Stand der Technik in der Radiopharmazie

Zusammenfassung

Die wachsende Zahl potenzieller Radioisotope und die steigende Nachfrage nach Radiopharmazeutika (RP) für Bildgebung- und Therapiezwecke haben dazu geführt, dass ihre biomedizinische Anwendung im modernen Gesundheitswesen immer mehr an Bedeutung gewinnt. Die nuklearmedizinische Technologie wird heute als ein wesentliches Instrument für Diagnose, Palliation, Therapie und theranostische Anwendungen angesehen. Die damit verbundene Produktion unter Einhaltung der guten Herstellungspraxis (GMP) und Fragen der Strahlensicherheit müssen in Form von angemessenen Regulierungsmaßnahmen hervorgehoben werden, um ihren sicheren und wirksamen Einsatz zu gewährleisten. Die RP ziehen aufgrund ihrer pharmazeutischen und radioaktiven Bestandteile die Aufmerksamkeit sowohl der pharmazeutischen als auch der gesundheitstechnischer Aufsichtsbehörden auf sich. Diese Arbeit gibt einen kurzen Überblick über die RP und die jüngsten Studien zur diagnostischen, therapeutischen und theranostischen Anwendung. Die vorliegende Arbeit erörtert die Bedeutung von RP im aktuellen Gesundheitsbereich, ihre jüngsten Anwendungen und bemüht sich, die Bedeutung eines harmonisierten Regelwerkes hervorzuheben.

Abstract

The growing number of potential radioisotopes and the increasing demand for radiopharmaceuticals (RPs) for imaging and therapeutic purposes have led to their biomedical application becoming increasingly important in modern healthcare. Nuclear medicine technology is now considered an essential tool for diagnosis, palliation, therapy and theranostic applications. The associated production in compliance with Good Manufacturing Practices (GMP) and radiation safety issues need to be emphasized in the form of appropriate regulatory measures to ensure their safe and effective use. Radiopharmaceuticals attract the attention of both pharmaceutical and health regulatory authorities due to their pharmaceutical and radioactive components. This work provides a brief overview on radiopharmaceuticals and recent studies reporting their diagnostic, therapeutic and theranostic use. This paper discusses the importance of RPs in the current health field and their recent applications, and intends to highlight the importance of a harmonized regulatory framework.

Schlüsselwörter

Radioisotope - Herstellung von Radiopharmazeutika - Bildgebung - Therapie

Keywords

Radioisotopes - production of radiopharmaceuticals - imaging - therapy

Publication History

Article published online:
16 August 2022

• Referenzen

• 1 Hargreaves RJ. The role of molecular imaging in drug discovery and development. Clin Pharmacol Ther 2008; 83: 349-353
• 2 Phelps ME, Coleman RE. Nuclear medicine in the new millennium. J Nucl Med 2000; 41: 1-4
• 3 Price EW, Orvig C. Matching chelators to radiometals for radiopharmaceuticals. Chem Soc Rev 2014; 43: 260-290
• 4 Aerts J, Ballinger JR, Behe M. et al. Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective. J Labelled Comp Radiopharm 2014; 57: 615-620
• 5 Staiger C. ["Radiologic health" The history of radiopharmacy]. Pharm Unserer Zeit 2005; 34: 454-459
• 6 Rahmim A, Zaidi H. PET versus SPECT: strengths, limitations and challenges. Nucl Med Commun 2008; 29: 193-207
• 7 Hicks RJ, Hofman MS. Is there still a role for SPECT-CT in oncology in the PET-CT era?. Nat Rev Clin Oncol 2012; 9: 712-720
