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Current Status and Prospects of 99mTc-radiopharmaceuticals |
TIAN Jiale;JIA Hongmei |
Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China |
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Abstract Using molecular imaging techniques, radionuclide-labeled molecular probes can provide noninvasive and real-time visualization of specific biochemical processes in the living humans and pathological process of various human diseases at the molecular level, which will pave the way to precision medicine. 99mTc-radiopharmaceuticals is playing significant roles in the diagnosis of human diseases and efficacy monitoring of therapeutic strategies together with single photon emission computed tomography imaging modality. This review provided an overview of current status of 99mTc-radiopharmaceuticals used in clinic and clinical trials. Possible future trends in the field of 99mTc-radiopharmaceuticals were discussed. Investigation on the new targets or new biochemical processes as targets and basic technetium chemistry including exploring novel labeling methods and novel technetium building blocks were addressed. Development on the novel 99mTc-radiopharmaceuticals with high affinity, selectivity and specificity for the imaging of unique targets or specific biochemical processes together with 99mTc-labeling methods suitable for clinical use will accelerate the clinical translation of new 99mTc-radiopharmaceuticals.
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|
[1] |
http:∥www.world-nuclear.org/information-library/non-power-nuclear-applications/radiois-otopesresearch/radioisotopes-in-medicine.aspx, Updated December 2017[M].
|
[2] |
中华医学会核医学分会. 2016年全国核医学现状普查结果简报[J]. 中华核医学与分子影像杂志,2016,(5):479-480.Chinese Society of Nuclear Medicine. A brief report on the results of the national survey of nuclear medicine in 2016[J]. Chinese Journal of Nuclear Medicine and Molecular Imaging, 2016, 5: 479-480(in Chinese).
|
[3] |
Jurisson S S, Lydon J D. Potential technetium Small molecule radiopharmaceuticals[J]. Chem Rev, 1999, 99(9): 2205-2218.
|
[4] |
Juergens S, Herrmann W A, Kuehn F E. Rhenium and technetium based radiopharmaceuticals: Development and recent advances[J]. Journal of Organometallic Chemistry, 2014, 751: 83-89.
|
[5] |
Vera D R, Wallace A M, Hoh C K, et al. A synthetic macromolecule for sentinel node detection: 99mTc-DTPA-mannosyl-dextran[J]. J Nucl Med, 2001, 42(6): 951-959.
|
[6] |
International Atomic Energy Agency, Radiopharmaceuticals for Sentinel lymph node detection: status and trends[C]. Vienna: International Atomic Energy Agency, 2015.
|
[7] |
张现忠,杨文江,王学斌,等. 一种用于制备锝-99m标记的GSA的药盒及其制备方法:中国,CN200810057222.1[P]. 2008-01-30.
|
[8] |
Molecular Insight Pharmaceuticals, Inc. Study to Evaluate 99mTc-MIP-1404 SPECT/CT Imaging in Men With Biopsy Proven Low-Grade Prostate Cancer (prospect-AS)[DB]. ClinicalTrials.gov Identifier: NCT02615067, 2018.
|
[9] |
Cyclomedica Australia PTY Limited. A Comparison of technegas and Xenon-133 planar lung imaging in subjects referred for ventilation scintigraphy[DB]. ClinicalTrials.gov Identifier: NCT03054870, 2018.
|
[10] |
Universidade Federal do Rio de Janeiro.99mTc-anti-TNF-alpha scintigraphy in the evaluation of inflammatory processes activity[DB]. ClinicalTrials.gov Identifier: NCT02134613, 2016.
|
[11] |
Advanced Accelerator Applications.99mTc-rhAnnexin V-128 in diagnosis of spondyloarthritis[DB]. ClinicalTrials.gov Identifier: NCT03232580, 2017.
|
[12] |
Advanced Accelerator Applications.99mTc-rhAnnexin V-128 imaging and cardiotoxicity in Patients with early breast cancer[DB]. Clinical Trials.gov Identifier: NCT02677714, 2017.
