ISC, CAS, Google Scholar     h-index: 20

Document Type : Original Research Article

Authors

Synthesis and Molecular Simulation Laboratory, Chemistry Department, Pars Isotope Company, P.O. Box: 1437663181, Tehran, Iran

10.33945/SAMI/PCBR.2019.4.4

Abstract

The purpose of this research study is to prepare Exametazime (d,l-HMPAO) kit for labeling with 99m-technetium radionuclide as a brain perfusion diagnostic system. In first step, the active pharmaceutical ingredient d,l-HMPAO was prepared in two steps with the purity of 99.29 %. Its molecular structure was characterized using elemental analysis, Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) technique. In second step, the d,l-HMPAO kit was prepared using six different formulations and labeled by technetium-99m radionuclide. The high radiochemical yield was attributed to the high amount of SnCl2 and adding phosphate buffer. The animal studies were conducted on three-month old male Wistar rats. The biodistribution studies revealed that, the mean activity in brain of all rats was above 1% ID/g. This showed the high isomerism purity of the synthesized compound (d,l-HMPAO) and optimization of the suggested formulations.

Graphical Abstract

Kit formulation of active pharmaceutical ingredient d,l-HMPAO as a brain perfusion diagnostic system

Keywords

Main Subjects

References
[1] L. Uccelli, P. Martini, M. Pasquali and A. Boschi, Radiochemical purity and stability of 99m Tc-HMPAO in routine preparations. Journal of Radioanalytical and Nuclear Chemistry,  314 (2017)  1177-1181.
[2] S.M. Rathmann, Z. Ahmad, S. Slikboer, H.A. Bilton, D.P. Snider and J.F. Valliant, The Radiopharmaceutical Chemistry of Technetium-99m, in Radiopharmaceutical Chemistry. (2019), Springer.  311-333.
[3] J. Pijarowska-Kruszyna, U. Karczmarczyk, A.W. Jaroń, E. Laszuk, M. Radzik, P. Garnuszek and R. Mikołajczak, New synthesis route of active substance d, l-HMPAO for preparation Technetium Tc99m Exametazime. Nuclear Medicine Review,  20 (2017)  88-94.
[4] D. Chroustová, N. El-Lababidi, J. Trnka, L. Černa and L. Lambert, Scintigraphy with 99mTc-HMPAO labeled leukocytes is still an accurate and convenient tool to rule out suspected inflammatory bowel disease in children. Nuclear Medicine Review,  22 (2019)  69-73.
[5] S. Auletta, V. Iodice, F. Galli, N. Lepareur, A. Devillers and A. Signore, Study of Binding Kinetics and Specificity of 99mTc-SSS-Complex and 99mTc-HMPAO to Blood Cells. Contrast media & molecular imaging,  2018 (2018) 
[6] C. Suzuki, S. Kimura, M. Kosugi and Y. Magata, Quantitation of rat cerebral blood flow using 99mTc-HMPAO. Nuclear medicine and biology,  47 (2017)  19-22.
[7] S.M.d.A. Giorgio, M.G. Caprio, F. Galante, G. Russo, A. Romano, E. Vergara, M. Alessio and A. Cuocolo, Clinical Value of Perfusion Abnormalities of Brain on Technetium-99m HMPAO Single-Photon Emission Computed Tomography in Children With Sydenham Chorea. Journal of child neurology,  32 (2017)  316-321.
[8] P. Garrigue, L. Giacomino, C. Bucci, V. Muzio, M.A. Filannino, F. Sabatier, F. Dignat-George, P. Pisano and B. Guillet, Single photon emission computed tomography imaging of cerebral blood flow, blood–brain barrier disruption, and apoptosis time course after focal cerebral ischemia in rats. International Journal of Stroke,  11 (2016)  117-126.
[9] L. Vlerick, K. Peremans, R. Dockx, K. Audenaert, C. Baeken, J.H. Saunders and I. Polis, The long-term effects of single and repeated subanaesthetic ketamine administration on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT. Psychiatry Research: Neuroimaging,  285 (2019)  18-24.