• 8 Pascu S, Dilworth J. Recent developments in PET and SPECT imaging. J Labelled Comp Radiopharm 2014; 57: 191-194
• 9 de Rosales RT. Potential clinical applications of bimodal PET-MRI or SPECT-MRI agents. J Labelled Comp Radiopharm 2014; 57: 298-303
• 10 Bhattacharyya S, Dixit M. Metallic radionuclides in the development of diagnostic and therapeutic radiopharmaceuticals. Dalton Trans 2011; 40: 6112-6128
• 11 Holland JP, Williamson MJ, Lewis JS. Unconventional nuclides for radiopharmaceuticals. Mol Imaging 2010; 9: 1-20
• 12 Bartholoma MD, Louie AS, Valliant JF. et al. Technetium and gallium derived radiopharmaceuticals: comparing and contrasting the chemistry of two important radiometals for the molecular imaging era. Chem Rev 2010; 110: 2903-2920
• 13 Calabretta R, Castello A, Giglioli C. et al. Prognostic value of divergent pattern detection by 99mTc-sestamibi gated SPECT in patients with anterior acute myocardial infarction. J Nucl Cardiol 2021;
• 14 Kikuchi A, Wada N, Kawakami T. et al. A myocardial extraction method using deep learning for 99mTc myocardial perfusion SPECT images: A basic study to reduce the effects of extra-myocardial activity. Comput Biol Med 2022; 141: 105164
• 15 Shipulin VV, Andreev SL, Pryakhin AS. et al. Low-dose dobutamine stress gated blood pool SPECT assessment of left ventricular contractile reserve in ischemic cardiomyopathy: a feasibility study. Eur J Nucl Med Mol Imaging 2022;
• 16 Best SRD, Haustrup N, Pavel DG. Brain SPECT as an Imaging Biomarker for Evaluating Effects of Novel Treatments in Psychiatry-A Case Series. Front Psychiatry 2021; 12: 713141
• 17 Rafidi H, Estevez A, Ferl GZ. et al. Imaging Reveals Importance of Shape and Flexibility for Glomerular Filtration of Biologics. Mol Cancer Ther 2021; 20: 2008-2015
• 18 An YS, Park DY, Min BH. et al. Comparison of bone single-photon emission computed tomography (SPECT)/CT and bone scintigraphy in assessing knee joints. BMC Med Imaging 2021; 21: 60
• 19 Cheng KT. (99m)Tc-Arcitumomab Molecular Imaging and Contrast Agent Database (MICAD) Bethesda (MD). 2004
• 20 Willkomm P, Bender H, Bangard M. et al. FDG PET and immunoscintigraphy with 99mTc-labeled antibody fragments for detection of the recurrence of colorectal carcinoma. J Nucl Med 2000; 41: 1657-1663
• 21 Robu S, Schottelius M, Eiber M. et al. Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer. J Nucl Med 2017; 58: 235-242
• 22 Hou G, Jiang Y, Li F. et al. Site-based performance of 131I-MIBG imaging and 99mTc-HYNIC-TOC scintigraphy in the detection of nonmetastatic extra-adrenal paraganglioma. Nucl Med Commun 2022; 43: 32-41
• 23 Anzola LK, Rivera JN, Dierckx RA. et al. Value of Somatostatin Receptor Scintigraphy with (99m)Tc-HYNIC-TOC in Patients with Primary Sjogren Syndrome. J Clin Med 2019; 8
• 24 D'Alessandria C, di Gialleonardo V, Chianelli M. et al. Synthesis and optimization of the labeling procedure of 99mTc-HYNIC-interleukin-2 for in vivo imaging of activated T lymphocytes. Mol Imaging Biol 2010; 12: 539-546
• 25 Roca Jungfer M, Abram U. [Tc(OH2)(CO)3(PPh3)2](+): A Synthon for Tc(I) Complexes and Its Reactions with Neutral Ligands. Inorg Chem 2021; 60: 16734-16753
• 26 Psimadas D, Fani M, Gourni E. et al. Synthesis and comparative assessment of a labeled RGD peptide bearing two different (9)(9)mTc-tricarbonyl chelators for potential use as targeted radiopharmaceutical. Bioorg Med Chem 2012; 20: 2549-2557