|
[13] |
Institut National de la Santé Et de la Recherche Médicale, France. Assessment of radiolabeled rhAnnexin V-128 in infective endocarditis (AnnIE)[DB]. ClinicalTrials.gov Identifier: NCT02459613, 2016.
|
[14] |
Advanced Accelerator Applications.99mTc-rhAnnexin V-128 imaging for carotid atherosclerosis[DB]. ClinicalTrials.gov Identifier: NCT02667457, 2018.
|
[15] |
Assistance Publique -Hpitaux de Paris. Study of tolerance, biodistribution and dosimetry of fucoidan radiolabeled by technetium-99m (NANO-ATHERO)[DB]. ClinicalTrials.gov Identifier: NCT03422055, 2018.
|
[16] |
Cell>Point LLC. Efficacy and saftey study of99mTc-ECDG in the evaluation of coronary artery disease (CAD)[DB]. ClinicalTrials.gov Identifier: NCT01899833, 2017.
|
[17] |
Cell>Point LLC. A Phase 3 Study of99mTc-EC-DG SPECT/CT Versus PET/CT in Lung Cancer[DB]. ClinicalTrials.gov Identifier: NCT01394679, 2017.
|
[18] |
University of Chicago. Feasibility of Imaging in the treatment of patients with advanced head and neck cancer[DB]. ClinicalTrials.gov Identifier: NCT01359267, 2017.
|
[19] |
Wolfson Medical Center. Trodat 1 SPECT and dopamine polymorphism[DB]. ClinicalTrials.gov Identifier: NCT01381302, 2016.
|
[20] |
Peking Union Medical College Hospital.99mTc-3PRGD2 SPECT/CT in lung cancer patients (TcRGDLC)[DB]. ClinicalTrials.gov Identifier: NCT01737112, 2017.
|
[21] |
First Affiliated Hospital of Fujian Medical University.99mTc-3PRGD2 SPECT/CT in breast cancer patients[DB]. ClinicalTrials.gov Identifier: NCT02742168, 2016.
|
[22] |
First Affiliated Hospital of Fujian Medical university.99mTc-3PRGD2 SPECT/CT in esophagus cancer patients[DB]. ClinicalTrials.gov Identifier: NCT02744729, 2016.
|
[23] |
First Affiliated Hospital of Fujian Medical University.99mTc-3PRGD2 SPECT/CT in rheumatoid arthritis patients (TRGDRA)[DB]. ClinicalTrials.gov Identifier: NCT02723760, 2016.
|
[24] |
Michael O’Connor. Detection of Aggressive Breast Tumors Using Tc-99m-NC100692[DB]. ClinicalTrials.gov Identifier: NCT00888589, 2014.
|
[25] |
Endocyte. Folic Acid-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors[DB]. ClinicalTrials.gov Identifier: NCT01999738, 2018.
|
[26] |
Endocyte. An Exploratory Study of the Folic Acid-tubulysin conjugate EC1456 in ovarian cancer subjects undergoing surgery[DB]. ClinicalTrials.gov Identifier: NCT03011320, 2018.
|
[27] |
Ghosh A, Heston W D W. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer[J]. J Cell Biochem, 2004, 91(3): 528-539.
|
[28] |
Silver D A, Pellicer I, Fair W R, et al. Prostate-specific membrane antigen expression in normal and malignant human tissues[J]. Clin Cancer Res, 1997, 3(1): 81-85.
|
[29] |
Perner S, Hofer M D, Kim R, et al. Prostate-specific membrane antigen expression as a predictor of prostate cancer progression[J]. Hum Pathol, 2007, 38(5): 696-701.
|
[30] |
Afshar-Oromieh A, Babich J W, Kratochwil C, et al. The rise of PSMA ligands for diagnosis and therapy of prostate cancer[J]. J Nucl Med, 2016, 57(Suppl 3): 79S-89S.
