Journal of Radiation Research and Applied Sciences 8 (2015) 317e322. Available online at ScienceDirect

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Journal of Radiation Research and Applied Sciences 8 (2015) 317e322 HOSTED BY Available online at www.sciencedirect.com ScienceDirect Journal of Radiation Research and Applied Sciences journal homepage: http://www.elsevier.com/locate/jrras Estimation of kidney and bladder radionuclide activity for patients undergoing bone scan Luc T. Bambara a, Augustine K. Kyere a, Francis Hasford a,b,*, Edem K. Sosu a,b, Isaac K. Wilson c a School of Nuclear and Allied Sciences, University of Ghana, P.O. Box AE1, Accra, Ghana b Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, P.O. Box LG 80, Accra, Ghana c National Centre for Radiotherapy and Nuclear Medicine, Korle-Bu Teaching Hospital, P.O. Box KB 369, Accra, Ghana article info Article history: Received 6 February 2015 Received in revised form 10 April 2015 Accepted 28 April 2015 Available online 14 May 2015 Keywords: Counts of activity Quantitative assessment Primary bone tumour Scintigraphy Radionuclide abstract Radionuclide activities in the kidney and bladder have been estimated experimentally from practical data 3 h after injection of Tc-99m MDP, using conjugate view methodology. The study involved sixty-five patient images from the database of a nuclear medicine department in Ghana. Timeeactivity curve was stimulated with MatLab computer program using biokinetic model published in MIRD Report 13. The model was used to determine theoretical activities in kidney and bladder, which were compared with the experimental data. Estimated radionuclide activities for the kidney and bladder were both minimal in the experimental case comparative to the theoretical. The fraction of injected activity in kidney and bladder were less than 1% of injected activity, and hence kidney and bladder could be seen to receive very low doses during bone scans. Copyright 2015, The Egyptian Society of Radiation Sciences and Applications. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction Nuclear medicine is a medical specialty using radioisotopes as tracers to diagnose diseases or for therapy. These tracers are usually attached to chemical compounds that are attracted to organs of interest such as bones or thyroid gland. After administration into the body, tracers emit characteristic radiations. Special electronic instruments, such as scintillation detector or a gamma camera, displays the recorded emissions as images. The images yield information about the anatomy or the functional state of the organ being imaged. In clinical applications of nuclear medicine, the amount of administered activity is low such that its corresponding absorbed dose to imaged and non-imaged tissues are typically very low and thus stochastic effect are outweighed by the diagnostic benefit of the imaging process (Bolch & Fahey, 2013). The role of internal dosimetry in diagnostic nuclear medicine is thus to provide the basis for stochastic risk quantification. Once this risk is quantified, it may be used to * Corresponding author. Medical Radiation Physics Centre, Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, P.O. Box LG 80 Legon, Accra, Ghana. E-mail addresses: haspee@yahoo.co.uk, haspee@gmail.com (F. Hasford). Peer review under responsibility of The Egyptian Society of Radiation Sciences and Applications. http://dx.doi.org/10.1016/j.jrras.2015.04.005 1687-8507/Copyright 2015, The Egyptian Society of Radiation Sciences and Applications. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

318 Journal of Radiation Research and Applied Sciences 8 (2015) 317e322 optimize the amount of administered activity in order to maximize image quality while minimizing patient risk. This optimization is considered, and always evaluated for any imaging procedure (IAEA, 2011). Accurate dosimetry of diagnostic procedures is important for making judgments on the diagnostic benefits to the patient compared to the associated radiation risks. Dosimetry of diagnostic radiopharmaceuticals is therefore primarily concerned with the dosimetry of a total population or group (Hickson, 2011). Image quantification in nuclear medicine is used, among other options, to estimate activity in human subjects for the calculation of radiation dose in individuals undergoing radionuclide therapy and to study pharmacokinetics for approval of new radiopharmaceuticals (Pereira, Stabin, Lima, Guimar~aes, & Forrester, 2010; Sgouros et al., 2003). The objective of this study is to determine the amount of radionuclide activity in kidney and bladder of patients 3 h after injection of technetium-99m (Tc-99m) in nuclear medicine, using conjugate view approach. 