• 27 Verona M, Rubagotti S, Croci S. et al. Preliminary Study of a 1,5-Benzodiazepine-Derivative Labelled with Indium-111 for CCK-2 Receptor Targeting. Molecules 2021; 26
• 28 Bandari RP, Carmack TL, Malhotra A. et al. Development of Heterobivalent Theranostic Probes Having High Affinity/Selectivity for the GRPR/PSMA. J Med Chem 2021; 64: 2151-2166
• 29 Nabi HA, Erb DA, Cronin VR. Superiority of SPET to planar imaging in the detection of colorectal carcinomas with 111In monoclonal antibodies. Nucl Med Commun 1995; 16: 631-639
• 30 Schuster DM, Nieh PT, Jani AB. et al. Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography and (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial. J Urol 2014; 191: 1446-1453
• 31 Khaw BA. Antibodies for molecular imaging in the cardiovascular system. J Nucl Cardiol 2005; 12: 591-604
• 32 Favaretto C, Talip Z, Borgna F. et al. Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging. EJNMMI Radiopharm Chem 2021; 6: 37
• 33 Borgna F, Barritt P, Grundler PV. et al. Simultaneous Visualization of (161)Tb- and (177)Lu-Labeled Somatostatin Analogues Using Dual-Isotope SPECT Imaging. Pharmaceutics 2021; 13
• 34 Rosch F, Herzog H, Qaim SM. The Beginning and Development of the Theranostic Approach in Nuclear Medicine, as Exemplified by the Radionuclide Pair (86)Y and (90)Y. Pharmaceuticals (Basel) 2017; 10
• 35 Muller C, Zhernosekov K, Koster U. et al. A unique matched quadruplet of terbium radioisotopes for PET and SPECT and for alpha- and beta- radionuclide therapy: an in vivo proof-of-concept study with a new receptor-targeted folate derivative. J Nucl Med 2012; 53: 1951-1959
• 36 Umbricht CA, Koster U, Bernhardt P. et al. Alpha-PET for Prostate Cancer: Preclinical investigation using (149)Tb-PSMA-617. Sci Rep 2019; 9: 17800
• 37 Duran MT, Juget F, Nedjadi Y. et al. Determination of (161)Tb half-life by three measurement methods. Appl Radiat Isot 2020; 159: 109085
• 38 Baum RP, Singh A, Kulkarni HR. et al. First-in-Humans Application of (161)Tb: A Feasibility Study Using (161)Tb-DOTATOC. J Nucl Med 2021; 62: 1391-1397
• 39 Gracheva N, Muller C, Talip Z. et al. Production and characterization of no-carrier-added (161)Tb as an alternative to the clinically-applied (177)Lu for radionuclide therapy. EJNMMI Radiopharm Chem 2019; 4: 12
• 40 Chen K, Chen X. Design and development of molecular imaging probes. Curr Top Med Chem 2010; 10: 1227-1236
• 41 Conti M, Eriksson L. Physics of pure and non-pure positron emitters for PET: a review and a discussion. EJNMMI Phys 2016; 3: 8
• 42 Lapi SE, Welch MJ. A historical perspective on the specific activity of radiopharmaceuticals: what have we learned in the 35 years of the ISRC?. Nucl Med Biol 2012; 39: 601-608
• 43 Sergeev ME, Lazari M, Morgia F. et al. Performing radiosynthesis in microvolumes to maximize molar activity of tracers for positron emission tomography. Commun Chem 2018; 1
• 44 Synowiecki MA, Perk LR, Nijsen JFW. Production of novel diagnostic radionuclides in small medical cyclotrons. EJNMMI Radiopharm Chem 2018; 3: 3
• 45 Velikyan I. 68Ga-Based radiopharmaceuticals: production and application relationship. Molecules 2015; 20: 12913-12943
• 46 Kesch C, Kratochwil C, Mier W. et al. (68)Ga or (18)F for Prostate Cancer Imaging?. J Nucl Med 2017; 58: 687-688
• 47 Banerjee SR, Pomper MG. Clinical applications of Gallium-68. Appl Radiat Isot 2013; 76: 2-13
