Estimation of Human Absorbed Dose Using Compartmental Model
Dosimetry is an indispensable and precious factor in patient treatment planning to minimize the absorbed dose in vital tissues. In this study, compartmental model was used in order to estimate the human absorbed dose of 177Lu-DOTATOC from the biodistribution data in wild type rats. For this purpose, 177Lu-DOTATOC was prepared under optimized conditions and its biodistribution was studied in male Syrian rats up to 168 h. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. Dosimetric estimation of the complex was performed using radiation absorbed dose assessment resource (RADAR). The biodistribution data showed high accumulation in the adrenal and pancreas as the major expression sites for somatostatin receptor (SSTR). While kidneys as the major route of excretion receive 0.037 mSv/MBq, pancreas and adrenal also obtain 0.039 and 0.028 mSv/MBq. Due to the usage of this method, the points of accumulated activity data were enhanced, and further information of tissues uptake was collected that it will be followed by high (or improved) precision in dosimetric calculations.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1317236Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 406
 L. Bodei, J. Mueller-Brand, R. P. Baum, M. E. Pavel, D. Hörsch, M. S. O'Dorisio, T. M. O'Dorisio, J. R. Howe, M. Cremonesi, D. J. Kwekkeboom and J. J. Zaknun, “The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours.” Eur J Nucl Med Mol Imaging, Vol. 40, pp. 800-816, 2013.
 A. K. Pfeifer, T. Gregersen, H. Grønbæk, C. P. Hansen, J. Müller-Brand, K. Herskind Bruun, K. Krogh, A. Kjær and U. Knigge, “Peptide Receptor Radionuclide Therapy with 90Y-DOTATOC and 177Lu-DOTATOC in Advanced Neuroendocrine Tumors: Results from a Danish Cohort Treated in Switzerland.” Neuroendocrinology, vol. 93, pp.189–196, 2011.
 D. Kwekkeboom, Krenning EP and de Jong M, “Peptide receptor imaging and therapy” J Nucl Med, vol. 41, pp. 1704–1713, 2000.
 S. Koukouraki, L. G. Strauss, V. Georgoulias, J. Schuhmacher, U. Haberkorn, N. Karkavitsas and A. Dimitrakopoulou-Strauss, “Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy.” Eur J Nucl Med Mol Imaging, vol. 33, pp. 460–466, 2006.
 L. Bodei, M. Cremonesi, S. Zoboli, C. Grana, M. Bartolomei, P. Rocca, M. Caracciolo, H. R. Mäcke, M. Chinol and G. Paganelli, “Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase 1 study.” Eur J Nucl Med, vol. 30, pp. 207–216, 2003.
 R. P. Baum, A. W. Kluge, H.Kulkarni, U. Schorr-Neufing, K. Niepsch, N. Bitterlich and C. J. A. van Echteld, “(177Lu-DOTA)0-D-Phe1-Tyr3-Octreotide (177Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study” Theranostics, vol. 6, pp. 501-510, 2016.
 C. Dong, Z. Liu and F. Wang .”Peptide-based Radiopharmaceuticals for Targeted Tumor Therapy.” Curr Med Chem, vol. 21, pp.139–152, 2014.
 M. Cremonesi, M. Ferrari, L. Bodei, G. Tosi and G. Paganelli, “Dosimetry in Peptide Radionuclide Receptor Therapy: A Review” J Nucl Med, vol. 47, pp. 1467-1475, 2006.
 D. M. Foster and R. C. Boston, The use of computers in compartmental analysis: the SAAM and CONSAM programs. Boca Raton: USA, 1983, pp. 73-142.
 R. E. Carson, “Tracer kinetic modeling in PET.” in Positron emission tomography: basic sciences, 2nd ed. D. L. Bailey, D. W. Townsend, P. E. Valk, M. N. Maisey, Eds. London, UK: Springer, 2005, pp. 127–159.
 R. B. Sparks and B. Aydogan, “Comparison of the effectiveness of some common animal data scaling techniques in estimating human radiation dose.” Sixth International Radiopharmaceutical Dosimetry Symposium Oak Ridge; Oak Ridge Associated Universities, pp. 705–716, 1996.
 H. Yousefnia, M. Mousavi-Daramoroudi, S. Zolghadri and F. Abbasi-Davani, “Preparation and biodistribution assessment of low specific activity 177Lu-DOTATOC for optimization studies.” Iran J Nucl Med, vol. 24, pp. 85-91, 2016.
 J. A. Jacquez, Compartmental analysis in biology and medicine. Amsterdam, Holland: Elsevier/North, 1972.
 D. H. Anderson, “Compartmental modeling and tracer kinetics.” New York: Springer-Verlag, pp. 302, 1983.
 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.
 F. Guerriero, M. E. Ferrari, F. Botta, F. Fioroni, E. Grassi, A. Versari, A. Sarnelli, M. Pacilio, E. Amato, L. Strigari, L. Bodei, G. Paganelli, M. Iori, G. Pedroli, and M. Cremonesi, “Kidney Dosimetry in 177Lu and 90Y Peptide Receptor Radionuclide Therapy: Influence of Image Timing, Time-Activity Integration Method, and Risk Factors” Biomed Res Int, 2013:935351.