Development of a freeze-dried radiopharmaceutical kit for dopamine transporters imaging

Document Type : Original Article


Radiation Application Research School, Nuclear Science and Technology Research Institute, Atomic Energy Organization of Iran, Tehran, Iran


Introduction: 99mTc-TRODAT-1 is a promising new radiopharmaceutical with the potential for routine use as the radiopharmaceutical for dopamine transporters scintigraphy as far as its image quality and daily availability are concerned. Here we describe the development of a freeze-dried kit formulation based on the tricine exchange labeling approach for the preparation of this radiopharmaceutical in a clinical setting.
Methods: A freeze-dried formulation contained of TRODAT-1, tricine, SnCl2 and manitol was prepared. Labeling was performed by addition of 1480 MBq 99mTc sodium pertechnetate in a total volume of 2 mL and incubation for 15 min in a boiling water bath. Radiochemical analysis involved ITLC and HPLC methods. The stability of radioconjugate was checked in the presence of human serum at 37 °C up to 24 h.
Results: 99mTc-TRODAT-1 was prepared with a radiochemical purity of >95% and a high stability up to 24 h of the final preparation, and retained biological activity.

Conclusion: The developed kit formulation forms the basis for further clinical evaluation of this promising new radiopharmaceutical.


Main Subjects

Kaufman MJ, Madras BK. Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's-diseased striatum. Synapse. 1991 Sep;9(1):43-9.
Allard P, Alafuzoff I, Carlsson A, Eriksson K, Ericson E, Gottfries CG, Marcusson JO. Loss of dopamine uptake sites labeled with [3H]GBR-12935 in Alzheimer's disease. Eur Neurol. 1990;30(4):181-5.
Frost JJ, Rosier AJ, Reich SG, Smith JS, Ehlers MD, Snyder SH, Ravert HT, Dannals RF. Positron emission tomographic imaging of the dopamine transporter with 11C-WIN 35,428 reveals marked declines in mild Parkinson's disease. Ann Neurol. 1993 Sep;34(3):423-31.
Seibyl JP, Marek KL, Quinlan D, Sheff K, Zoghbi S, Zea-Ponce Y, Baldwin RM, Fussell B, Smith EO, Charney DS, van Dyck C. Decreased single-photon emission computed tomographic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson's disease. Ann Neurol. 1995 Oct;38(4):589-98.
Jurisson S, Berning D, Jia W, Ma D. Coordination compounds in nuclear medicine. Chem. Rev. 1993;93(3):1137-56.
Kung HF, Kim HJ, Kung MP, Meegalla SK, Plössl K, Lee HK. Imaging of dopamine transporters in humans with technetium-99m TRODAT-1. Eur J Nucl Med. 1996 Nov;23(11):1527-30.
Tzen KY, Lu CS, Yen TC, Wey SP, Ting G. Differential diagnosis of Parkinson's disease and vascular parkinsonism by (99m)Tc-TRODAT-1. J Nucl Med. 2001 Mar;42(3):408-13.
Madras BK, Jones AG, Mahmood A, Zimmerman RE, Garada B, Holman BL, Davison A, Blundell P, Meltzer PC. Technepine: a high-affinity 99m-technetium probe to label the dopamine transporter in brain by SPECT imaging. Synapse. 1996 Mar;22(3):239-46.
Kung MP, Stevenson DA, Plössl K, Meegalla SK, Beckwith A, Essman WD, Mu M, Lucki I, Kung HF. [99mTc]TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent. Eur J Nucl Med. 1997 Apr;24(4):372-80.
Choi SR, Kung MP, Plössl K, Meegalla S, Kung HF. An improved kit formulation of a dopamine transporter imaging agent: [Tc-99m]TRODAT-1. Nucl Med Biol. 1999 May;26(4):461-6.
Toth G, Szakonyi Z, Kanyo B, Fulop F, Jancso G, Pavics L. Preparation of [99mTc]TRODAT-1 involving a simple purification method. J Label Compd Radiopharm. 2003;46:1067-73.
Erfani M, Shafiei M. Preparation of 99mTc-TRODAT-1 with high labeling yield in boiling water bath: a new formulation. Nucl Med Biol. 2014 Apr;41(4):317-21.
von Guggenberg E, Sarg B, Lindner H, Alafort LM, Mather SJ, Moncayo R, Decristoforo C. Preparation via coligand exchange and characterization of [99mTc-EDDA-HYNIC-D-Phe1,Tyr3]Octreotide (99mTc–EDDA/HYNIC–TOC). J Label Compd Radiopharm. 2003;46(4):307-18.
Gandomkar M, Najafi R, Shafiei M, Mazidi M, Ebrahimi SE. Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors. Nucl Med Biol. 2007 Aug;34(6):651-7.
Shirmardi SP, Gandomkar M, Maragheh MG, Shamsaei M. Preclinical evaluation of a new bombesin analog for imaging of gastrin-releasing peptide receptors. Cancer Biother Radiopharm. 2011 Jun;26(3):309-16.
Erfani M, Shafiei M, Mazidi M, Goudarzi M. Preparation and biological evaluation of [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide for somatostatin receptor-positive tumor imaging. Cancer Biother Radiopharm. 2013 Apr;28(3):240-7.
Sadeghzadeh N, Gandomkar M, Najafi R, Shafiei M, Sadat Ebrahimi SE, Shafiee A, Larijani B. Preparation and evaluation of a new 99mTc labeled bombesin derivative for tumor imaging. J Radioanal Nucl Chem. 2010;283:181-87.
Shirmardi SP, Gandomkar M, Mazidi M, Shafiei M, Ghannadi Maragheh M Synthesis and evaluation of a new bombesin analog labeled with 99mTc as a GRP receptor imaging agent. J Radioanal Nucl Chem. 2011;288:327-35.
Meegalla SK, Plössl K, Kung MP, Chumpradit S, Stevenson DA, Kushner SA, McElgin WT, Mozley PD, Kung HF. Synthesis and characterization of technetium-99m-labeled tropanes as dopamine transporter-imaging agents. J Med Chem. 1997 Jan 3;40(1):9-17.