• 48 Ferreira CL, Lamsa E, Woods M. et al. Evaluation of bifunctional chelates for the development of gallium-based radiopharmaceuticals. Bioconjug Chem 2010; 21: 531-536
• 49 Satpati D. Recent Breakthrough in (68)Ga-Radiopharmaceuticals Cold Kits for Convenient PET Radiopharmacy. Bioconjug Chem 2021; 32: 430-447
• 50 Graham MM, Gu X, Ginader T. et al. (68)Ga-DOTATOC Imaging of Neuroendocrine Tumors: A Systematic Review and Metaanalysis. J Nucl Med 2017; 58: 1452-1458
• 51 Hennrich U, Benešová M. [(68)Ga]Ga-DOTA-TOC: The First FDA-Approved (68)Ga-Radiopharmaceutical for PET Imaging. Pharmaceuticals (Basel) 2020; 13
• 52 Poeppel TD, Binse I, Petersenn S. et al. 68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. J Nucl Med 2011; 52: 1864-1870
• 53 Hennrich U, Eder M. [(68)Ga]Ga-PSMA-11: The First FDA-Approved (68)Ga-Radiopharmaceutical for PET Imaging of Prostate Cancer. Pharmaceuticals (Basel) 2021; 14
• 54 Eder M, Schäfer M, Bauder-Wüst U. et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem 2012; 23: 688-697
• 55 Calderoni L, Farolfi A, Pianori D. et al. Evaluation of an Automated Module Synthesis and a Sterile Cold Kit-Based Preparation of (68)Ga-PSMA-11 in Patients with Prostate Cancer. J Nucl Med 2020; 61: 716-722
• 56 Lindner T, Loktev A, Altmann A. et al. Development of Quinoline-Based Theranostic Ligands for the Targeting of Fibroblast Activation Protein. J Nucl Med 2018; 59: 1415-1422
• 57 Hamson EJ, Keane FM, Tholen S. et al. Understanding fibroblast activation protein (FAP): substrates, activities, expression and targeting for cancer therapy. Proteomics Clin Appl 2014; 8: 454-463
• 58 Jiang GM, Xu W, Du J. et al. The application of the fibroblast activation protein α-targeted immunotherapy strategy. Oncotarget 2016; 7: 33472-33482
• 59 Giesel FL, Kratochwil C, Lindner T. et al. (68)Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers. J Nucl Med 2019; 60: 386-392
• 60 Hicks RJ, Roselt PJ, Kallur KG. et al. FAPI PET/CT: Will It End the Hegemony of (18)F-FDG in Oncology?. J Nucl Med 2021; 62: 296-302
• 61 Demmer O, Gourni E, Schumacher U. et al. PET imaging of CXCR4 receptors in cancer by a new optimized ligand. ChemMedChem 2011; 6: 1789-1791
• 62 Gourni E, Demmer O, Schottelius M. et al. PET of CXCR4 expression by a (68)Ga-labeled highly specific targeted contrast agent. J Nucl Med 2011; 52: 1803-1810
• 63 Juarez J, Bendall L, Bradstock K. Chemokines and their receptors as therapeutic targets: the role of the SDF-1/CXCR4 axis. Curr Pharm Des 2004; 10: 1245-1259
• 64 Pawig L, Klasen C, Weber C. et al. Diversity and Inter-Connections in the CXCR4 Chemokine Receptor/Ligand Family: Molecular Perspectives. Front Immunol 2015; 6: 429
• 65 Domanska UM, Kruizinga RC, Nagengast WB. et al. A review on CXCR4/CXCL12 axis in oncology: no place to hide. Eur J Cancer 2013; 49: 219-230
• 66 Feng Y, Broder CC, Kennedy PE. et al. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996; 272: 872-877
• 67 Nagafuchi Y, Shoda H, Sumitomo S. et al. Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity. Sci Rep 2016; 6: 29338
• 68 Wester HJ, Keller U, Schottelius M. et al. Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging. Theranostics 2015; 5: 618-630
• 69 Lapa C, Lückerath K, Kleinlein I. et al. (68)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma. Theranostics 2016; 6: 428-434