2. Methodology Single photon emission computed tomography (SPECT) system (Siemens, Germany) was used for performing bone scans on patients as employed in studies by Yigbedeck et al. (2014) and Hasford et al. (2015). The system was equipped with low energy all purpose collimator and whole-body images acquired 3 h post-injection of Tc-99m methylene diphosphonate (MDP). Quantitative analyses were performed on acquired images by drawing regions of interest (ROIs) in the system's e.soft software application, and tabulating counts of radionuclide activity in the bladder and kidneys. Whole-body bone scintigrams of 65 patients acquired with the SPECT system were randomly selected for this study. Computed tomography (CT) scans of 36 of the sampled patients were obtained and used in estimating average thicknesses of the organs of interest and their associated body section. RadiAnt DICOM viewer software was used in measuring the thicknesses in the anterior e posterior direction. Table A1 in Appendix A presents data on sampled patients' age, gender and administered activity. Mean counts of activity in the kidney and bladder were estimated using conjugate view methodology (Hasford et al., 2015; Yigbedeck et al., 2014). Anterior and posterior counts of activity were obtained from the scintigrams and geometric mean count estimated using equation (1). p GMC ¼ ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi C A C P (1) Counts of activity were converted into radionuclide activity (mci) using Equation (2) (Pereira et al., 2010). rffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi C A C P A ¼ f (2) e m et C where, A is organ activity (mci); C A and C P are the anterior and posterior background corrected counts respectively; t is body thickness across organ of interest (anterioreposterior); m e is effective linear attenuation coefficient of Tc-99m in soft tissue; C is system calibration factor in counts per unit activity, expressed as fsource counts=known activityg; f represents correction for the source region attenuation coefficient (m e ) and source organ thickness (t) and is expressed as fðm e x=2þ=sinhðm e x=2þg (J onsson, 2007; Shahbazi-Gahrouei, Cheki, & Moslehi, 2012; Siegel et al., 1999; Stabin, 2008). Biokinetic model in MIRD Report 13 (Weber et al., 1989) was used to simulate transfer of Tc-99m in the body with MatLab program. The transfer of Tc-99m activity in blood, bone, kidney and bladder was simulated by Equation (3)e(6). dq Bd dq B0 dq Kid ¼ ðk R þ K 21 þ k 31 Þq Bd þ k 12 q B0 (3) ¼ ðk R þ K 12 Þq B0 þ k 21 q Bd : (4) ¼ ðk R þ K 43 Þq Kid þ k 31 q Bd (5) dq Ub ¼ k R q UB þ K 43 q Kid (6) Table 1 presents transfer rate constants k 12, k 21, k 31 and k 43 specified in MIRD Report 13. Physical decay constant k R ¼ 0.115 h 1. The resultant MatLab algorithm for the transfer of Tc-99m activity in blood, bone, kidney and bladder is presented in Appendix B: 3. Results and discussion 3.1. Organ and body thickness Estimated average thicknesses of kidney and bladder, and their associated body sections for the 36 patients are summarized in Table 2. The average thickness estimates for left and right kidneys vary insignificantly by 4.2%. The measurements of 4.92 cm and 5.14 cm for the left and right kidneys are respectively consistent with study by Larsson et al. (2012). For 36 patients, the group estimated the thicknesses of left and right kidneys to be 5.39 cm and 5.69 cm respectively. The estimated average thicknesses in this study were used to calculate attenuation coefficient of Tc-99m by conjugate view approach. 3.1.1. Radionuclide activity in kidney and bladder Average estimates for the radionuclide activity in the kidneys and bladder 3 h after injection of Tc-99m MDP, and their respective fractions of injected activity for the 65 patients are presented in Table 3. Radionuclide activity in the kidneys (0.041 ± 0.013 mci) is much lesser than in the bladder Table 1 e Transfer rate constants. Radiopharmaceutical Tc-99m MDP k 12 0.063 ± 0.010 k 21 0.295 ± 0.025 k 31 0.305 ± 0.012 k 43 3.25 ± 0.37