|
[31] |
Virgolini I, Decristoforo C, Uprimny C, et al. Current status of theranostics in prostate cancer[J]. Eur J Nucl Med Mol Imaging, 2018, 45(3): 471-495.
|
[32] |
Hillier S M, Maresca K P, Lu G, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer[J]. J Nucl Med, 2013, 54(8): 1369-1376.
|
[33] |
Vallabhajosula S, Nikolopoulou A, Babich J W, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen: pharmacokinetics and biodistribution studies in healthy subjects and patients with metastatic prostate cancer[J]. J Nucl Med, 2014, 55(11): 1791-1798.
|
[34] |
Schmidkonz C, Hollweg C, Beck M, et al. 99mTc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer[J]. Prostate (Hoboken, NJ, U S), 2018, 78(1): 54-63.
|
[35] |
Santos-Cuevas C, Davanzo J, FerroFlores G, et al. 99mTc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients[J]. Nucl Med Biol, 2017, 52: 1-6.
|
[36] |
Reff M E, Carner K, Chambers K S, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20[J]. Blood, 1994, 83(2): 435-445.
|
[37] |
Li N, Wang X, Lin B, et al. Clinical evaluation of 99mTc-rituximab for sentinel lymph node mapping in breast cancer patients[J]. J Nucl Med, 2016, 57(8): 1214-1220.
|
[38] |
Gmeiner S T, Fettich J, Zver S, et al. 99mTc-labelled rituximab, a new non-Hodgkin’s lymphoma imaging agent: first clinical experience[J]. Nucl Med Commun, 2008, 29(12): 1059-1065.
|
[39] |
Malviya G, Anzola K L, Podesta E, et al. 99mTc-labeled rituximab for imaging B lymphocyte infiltration in inflammatory autoimmune disease patients[J]. Mol Imaging Biol, 2012, 14(5): 637-646.
|
[40] |
Plow E F, Haas T A, Zhang L, et al. Ligand binding to integrins[J]. J Biol Chem, 2000, 275(29): 21785-21788.
|
[41] |
Brooks P C, Clark Ra F, Cheresh D A. Requirement of vascular integrin αvβ3 for angiogenesis[J]. Science, 1994, 264(5 158): 569-571.
|
[42] |
Jia B, Liu Z, Zhu Z, et al. Blood clearance kinetics, biodistribution, and radiation dosimetry of a kit-formulated integrin αvβ3-selective radiotracer 99mTc-3PRGD 2 in non-human primates[J]. Mol Imaging Biol, 2011, 13(4): 730-736.
|
[43] |
Cheng G H, Gao S, Ji T F, et al. Pharmacokinetics and radiation dosimetry of Tc-99m 3PRGD2 in healthy individuals: A pilot study[J]. Nuclear Science And Techniques, 2012, 23(6): 349-354.
|
[44] |
Zhu Z H, Miao W B, Li Q W, et al. 99mTc-3PRGD2 for integrin receptor imaging of lung cancer: a multicenter study[J]. Journal of Nuclear Medicine, 2012, 53(5): 716-722.
|
[45] |
Jin X, Liang N, Wang M, et al. Integrin imaging with Tc-99m-3PRGD2 SPECT/CT shows high specificity in the diagnosis of lymph node metastasis from non-small cell lung cancer[J]. Radiology, 2016, 281(3): 958-966.
|
[46] |
Yu X, Wu Y, Liu H, et al. Small-animal SPECT/CT of the progression and recovery of rat liver fibrosis by using an integrin αvβ3-targeting radiotracer[J]. Radiology, 2016, 279(2): 502-512.
|
[47] |
Huang C, Zheng Q, Miao W B. Study of novel molecular probe Tc-99m-3PRGD(2) in the diagnosis of rheumatoid arthritis[J]. Nuclear Medicine Communications, 2015, 36(12): 1208-1214.