• 70 Lapa C, Lückerath K, Rudelius M. et al. [68Ga]Pentixafor-PET/CT for imaging of chemokine receptor 4 expression in small cell lung cancer--initial experience. Oncotarget 2016; 7: 9288-9295
• 71 Thackeray JT, Derlin T, Haghikia A. et al. Molecular Imaging of the Chemokine Receptor CXCR4 After Acute Myocardial Infarction. JACC Cardiovasc Imaging 2015; 8: 1417-1426
• 72 Sanchez-Crespo A. Comparison of Gallium-68 and Fluorine-18 imaging characteristics in positron emission tomography. Appl Radiat Isot 2013; 76: 55-62
• 73 Cai L, Lu S, Pike VW. Chemistry with [18F]Fluoride Ion. European Journal of Organic Chemistry 2008; 2008: 2853-2873
• 74 Jacobson O, Kiesewetter DO, Chen X. Fluorine-18 radiochemistry, labeling strategies and synthetic routes. Bioconjug Chem 2015; 26: 1-18
• 75 Long JZ, Jacobson MS, Hung JC. Comparison of FASTlab 18F-FDG production using phosphate and citrate buffer cassettes. J Nucl Med Technol 2013; 41: 32-34
• 76 McBride WJ, Sharkey RM, Karacay H. et al. A novel method of 18F radiolabeling for PET. J Nucl Med 2009; 50: 991-998
• 77 McBride WJ, Sharkey RM, Goldenberg DM. Radiofluorination using aluminum-fluoride (Al18F). EJNMMI Res 2013; 3: 36
• 78 Laverman P, McBride WJ, Sharkey RM. et al. A novel facile method of labeling octreotide with (18)F-fluorine. J Nucl Med 2010; 51: 454-461
• 79 Laverman P, D'Souza CA, Eek A. et al. Optimized labeling of NOTA-conjugated octreotide with F-18. Tumour Biol 2012; 33: 427-434
• 80 Tshibangu T, Cawthorne C, Serdons K. et al. Automated GMP compliant production of [(18)F]AlF-NOTA-octreotide. EJNMMI Radiopharm Chem 2020; 5: 4
• 81 Pauwels E, Cleeren F, Tshibangu T. et al. [(18)F]AlF-NOTA-octreotide PET imaging: biodistribution, dosimetry and first comparison with [(68)Ga]Ga-DOTATATE in neuroendocrine tumour patients. Eur J Nucl Med Mol Imaging 2020; 47: 3033-3046
• 82 Cleeren F, Lecina J, Ahamed M. et al. Al(18)F-Labeling Of Heat-Sensitive Biomolecules for Positron Emission Tomography Imaging. Theranostics 2017; 7: 2924-2939
• 83 Russelli L, Martinelli J, De Rose F. et al. Room Temperature Al(18) F Labeling of 2-Aminomethylpiperidine-Based Chelators for PET Imaging. ChemMedChem 2020; 15: 284-292
• 84 Entzian W, Aronow S, Soloway AH. et al. A PRELIMINARY EVALUATION OF F-18-LABELED TETRAFLUOROBORATE AS A SCANNING AGENT FOR INTRACRANIAL TUMORS. J Nucl Med 1964; 5: 542-550
• 85 Ting R, Adam MJ, Ruth TJ. et al. Arylfluoroborates and alkylfluorosilicates as potential PET imaging agents: high-yielding aqueous biomolecular 18F-labeling. J Am Chem Soc 2005; 127: 13094-13095
• 86 Liu Z, Lin KS, Bénard F. et al. One-step (18)F labeling of biomolecules using organotrifluoroborates. Nat Protoc 2015; 10: 1423-1432
• 87 Li Z, Chansaenpak K, Liu S. et al. Harvesting 18F-fluoride ions in water via direct 18F–19F isotopic exchange: radiofluorination of zwitterionic aryltrifluoroborates and in vivo stability studies. MedChemComm 2012; 3: 1305-1308
• 88 Pourghiasian M, Liu Z, Pan J. et al. (18)F-AmBF3-MJ9: a novel radiofluorinated bombesin derivative for prostate cancer imaging. Bioorg Med Chem 2015; 23: 1500-1506
• 89 Liu Z, Pourghiasian M, Bénard F. et al. Preclinical evaluation of a high-affinity 18F-trifluoroborate octreotate derivative for somatostatin receptor imaging. J Nucl Med 2014; 55: 1499-1505
• 90 Lau J, Pan J, Rousseau E. et al. Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [(18)F]AmBF(3)-TATE. EJNMMI Res 2020; 10: 25