Journal of Radiation Research and Applied Sciences 8 (2015) 317e322 319 Table 2 e Average thicknesses of organs and body section from CT scans. Table 4 e Theoretically estimated radionuclide activity in kidney and bladder. Ant/Post thickness (mm) Organ 3 h Post injection of Tc-99m MDP Organ Body section Left Kidney 49.23 ± 6.37 207.86 ± 34.26 Right Kidney 51.38 ± 5.66 207.97 ± 35.12 Bladder 37.19 ± 4.63 203.88 ± 40.12 Theoretically estimated activity (mci) Fraction of injected activity Kidney 0.270 1.5% Bladder 5.276 29.31% Table 3 e Experimentally estimated radionuclide activity in kidneys and bladder. Organ Average activity (mci) (0.132 ± 0.084 mci) 3 h post injection. Fraction of injected activity estimated in kidney and bladder at 3 h post injection are 0.22% and 0.72% respectively. The injection of Tc-99m MDP intravenously is mainly excreted in the form of urine through the urinary system, of which kidney and bladder form part. Kidney plays the role of blood filter and the bladder serves a temporary storage reservoir for urine. Relatively high activity recorded in bladder could be a result of the collection of large quantity of urine which is subsequently eliminated through the genitals. 3.2. Time-activity curve Fraction of injected activity Left Kidney 0.041 ± 0.013 0.22% Right 0.041 ± 0.012 0.22% Kidney Bladder 0.132 ± 0.084 0.72% (3)e(6) and presented in Fig. 1. Blood recorded significant maximum radionuclide activity of 16.8 mci at 0.1 h (6 min) post injection of Tc-99m MDP. This results because the radionuclide is directly injected into the blood stream where emission of gamma rays begins to occur before the radionuclide reaches the bone, kidney and bladder. The activity curve of blood decays with increasing time before Tc-99m begins to emit gamma rays in the bone, kidney and bladder. Due to the fact that the bladder acts as a reservoir for urine storage, Tc- 99m MDP stays in the bladder for a long period of time. The bladder stores urine for approximately 6 h, thereby accounting for its highest activity of 5.35 mci over kidney's activity of 1.08 mci at 1 h post injection and bone's activity of 4.78 mci at 4.3 h post injection. Theoretically estimated radionuclide activity in kidney and bladder 3 h after injection of Tc-99m MDP and their corresponding fraction of injected activity are presented in Table 4. High fraction of injected activity (29.31%) remains in the bladder 3 h after injection. 3.3. Comparison of experimental and theoretical radionuclide activities Theoretically, timeeactivity curve for this study was obtained from MatLab stimulation of the biokinetic model published in MIRD Report 13. The resultant MatLab algorithm is presented in Appendix B. Plotted curves representing blood, bone, kidney and bladder activities were generated from Equation Theoretically estimated radionuclide activities from stimulation were considered as highest limit of activity for the organs of interest in this study. Table 5 shows the experimentally and theoretically estimated average radionuclide activities 3 h after injection of Tc-99m MDP. Comparison of radionuclide Fig. 1 e Time activity curve for Tc-99m MDP for blood, bone, kidney and bladder.

320 Journal of Radiation Research and Applied Sciences 8 (2015) 317e322 Table 5 e Experimental and theoretical activity for kidney and bladder. Organs 3 h Post injection of Tc-99m MDP Activity (mci) Fraction of injected activity (%) Experimental Theoretical Experimental Theoretical Kidney 0.041 0.270 0.22 1.5 Bladder 0.132 5.276 0.72 29.31 activities depicts that the experimental estimates are comparatively smaller than the theoretical estimates. Less than 1% of the administered activity remained in the kidneys and bladder 3 h after injection of Tc-99m MDP. The theoretically estimated activity from simulation of MIRD biokinetic model is considered as maximum limit in the organs of interest because the model does not consider the transfer rate from the bladder until urination. Due to this, high activity estimates are observed 3 h after injection in the theoretical case. Given that the simulated estimates are upper limiting values, patients undergoing bone scan in this study may be considered safe because of the low radionuclide activities recorded in the kidney and bladder. 4. Conclusion Estimation of radionuclide activities in kidney and bladder are considered necessary due the associated organ doses and risk of cancer induction through late effects. Experimental and theoretical estimates of activity show that kidney and bladder, which are critical organs, each receive less than 1% fraction of injected activity during nuclear medicine bone scans. The fractions give indication that absorbed dose to the two organs are typically very low and thus stochastic risks of cancer induction may be greatly outweighed by diagnostic benefit of the imaging procedure. 