDTMP, 153Sm-EDTMP, and 188Re-HEDP, respectively. Moreover, the bone and bone marrow absorbed dose from beta particles of 153Sm-EDTMP is 1.9 times higher than 177Lu-EDTMP. Besides, absorbed dose per disintegration from beta particles of 188Re-HEDP in the bone marrow is approximately 40, 30, 7, and 4 times higher than 223RaCl2, 89SrCl2, 177Lu-EDTMP and 153Sm-EDTMP, respectively.
Conclusion: Our results show that 223RaCl2 could be a more efficient radiopharmaceutical for radionuclide therapy of bone metastases. Also, 177Lu-EDTMP, due to low marrow toxicity and comparable bone absorbed dose with 153Sm-EDTMP, can be used for achieving bone pain palliation. Moreover, significantly high bone marrow absorbed dose of 188Re-HEDP should be considered for palliative therapy of metastatic bone patients.
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31- Goyal, J. and E.S. Antonarakis, "Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastases," Cancer letters, vol. 323, no. 2, pp. 135-146, 2012.
32- Pacilio, M., et al., "Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting 223 Ra-dichloride," European journal of nuclear medicine and molecular imaging, vol. 43, no.1, pp. 21-33, 2016.
33- Parker, C., et al., "Alpha emitter radium-223 and survival in metastatic prostate cancer," New England Journal of Medicine, vol. 369, no. 3, pp. 213-223, 2013.
34- Harrison, M.R., et al., "Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease," Cancer management and research, vol. 5, pp. 1, 2013.
35- Sharma, S., et al., "Comparative therapeutic efficacy of 153Sm-EDTMP and 177Lu-EDTMP for bone pain palliation in patients with skeletal metastases: patients’ pain score analysis and personalized dosimetry," Frontiers in medicine, vol. 4, pp. 46, 2017.
36- Thapa, P., et al., "Clinical efficacy and safety comparison of 177Lu-EDTMP with 153Sm-EDTMP on an equidose basis in patients with painful skeletal metastases," Journal of Nuclear Medicine, vol. 56, no.10, pp. 1513-1519, 2015.
2- Mundy, G.R., "Metastasis to bone: causes, consequences and therapeutic opportunities," Nature Reviews Cancer, vol. 2, no. 8, pp. 584-593, 2002.
3- Florencio-Silva, R. et al., "Biology of bone tissue: structure, function, and factors that influence bone cells," BioMed research international, Article ID 421746, 2015.
4- Coleman, R.E., "Clinical features of metastatic bone disease and risk of skeletal morbidity," Clinical cancer research, vol. 12, no. 20, pp. 6243s-6249s, 2006.
5- Costa, L. and P.P. Major, "Effect of bisphosphonates on pain and quality of life in patients with bone metastases," Nature Reviews Clinical Oncology, vol. 6, no. 3, pp. 163-174, 2009.
6- Selvaggi, G. and G.V. Scagliotti, "Management of bone metastases in cancer: a review", Critical reviews in oncology/hematology, vol. 56, no. 3, pp. 365-378, 2005.
7- Tsuzuki, S., et al., "Skeletal complications in cancer patients with bone metastases," International Journal of Urology, vol. 23, no. 10, pp. 825-832, 2016.
8- Dennis, K., et al., "Management of bone metastases: recent advances and current status," Journal of Radiation Oncology, vol. 1, no. 3, pp. 201-210, 2012.
9- Janjan, N., et al., "Therapeutic guidelines for the treatment of bone metastasis: a report from the American College of Radiology Appropriateness Criteria Expert Panel on Radiation Oncology," Journal of palliative medicine, vol. 12, no. 5, pp. 417-426, 2009.
10- Sartor, O., P. Hoskin, and Ø.S. Bruland, "Targeted radio-nuclide therapy of skeletal metastases," Cancer treatment reviews, vol. 39, no. 1, pp. 18-26, 2013.
11- Michael, H.-H., Y.-Y. Tsai, and S.E. Hoffe, "Overview of diagnosis and management of metastatic disease to bone," Cancer Control, vol. 19, no. 2, pp. 84-91, 2012.
12- Lewington, V.J., "Bone-seeking radionuclides for therapy," Journal of nuclear medicine, vol. 46, no. 1 suppl, pp. 38S-47S, 2005.
13- Handkiewicz-Junak, D., et al., "EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides," European journal of nuclear medicine and molecular imaging, vol. 45, no. 5, pp. 846-859, 2018.
14- Paes, F.M. and A.N. Serafini, "Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain," in Seminars in nuclear medicine, vol. 40, no. 2, pp. 49-104, 2010.
15- Hirabayashi, H. and J. Fujisaki, "Bone-specific drug delivery systems, " Clinical pharmacokinetics, vol. 42, no. 15, pp. 1319-1330, 2003.
16- Tomblyn, M., "The role of bone-seeking radionuclides in the palliative treatment of patients with painful osteoblastic skeletal metastases," Cancer Control, vol. 19, no. 2, pp. 137-144, 2012.