• 91 Gens TA, Wethongton JA, Brosi AR. The Exchange of F18between Metallic Fluorides and Silicon Tetrafluoride. The Journal of Physical Chemistry 1958; 62: 1593-1593
• 92 Rosenthal MS, Bosch AL, Nickles RJ. et al. Synthesis and some characteristics of no-carrier added [18F]fluorotrimethylsilane. The International Journal of Applied Radiation and Isotopes 1985; 36: 318-319
• 93 Schirrmacher R, Bradtmöller G, Schirrmacher E. et al. 18F-labeling of peptides by means of an organosilicon-based fluoride acceptor. Angew Chem Int Ed Engl 2006; 45: 6047-6050
• 94 Höhne A, Yu L, Mu L. et al. Organofluorosilanes as model compounds for 18F-labeled silicon-based PET tracers and their hydrolytic stability: experimental data and theoretical calculations (PET = positron emission tomography). Chemistry 2009; 15: 3736-3743
• 95 Wängler C, Waser B, Alke A. et al. One-step ¹⁸F-labeling of carbohydrate-conjugated octreotate-derivatives containing a silicon-fluoride-acceptor (SiFA): in vitro and in vivo evaluation as tumor imaging agents for positron emission tomography (PET). Bioconjug Chem 2010; 21: 2289-2296
• 96 Niedermoser S, Chin J, Wängler C. et al. In Vivo Evaluation of ¹⁸F-SiFAlin-Modified TATE: A Potential Challenge for ⁶⁸Ga-DOTATATE, the Clinical Gold Standard for Somatostatin Receptor Imaging with PET. J Nucl Med 2015; 56: 1100-1105
• 97 Lindner S, Michler C, Leidner S. et al. Synthesis and in vitro and in vivo evaluation of SiFA-tagged bombesin and RGD peptides as tumor imaging probes for positron emission tomography. Bioconjug Chem 2014; 25: 738-749
• 98 Litau S, Niedermoser S, Vogler N. et al. Next Generation of SiFAlin-Based TATE Derivatives for PET Imaging of SSTR-Positive Tumors: Influence of Molecular Design on In Vitro SSTR Binding and In Vivo Pharmacokinetics. Bioconjug Chem 2015; 26: 2350-2359
• 99 Wurzer A, Di Carlo D, Schmidt A. et al. Radiohybrid Ligands: A Novel Tracer Concept Exemplified by (18)F- or (68)Ga-Labeled rhPSMA Inhibitors. J Nucl Med 2020; 61: 735-742
• 100 Feuerecker B, Chantadisai M, Allmann A. et al. Pre-therapeutic comparative dosimetry of (177)Lu-rhPSMA-7.3 and (177)Lu-PSMAI&T in patients with metastatic castration resistant prostate cancer (mCRPC). J Nucl Med 2021;
• 101 Wurzer A, Di Carlo D, Herz M. et al. Automated synthesis of [(18)F]Ga-rhPSMA-7/ -7.3: results, quality control and experience from more than 200 routine productions. EJNMMI Radiopharm Chem 2021; 6: 4
• 102 Oh SW, Wurzer A, Teoh EJ. et al. Quantitative and Qualitative Analyses of Biodistribution and PET Image Quality of a Novel Radiohybrid PSMA, (18)F-rhPSMA-7, in Patients with Prostate Cancer. J Nucl Med 2020; 61: 702-709
• 103 Eiber M, Kroenke M, Wurzer A. et al. (18)F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy. J Nucl Med 2020; 61: 696-701
• 104 Kroenke M, Wurzer A, Schwamborn K. et al. Histologically Confirmed Diagnostic Efficacy of (18)F-rhPSMA-7 PET for N-Staging of Patients with Primary High-Risk Prostate Cancer. J Nucl Med 2020; 61: 710-715
• 105 Dai L, Zhang J, Wong CT. et al. Design of Functional Chiral Cyclen-Based Radiometal Chelators for Theranostics. Inorg Chem 2021; 60: 7082-7088
• 106 Majkowska-Pilip A, Bilewicz A. Macrocyclic complexes of scandium radionuclides as precursors for diagnostic and therapeutic radiopharmaceuticals. J Inorg Biochem 2011; 105: 313-320
• 107 Polosak M, Piotrowska A, Krajewski S. et al. Stability of (47)Sc-complexes with acyclic polyamino-polycarboxylate ligands. J Radioanal Nucl Chem 2013; 295: 1867-1872