|
[48] |
Chen G, Ouyang Z, Wang F, et al. Evaluation of Tc-99m-3PRGD2 integrin receptor imaging in the differential diagnosis of breast lesions and comparison with mammography[J]. Cancer Investigation, 2017, 35(2): 108-115.
|
[49] |
Wu Y, Zhang G J, Wang X C, et al. Early detection of rheumatoid arthritis in rats and humans with Tc-99m-3PRGD2 scintigraphy: imaging synovial neoangiogenesis[J]. Oncotarget, 2017, 8(4): 5753-5760.
|
[50] |
Zhang Z Q, Zhao X M, Ding C M, et al. Tc-99m-3PRGD2 SPECT/CT imaging for monitoring early response of EGFR-TKIs therapy in patients with advanced-stage lung adenocarcinoma[J]. Cancer Biotherapy And Radiopharmaceuticals, 2016, 31(7): 238-245.
|
[51] |
Hua J, Dobrucki L W, Sadeghi M M, et al. Noninvasive imaging of angiogenesis with a 99mTc-labeled peptide targeted at αvβ3 integrin after murine hindlimb ischemia[J]. Circulation, 2005, 111(24): 3255-3260.
|
[52] |
Bach-Gansmo T, Danielsson R, Saracco A, et al. Integrin receptor imaging of breast cancer: a proof-of-concept study to evaluate 99mTc-NC100692[J]. J Nucl Med, 2006, 47(9): 1434-1439.
|
[53] |
Bach-Gansmo T, Bogsrud T V, Skretting A. Integrin scintimammography using a dedicated breast imaging, solid-state gamma-camera and 99mTc-labelled NC100692[J]. Clin Physiol Funct Imaging, 2008, 28(4): 235-239.
|
[54] |
Axelsson R, Bach-Gansmo T, Castell-Conesa J, et al. An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the alpha v beta 3-selective angiogenesis imaging agent 99mTc-NC100692[J]. Acta Radiol, 2010, 51(1): 40-46.
|
[55] |
Gerke V, Moss S E. Annexins: From structure to function[J]. Physiol Rev, 2002, 82(2): 331-371.
|
[56] |
Wang X, Feng H, Zhao S, et al. SPECT and PET radiopharmaceuticals for molecular imaging of apoptosis: from bench to clinic[J]. Oncotarget, 2017, 8(12): 20476-20495.
|
[57] |
Van De Wiele C, Vermeersch H, Loose D, et al. Radiolabeled annexin-V for monitoring treatment response in oncology[J]. Cancer Biother Radiopharm, 2004, 19(2): 189-194.
|
[58] |
Kemerink G J, Boersma H H, Thimister P W, et al. Biodistribution and dosimetry of99mTc-BTAP-annexin-V in humans[J]. Eur J Nucl Med, 2001, 28(9): 1373-1378.
|
[59] |
Kemerink G J, Liem I H, Hofstra L, et al. Patient dosimetry of intravenously administered Tc-99m-annexin V[J]. Journal of Nuclear Medicine, 2001, 42(2): 382-387.
|
[60] |
Kartachova M, Van Zandwijk N, Burgers S, et al. Prognostic significance of Tc-99m Hynic-rh-annexin V scintigraphy during platinum-based chemotherapy in advanced lung cancer[J]. Journal of Clinical Oncology, 2007, 25(18): 2534-2539.
|
[61] |
Rottey S, Loose D, Vakaet L, et al.99mTc-HYNIC Annexin-V imaging of tumors and its relationship to response to radiotherapy and/or chemotherapy[J]. Q J Nucl Med Mol Imaging, 2007, 51(2): 182-188.
|
[62] |
Rottey S, Van Den Bossche B, Slegers G, et al. Influence of chemotherapy on the biodistribution of Tc-99m hydrazinonicotinamide annexin V in cancer patients[J]. Quarterly Journal of Nuclear Medicine and Molecular Imaging, 2009, 53(2): 127-132.