17- Lange, R., et al., "Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases," Bone, vol. 91, pp. 159-179, 2016.
18- Body, J.-J., S. Casimiro, and L. Costa, "Targeting bone metastases in prostate cancer: improving clinical outcome," Nature reviews Urology, vol. 12, no. 6, pp. 340, 2015.
19- Parker, C.C., et al., "Three-year safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases from phase 3 randomized alpharadin in symptomatic prostate cancer trial," European urology, vol. 73, no. 3, pp. 427-435, 2018.
20- Johnson, J.C., et al., "Calculation of radiation dose at a bone-to-marrow interface using Monte Carlo modeling techniques (EGS4)," Journal of nuclear medicine: official publication, Society of Nuclear Medicine, vol. 33, no. 4, pp. 623-628, 1992.
21- Strigari, L., et al., "Radiopharmaceutical therapy of bone metastases with 89 SrCl 2, 186 Re-HEDP and 153 Sm-EDTMP: a dosimetric study using Monte Carlo simulation," European journal of nuclear medicine and molecular imaging, vol. 34, no. 7, pp. 1031-1038, 2007.
22- Appelbaum, F., et al, "Myelosuppression and mechanism of recovery following administration of 153Samarium-EDTMP," Antibody Imunoconjug Radiopharm, vol. 1, pp. 263-270, 1988.
23- Ranjbar, H., et al, "Dosimetric evaluation of 153Sm-EDTMP, 177Lu-EDTMP and 166Ho-EDTMP for systemic radiation therapy: Influence of type and energy of radiation and half-life of radionuclides," Radiation Physics and Chemistry, vol. 108, pp. 60-64, 2015.
24- Bagheri, R., et al, "Study of bone surface absorbed dose in treatment of bone metastases via selected radiopharmaceuticals: using MCNP4C code and available experimental data," Cancer Biotherapy and Radiopharmaceuticals, vol. 30, no.4, pp. 174-181, 2015.
25- Husmann, O., et al., "Three-dimensional morphology of the proximal femur," The Journal of arthroplasty, vol. 12, no. 4, pp. 444-450, 1997.
26- Giladi, M., et al., "Stress fractures and tibial bone width. A risk factor," The Journal of bone and joint surgery. British volume, vol. 69, no. 2, pp. 326-329, 1987.
27- Bolch, W., et al., "ICRP publication 133: The ICRP computational framework for internal dose assessment for reference adults: specific absorbed fractions," Annals of the ICRP, vol. 45, no. 2, pp. 5-73, 2016.
28- Eckerman, K.F. and A. Endo, MIRD: "radionuclide data and decay schemes," Snmmi, 2007.
29- ICRU, I., "Tissue substitutes in radiation dosimetry and measurement," International Commission on Radiation Units and Measurements, 1989.
30- Tajik-Mansoury, M., H. Rajabi, and H. Mozdarani, "A comparison between track-structure, condensed-history Monte Carlo simulations and MIRD cellular S-values," Physics in Medicine & Biology, vol. 62, no. 5, pp. N90, 2017.
31- Goyal, J. and E.S. Antonarakis, "Bone-targeting radiopharmaceuticals for the treatment of prostate cancer with bone metastases," Cancer letters, vol. 323, no. 2, pp. 135-146, 2012.
32- Pacilio, M., et al., "Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting 223 Ra-dichloride," European journal of nuclear medicine and molecular imaging, vol. 43, no.1, pp. 21-33, 2016.
33- Parker, C., et al., "Alpha emitter radium-223 and survival in metastatic prostate cancer," New England Journal of Medicine, vol. 369, no. 3, pp. 213-223, 2013.
34- Harrison, M.R., et al., "Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease," Cancer management and research, vol. 5, pp. 1, 2013.
35- Sharma, S., et al., "Comparative therapeutic efficacy of 153Sm-EDTMP and 177Lu-EDTMP for bone pain palliation in patients with skeletal metastases: patients’ pain score analysis and personalized dosimetry," Frontiers in medicine, vol. 4, pp. 46, 2017.
36- Thapa, P., et al., "Clinical efficacy and safety comparison of 177Lu-EDTMP with 153Sm-EDTMP on an equidose basis in patients with painful skeletal metastases," Journal of Nuclear Medicine, vol. 56, no.10, pp. 1513-1519, 2015.
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| Issue | Vol 7 No 2 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/fbt.v7i2.3854 | |
| Keywords | ||
| Dosimetry Bone Metastasis Radiopharmaceutical Therapy Monte Carlo Simulation | ||
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How to Cite
1.
Dalvand S, Rajabi H, Omidi A, Malekzadeh E. Dosimetry of Bone-Seeking Radiopharmaceuticals for Palliative Therapy of Bone Metastases: A Simulation Study Using GATE Monte Carlo Code. Frontiers Biomed Technol. 2020;7(2):92-99.
