Absorbed Dose Estimation of 68Ga-EDTMP in Human Organs

Authors: S. Zolghadri, H. Yousefnia, A. R. Jalilian

Abstract:

Bone metastases are observed in a wide range of cancers leading to intolerable pain. While early detection can help the physicians in the decision of the type of treatment, various radiopharmaceuticals using phosphonates like ⁶⁸Ga-EDTMP have been developed. In this work, due to the importance of absorbed dose, human absorbed dose of this new agent was calculated for the first time based on biodistribution data in Wild-type rats. ⁶⁸Ga was obtained from ⁶⁸Ge/⁶⁸Ga generator with radionuclidic purity and radiochemical purity of higher than 99%. The radiolabeled complex was prepared in the optimized conditions. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography (ITLC) method using Whatman No. 2 paper and saline. The results indicated the radiochemical purity of higher than 99%. The radiolabelled complex was injected into the Wild-type rats and its biodistribution was studied up to 120 min. As expected, major accumulation was observed in the bone. Absorbed dose of each human organ was calculated based on biodistribution in the rats using RADAR method. Bone surface and bone marrow with 0.112 and 0.053 mSv/MBq, respectively, received the highest absorbed dose. According to these results, the radiolabeled complex is a suitable and safe option for PET bone imaging.

Keywords: Absorbed dose, EDTMP, 68Ga, rats.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.3593156

References:

[1] M. G. Agarwal and P. Nayak, “Management of skeletal metastases: An orthopaedic surgeon's guide” Indian J Orthop, vol. 49, pp. 83-100, 2015.
[2] https://radiopaedia.org/articles/skeletal-metastasis-1. Accessed on: 19/09/2017
[3] D. W. Kufe, R. E. Pollock, R. R. Weichselbaum, R. C. Bast, T. S. Gansler, J. F. Holland, et al. Holland-Frei Cancer Medicine. 6th ed. Hamilton (ON): BC Decker, 2003.
[4] H. Yousefnia, S. Zolghadri, H. R. Sadeghi, M. Naderi, A. R. Jalilian and S. Shanesazzadeh, “Preparation and biological assessment of 177Lu-BPAMD as a high potential agent for bone pain palliation therapy: comparison with 177Lu-EDTMP” J. Radioanl Nucl Chem, vol. 307, pp. 1243-1251, 2016.
[5] Lipton, “Pathophysiology of Bone Metastases: How This Knowledge May Lead to Therapeutic Intervention” J Support Oncol, vol. 2, pp. 205-220, 2004.
[6] H. Yousefnia, S. Zolghadri and A. R. Jalilian, “Preparation and biodistribution assessm ent of 111In-BPAMD as a novel agent for bone SPECT imagin” J Radiochim Acta, vol. 103, pp. 653-661, 2015.103(9); p. 653-661Radiochimica Acta; ISSN 0033-8230; CODEN RAACAP; v. 103(9); p. 653-661Radiochimica Acta; ISSN 0033-8230; CODEN RAACAP; v. 103(9); p. 653-661Radiochimica Acta; ISSN 0033-8230; CODEN RAACAP; v. 103(9); p. 653-661 Radiochimica Acta; ISSN 0033-8230; CODEN RAACAP; v. 103(9); p. 653-661 Radiochimica Acta; ISSN 0033-8230; CODEN RAACAP; v. 103(9); p. 653-661.
[7] S. Nilegaonkar, S.Sonar, A. Ranade, and M. Khadilkar, “TC99m MDP bone scan in evaluation of painful scoliosis” Indian J Nucl Med, vol. 25, pp. 67–69, 2010.
[8] D. Cheng, Y. Wang, X. Liu, P. H.Pretorius, M. Liang, M. Rusckowski, and D. J. Hnatowich, “A comparison of 18F PET and 99mTc SPECT imaging in phantoms and in tumored mice” Bioconjug Chem, vol. 21, pp. 1565–1570, 2010.
[9] B. Koolen , E. Vegt , E. J. Rutgers , W. V. Vogel, M. P. Stokkel , C. A. Hoefnagel , A. Fioole-Bruining , M. J. Vrancken Peeters and R. A. Valdés Olmos , “FDG-avid sclerotic bone metastases in breast cancer patients: a PET/CT case series” Ann Nucl Med, vol. 26, pp. 86-91, 2012.
[10] T. Uematsu , S. Yuen , S. Yukisawa , T. Aramaki , N. Morimoto , M. Endo, H. Furukawa , Y. Uchida and J. Watanabe, “ Comparison of FDG PET and SPECT for detection of bone metastases in breast cancer” AJR Am J Roentgenol, vol. 184, pp1266-1273, 2005.M. Costelloe, H.H. Chuang and J. E. Madewell, “FDG PET for the detection of bone metastases: sensivity, specificity and comparison with other imaging modalities: PET Clin, vol. 5, pp. 281-295, 2010.
[12] Colleen M. Costelloe Search for articles by this author Affiliations Division of Diagnostic Imaging, Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA Correspondence Search for articles by this author Affiliations Division of Diagnostic Imaging, Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
[13] Shetty, Y. S. Lee, and J. M. Jeong, “68Ga-Labeled Radiopharmaceuticals for Positron Emission Tomography” Nucl Med Mol Imaging, vol.44, pp. 233–240, 2010.
[14] R. C. Walker, G. T. Smith, E. Liu, B. Moore, J. Clanton and M. Stabin, “Measured Human Dosimetry of 68Ga-DOTATATE” J Nucl Med, vol. 54, pp. 855–860, 2013.
[15] I. Velikyan, “Prospective of 68Ga-Radiopharmaceutical Development” Theranostics, vol. 4, pp. 47-80, 2014.
[16] B. Ramaswamy and C. L. shapiro,“Bisphosphonates in the Prevention and Treatment of Bone Metastases” Available at: http://www.cancernetwork.com/bone-metastases/bisphosphonates-prevention-and-treatment-bone-metastases.Accesses on: 01/09/2003
[17] Holen and R. E. Coleman, “ Bisphosphonates as treatment of bone metastases” Curr Pharm Des, vol. 16, pp. 1262-1271, 2010.
[18] N. Pfannkuchen, M. Meckel, R. Bergmann, M. Bachmann,C. Bal, M. Sathekge, W. Mohnike, R. P. Baum and F. Rösch, “Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases” Pharmaceuticals, vol. 10, 2017.
[19] M. Fellner , R. P. Baum, V. Kubícek, P. Hermann , I. Lukes ,V. Prasad and F. Rösch , “PET/CT imaging of osteoblastic bone metastases with (68)Ga-bisphosphonates: first human study” Eur J Nucl Med Mol Imaging, vol. 37, pp. 834, 2010.
[20] Rabie, R. Enayati, H. Yousefnia, A. R, Jalilian, M. Shamsaei, S. Zolghadri, A. Bahrami-samani and M. Hosntalab, “Preparation, quality control and biodistribution assessment of ¹⁵³Sm-BPAMD as a novel agent for bone pain palliation therapy”Ann Nucl Med, vol. 29, pp. 870-876, 2015.
[21] H. Iagaru, E. Mittra, P. M. Colletti and H. Jadvar, “Bone-Targeted Imaging and Radionuclide Therapy in Prostate Cancer” J Nucl Med, vol. 57, pp. 19-24, 2016.
[22] Mirzaei , A. R. Jalilian, A. Badbarin, M. Mazidi, F. Mirshojaei, P. Geramifar and D. Beiki, “ Optimized production and quality control of (68)Ga-EDTMP for small clinical trials” Ann Nucl Med, vol. 29, pp. 506-511, 2015.
[23] Sparks RB, Aydogan B. Comparison of the effectiveness of some common animal data scaling techniques in estimating human radiation dose. Sixth International Radiopharmaceutical Dosimetry Symposium, Oak Ridge, TN: Oak Ridge Associated Universities; pp. 705–716, 1996.
[24] M. G. Stabin and J. A. Siegel. “Physical Models and Dose Factors for Use in Internal Dose Assessment” Health Phys, vol. 85, pp. 294-310, 2003.