[10] C. Suzuki, M. Kosugi and Y. Magata, Noninvasive quantitation of rat cerebral blood flow using 99m Tc-HMPAO—assessment of input function with dynamic chest planar imaging. EJNMMI research,  8 (2018)  21.
[11] J. Hodler, G.K. von Schulthess and C.L. Zollikofer, Diseases of the brain, head & neck, spine 2012-2015: Diagnostic Imaging and Interventional Techniques. (2012): Springer Science & Business Media.
[12] M. Jacobsen, A. Jensen, G.B. Storvestre, T.M. Bergstrom, M. Rashi, D. Nori, B. Nielssen, P. Wiktor and K.-E. Hymer, Experiences with 99mTc-HMPAO in a diagnostic pathway for violent patients with schizophrenic spectrum disorders. Current radiopharmaceuticals,  10 (2017)  115-122.
[13] J. Li, Y. Yang, Y. Zhu, L. Zhou, Y. Han, T. Yin, Z. Cheng, G. Zhang, Y. Shen and J. Chen, Towards characterizing the regional cerebral perfusion in evaluating the severity of major depression disorder with SPECT/CT. BMC psychiatry,  18 (2018)  70.
[14] J. Wang and R. Carroll, Nuclear Medicine Imaging in Epilepsy. J Epilepsy,  2 (2015)  e105.
[15] V. Mancini, G. Mastria, V. Frantellizzi, P. Troiani, S. Zampatti, S. Carboni, E. Giardina, R. Campopiano, S. Gambardella and F. Turchi, Migrainous Infarction in a Patient With Sporadic Hemiplegic Migraine and Cystic Fibrosis: A 99mTc‐HMPAO Brain SPECT Study. Headache: The Journal of Head and Face Pain,  59 (2019)  253-258.
[16] Z. Al-Faham, M.A. Kassir, D. Wood and H.R. Balon, Appearance of Meningioma on 99mTc-HMPAO SPECT: Correlation with MRI. Journal of nuclear medicine technology,  44 (2016)  90-91.
[17] S.S.H. Davarani, Z. Rezayati-zad, A. Taheri and N. Rahmatian, Highly selective solid phase extraction and preconcentration of Azathioprine with nano-sized imprinted polymer based on multivariate optimization and its trace determination in biological and pharmaceutical samples. Mater Sci Eng C Mater Biol Appl,  71 (2017)  572-583.
[18] O. Solomon, W. Rabiu Saidu Umar, H. Sanusi Wara, A. Sadiq Yakubu, M. Michael Azubuike, M. Asugu Mary and H. Louis, Antiulcerogenic Activity of methanol extract and solvent fractions of Stem Bark of Lannea acida (A. Rich) Against Ethanol-Induced Gastric Mucosal Injury in Albino Rats. Prog. Chem. Biochem. Res.,  1 (2018)  29-39.
[19] F. Welz, J.C. Sanders, T. Kuwert, J. Maler, J. Kornhuber and P. Ritt, Absolute SPECT/CT quantification of cerebral uptake of 99mTc-HMPAO for patients with neurocognitive disorders. Nuklearmedizin,  55 (2016)  158-165.
[20] N. Nikolov, S. Makeyev, O.Y. Yaroshenko, T. Novikova and M. Globa, Quantitative evaluation of the absolute value of the cerebral blood flow according to the scintigraphic studies with 99mTc-HMPAO. Наукові вісті Національного технічного університету України Київський політехнічний інститут, (2017)  61-68.
[21] M. Nabati, Prediction of the structural and spectral properties for L, L-ethylenedicysteine diethylester (EC) and its complex with Technetium-99m radionuclide. Journal of Physical & Theoretical Chemistry,  14 (2017)  49-61.
[22] M. Nabati, V. Bodaghi-Namileh and S. Sarshar, Molecular Modeling of the antagonist compound esketamine and its molecular docking study with non-competitive N-methyl-D-aspartate (NMDA) receptors NR1, NR2A, NR2B and NR2D. Progress in Chemical and Biochemical Research,  2 (2019)  108-119.
 
How to cite this manuscript:
M. Davarpanah, H. Abbasi, M. Nabati, H. Sabahnoo, V. Bodaghi-Namileh, M. Mazidi, H. Movahhed-Tazehkand and H. Mohammadnejad-Mehrabani, Kit formulation of active pharmaceutical ingredient d,l-HMPAO as a brain perfusion diagnostic system. Progress in Chemical and Biochemical Research,  2 (2019)  185-191.
DOI: 10.33945/SAMI/PCBR.2019.4.4