|
[63] |
Kemerink G J, Liu X, Kieffer D, et al. Safety, biodistribution, and dosimetry of99mTc-HYNIC-annexin V, a novel human recombinant annexin V for human application[J]. J Nucl Med, 2003, 44(6): 947-952.
|
[64] |
Blankenberg F G, Katsikis P D, Tait J F, et al. In vivo detection and imaging of phosphatidylserine expression during programmed cell death[J]. Proc Natl Acad Sci USA, 1998, 95(11): 6349-6354.
|
[65] |
Stratton J R, Dewhurst T A, Kasina S, et al. Selective uptake of radiolabeled annexin V on acute porcine left atrial thrombi[J]. Circulation, 1995, 92(10): 3113-3121.
|
[66] |
Hilgenbrink A R, Low P S. Folate receptor-mediated drug targeting: from therapeutics to diagnostics[J]. J Pharm Sci, 2005, 94(10): 2135-2146.
|
[67] |
Leamon C P, Parker M A, Vlahov I R, et al. Synthesis and biological evaluation of EC20: a new folate-derived,99mTc-based radiopharmaceutical[J]. Bioconjugate Chem, 2002, 13(6): 1200-1210.
|
[68] |
Fisher R E, Siegel B A, Edell S L, et al. Exploratory study of99mTc-EC20 imaging for identifying patients with folate receptor-positive solid tumors[J]. J Nucl Med, 2008, 49(6): 899-906.
|
[69] |
Naumann R W, Coleman R L, Burger R A, et al. PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer[J]. J Clin Oncol, 2013, 31(35): 4400-4406.
|
[70] |
Herzog T J, Kutarska E, Bidzinsk M, et al. Adverse event profile by folate receptor status for vintafolide and pegylated liposomal doxorubicin in combination, versus pegylated liposomal doxorubicin alone, in platinum-resistant ovarian cancer: exploratory analysis of the phase Ⅱ PRECEDENT trial[J]. Int J Gynecol Cancer, 2016, 26(9): 1580-1585.
|
[71] |
Yamada Y, Nakatani H, Yanaihara H, et al. Phase I clinical trial of99mTc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults[J]. Ann Nucl Med, 2015, 29(9): 792-798.
|
[72] |
Morris R T, Joyrich R N, Naumann R W, et al. Phase II study of treatment of advanced ovarian cancer with folate-receptor-targeted therapeutic (vintafolide) and companion SPECT-based imaging agent (99mTc-etarfolatide)[J]. Ann Oncol, 2014, 25(4): 852-858.
|
[73] |
European Medicines Agency[EB/OL]. http:∥www.ema.europa.eu/ema(accessed 18 April 2018).
|
[74] |
Yang D J, Kim C G, Schechter N R, et al. Imaging with 99mTc ECDG targeted at the multifunctional glucose transport system: feasibility study with rodents[J]. Radiology, 2003, 226(2): 465-473.
|
[75] |
Yang D, Yukihiro M, Yu D-F, et al. Assessment of therapeutic tumor response using99mTc-ethylenedicysteine-glucosamine[J]. Cancer Biother Radiopharm, 2004, 19(4): 443-456.
|
[76] |
Angelides S, El-Mashaleh M, Anagnostou M, et al. The role of99mTc-labelled glucosamine (99mTc-ECDG) in the evaluation of rheumatic joint disease: a screening experience[J]. Nucl Med Commun, 2014, 35(6): 655-665.
|
[77] |
Ginat D T, Westiin C, Chin C T, et al. Pilot study of99mTc-labeled ethylene dicysteine deoxyglucose SPECT-CT imaging in treatment response evaluation in patients with locally advanced head and neck cancer[J]. Cureus, 2017, 9(4): e1152.
|
[78] |
张俊波,张旭冉,甘倩倩,等. 99mTc-标记含异腈的葡萄糖衍生物及制备方法和应用:中国,CN201710451094.8[P]. 2017-10-13.