5. Conflict of interest No conflict of interest. Acknowledgement The study was performed at a nuclear medicine unit in Ghana. The authors acknowledge with gratitude the support from the department. Appendix A Table A1 e Bio data and injected activity of reported patient. Patient ID Age (yrs) Gender Injected activity (mci) 1 56 M 19.5 2 68 M 17.4 3 60 M 17.9 4 56 M 18.0 5 55 M 19.2 6 37 F 17.9 7 67 M 17.3 8 70 M 18.3 9 65 M 16.8 10 71 F 18.8 11 62 M 16.1 12 61 M 17.2 13 66 M 15.5 14 59 F 15.8 15 73 M 15.3 16 73 M 16.7 17 58 F 15.4 18 63 F 18.5 19 80 M 16.5 20 66 F 20.8 21 83 M 20.0 22 68 M 23.5 23 71 F 20.7 24 64 F 21.1 25 50 F 24.7 26 59 M 20.8 27 86 M 20.7 28 66 M 24.5 29 73 M 22.5 30 60 M 21.2 31 63 F 20.6 32 78 M 22.7 33 61 F 22.0 34 57 M 23.1 35 58 M 20.7 36 62 M 21.3 37 41 F 22.6 38 36 F 13.4 39 65 M 14.9 40 37 F 19.0 41 67 M 16.1 42 54 F 14.1 43 74 M 15.9 44 38 F 11.5 45 25 F 12.5 46 63 M 13.4 47 60 M 19.1 48 45 F 17.6

Journal of Radiation Research and Applied Sciences 8 (2015) 317e322 321 Table A1 e (continued) Patient ID Age (yrs) Gender Injected activity (mci) 49 49 F 16.8 50 73 M 21.2 51 58 M 25.2 52 50 F 21.7 53 63 F 10.2 54 68 M 10.6 55 75 M 19.9 56 63 F 19.7 57 66 M 18.4 58 82 M 22.8 59 40 F 17.2 60 76 M 18.5 61 87 F 18.8 62 60 M 18.2 63 71 F 18.2 64 72 F 14.1 65 47 M 14.2 Appendix B MatLab algorithm for the transfer of Tc-99m activity in blood, bone, kidney and bladder. references Bolch, W., & Fahey, F. (2013). The management of imaging procedure dose. Nuclear Medicine, 2. https://www.aapm.org/ meetings/2013am/prabs.asp?mid¼77&aid¼22648. Hasford, F., Yigbedeck, Y. H., Kyere, A. K., Wilson, I. K., Ankrah, A. O., & Sosu, E. K. (2015). Quantification of radionuclide uptake levels for primary bone tumors. Journal of Radiation Research and Applied Sciences, 8(1), 182e189. Hickson, K. J. (2011). Internal radionuclide dosimetry of model and patient based voxelised phantoms using the GATE toolkit. Master's

322 Journal of Radiation Research and Applied Sciences 8 (2015) 317e322 thesis submitted to school of applied Sciences (p. 179). Australia: University Melbourne. International Atomic Energy Agency. (2011). Report of a consultancy meeting held 26e28 september 2011. Vienna: IAEA. J onsson, L. (2007). Internal dosimetry: development and evaluation of methods and models. PhD thesis submitted to faculty of science. Sweden.: Lund University, ISBN 978-91- 628-7090-4. Larsson, M., Bernhar, P., Svensson, J. B., Wangberg, B., Ahlman, H., & Forssell-Aronsson, E. (2012). Estimation of absorbed dose to the kidneys in patients after treatment with Lu-177 octreotate: comparison between methods based on planar scintigraphy. EJNMI Research, 2, 49. Pereira, J. M., Stabin, M. G., Lima, F. R. A., Guimar~aes, M. I. C. C., & Forrester, J. W. (2010). Image quantification for radiation dose calculations limitations and uncertainties. Health Physics, 99(5), 688e701. Sgouros, G., Squeri, S., Ballangrud, A. M., Kolbert, K. S., Teitcher, J. B., Panageas, K. S., et al. (2003). Patient-specific, 3- dimensional dosimetry in non-hodgkin's lymphoma patients treated with 131 I-anti-B1 antibody: assessment of tumour dose-response. Journal of Nuclear Medicine, 44(2), 260e268. Shahbazi-Gahrouei, D., Cheki, M., & Moslehi, M. (2012). Estimation of organ absorbed doses in patients from 99mTcdiphosphonate using the data of MIRDose software. Journal of Medical Signaals and Sensors, 2, 231e234. Siegel, J. A., Thomas, S. R., Stubbs, J. B., Stabin, M. G., Hays, M. T., Koral, K. F., et al. (1999). MIRD pamphlet No. 16:techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimate. Journal of Nuclear Medicine, 4037Se4061S. Stabin, M. G. (2008). The importance of patient-specific dose calculations in nuclear medicine. Nuclear Engineering and Technology, 40(7). Weber, D. A., Makler, P. T., Watson, E. E., Coffey, J. L., Thomas, S. R., & London, J. (1989). MIRD dose estimate report no 13: radiation absorbed dose from technetium-99m-labeled bone imaging agents. Journal of Nuclear Medicine, 30, 1117e1122. Yigbedeck, Y. H., Kyere, A. K., Wilson, I. K., Hasford, F., Sosu, E. K., & Ankrah, A. O. (2014). Comparative study of radionuclide uptake levels between primary and metastatic bone tumors. World Journal of Nuclear Medicine, 13, 50e55.