|
[79] |
Hernandez-Valdes D, Alberto R, Jauregui-Haza U. Quantum chemistry calculations of technetium and rhenium compounds with application in radiopharmacy: review[J]. RSC Adv, 2016, 6(108): 107127-107140.
|
[80] |
Wang X Y, Wang Y, Liu XQ, et al. The structure, energy and stability of components formed in the preparation of fac-[99mTc(CO)3(H2O)3]+[J]. Phys Chem Chem Phys, 2003, 5(3): 456-460.
|
[81] |
Jia H M, Fang D C, Feng Y, et al. The interconversion mechanism between TcO3+ and TcO2+ core of 99mTc-labeled amine-oxime (AO) complexes[J]. Theor Chem Acc, 2008, 121(5-6): 271-278.
|
[82] |
Jia H, Ma X, Wang C, et al. Solvation effects on brain uptakes of isomers of 99mTc brain imaging agents[J]. Chin Sci Bull, 2002, 47(21): 1786-1791.
|
[83] |
Pascu S, Dilworth J. Recent developments in PET and SPECT imaging[J]. J Labelled Compd Radiopharm, 2014, 57(4): 191-194.
|
[84] |
Bailey D L, Willowson K P. An evidence-based review of quantitative SPECT imaging and potential clinical applications[J]. J Nucl Med, 2013, 54(1): 83-89.
|
[85] |
Mariani G, Bruselli L, Duatti A. Is PET always an advantage versus planar and SPECT imaging?[J]. Eur J Nucl Med Mol Imaging, 2008, 35(8): 1560-1565.
|
[86] |
Hutton B F, Erlandsson K, Thielemans K. Advances in clinical molecular imaging instrumentation[J]. Clinical and Translational Imaging, 2018, 6(1): 31-45.
|
[87] |
Adak S, Bhalla R, Raj K K V, et al. Radiotracers for SPECT imaging: current scenario and future prospects[J]. Radiochim Acta, 2012, 100(2): 95-107.
|
[88] |
Srivastava S C. Paving the way to personalized medicine: production of some theragnostic radionuclides at Brookhaven national laboratory[J]. Radiochim Acta, 2011, 99(10): 635-640.
|
[89] |
De Rosales R T M, Blower P. Chapter 16 Role of 99mTc in the Development of Rhenium Radiopharmaceuticals[C]∥International Atomic Energy Agency. Thechnetium-99m-Radiopharmaceuticals:Status-and-Trends.IAEA-Radioisotopes and Radiopharmaceuticals. Series No. 1. Vienna: IAEA, 2009: 317-346.
|
[90] |
Zhang X, Hou Y, Peng C, et al. Oligoethyleneoxy-modified 99mTc-labeled β-amyloid imaging probes with improved brain pharmacokinetics for single-photon emission computed tomography[J]. J Med Chem, 2018, 61(3): 1330-1339.
|
[91] |
Wang X, Li D, Deuther-Conrad W, et al. Novel cyclopentadienyl tricarbonyl 99mTc-complexes containing 1-piperonylpiperazine moiety: potential imaging probes for sigma-1 receptors[J]. J Med Chem, 2014, 57(16): 7113-7125.
|
[92] |
Alberto R. Chapter 17 Future Trends in the Development of Technetium Radiopharmaceuticals[C]∥ International Atomic Energy Agency. Thechnetium-99m Radiopharmaceuticals:Status and Trends. IAEA Radioisotopes and Radiopharmaceuticals. Series No.1. Vienna: IAEA, 2009: 347-358.
|
[93] |
Li D, Chen Y, Wang X, et al. 99mTc-Cyclopentadienyl tricarbonyl chelate-labeled compounds as selective sigma-2 receptor ligands for tumor imaging[J]. J Med Chem, 2016, 59(3): 934-946.
|
|
|
|