• 108 Chakravarty R, Goel S, Valdovinos HF. et al. Matching the decay half-life with the biological half-life: ImmunoPET imaging with (44)Sc-labeled cetuximab Fab fragment. Bioconjug Chem 2014; 25: 2197-2204
• 109 Vaughn BA, Ahn SH, Aluicio-Sarduy E. et al. Chelation with a twist: a bifunctional chelator to enable room temperature radiolabeling and targeted PET imaging with scandium-44. Chem Sci 2020; 11: 333-342
• 110 Nagy G, Szikra D, Trencsenyi G. et al. AAZTA: An Ideal Chelating Agent for the Development of (44) Sc PET Imaging Agents. Angew Chem Int Ed Engl 2017; 56: 2118-2122
• 111 Eppard E, de la Fuente A, Benesova M. et al. Clinical Translation and First In-Human Use of [(44)Sc]Sc-PSMA-617 for PET Imaging of Metastasized Castrate-Resistant Prostate Cancer. Theranostics 2017; 7: 4359-4369
• 112 Ghiani S, Hawala I, Szikra D. et al. Synthesis, radiolabeling, and pre-clinical evaluation of [(44)Sc]Sc-AAZTA conjugate PSMA inhibitor, a new tracer for high-efficiency imaging of prostate cancer. Eur J Nucl Med Mol Imaging 2021; 48: 2351-2362
• 113 Jauw YW, Menke-van der Houven van Oordt CW, Hoekstra OS. et al. Immuno-Positron Emission Tomography with Zirconium-89-Labeled Monoclonal Antibodies in Oncology: What Can We Learn from Initial Clinical Trials?. Front Pharmacol 2016; 7: 131
• 114 Vosjan MJ, Perk LR, Visser GW. et al. Conjugation and radiolabeling of monoclonal antibodies with zirconium-89 for PET imaging using the bifunctional chelate p-isothiocyanatobenzyl-desferrioxamine. Nat Protoc 2010; 5: 739-743
• 115 Poot AJ, Adamzek KWA, Windhorst AD. et al. Fully Automated (89)Zr Labeling and Purification of Antibodies. J Nucl Med 2019; 60: 691-695
• 116 Bhatt NB, Pandya DN, Rideout-Danner S. et al. A comprehensively revised strategy that improves the specific activity and long-term stability of clinically relevant (89)Zr-immuno-PET agents. Dalton Trans 2018; 47: 13214-13221
• 117 Yoon JK, Park BN, Ryu EK. et al. Current Perspectives on (89)Zr-PET Imaging. Int J Mol Sci 2020; 21
• 118 Niemeijer AN, Leung D, Huisman MC. et al. Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer. Nat Commun 2018; 9: 4664
• 119 Lewis J, Laforest R, Buettner T. et al. Copper-64-diacetyl-bis(N4-methylthiosemicarbazone): An agent for radiotherapy. Proc Natl Acad Sci U S A 2001; 98: 1206-1211
• 120 Castillo AX, Perez-Malo M, Isaac-Olive K. et al. Production of large quantities of 90Y by ion-exchange chromatography using an organic resin and a chelating agent. Nucl Med Biol 2010; 37: 935-942
• 121 Mohsin H, Jia F, Sivaguru G. et al. Radiolanthanide-labeled monoclonal antibody CC49 for radioimmunotherapy of cancer: biological comparison of DOTA conjugates and 149Pm, 166Ho, and 177Lu. Bioconjug Chem 2006; 17: 485-492
• 122 Dash A, Pillai MR, Knapp FF. et al. Production of (177)Lu for Targeted Radionuclide Therapy: Available Options. Nucl Med Mol Imaging 2015; 49: 185-107
• 123 Pillai MR, Chakraborty S, Das T. et al. Production logistics of 177Lu for radionuclide therapy. Appl Radiat Isot 2003; 59: 109-118
• 124 Gabriel M, Oberauer A, Dobrozemsky G. et al. 68Ga-DOTA-Tyr3-octreotide PET for assessing response to somatostatin-receptor-mediated radionuclide therapy. J Nucl Med 2009; 50: 1427-1434
• 125 Lattuada L, Barge A, Cravotto G. et al. The synthesis and application of polyamino polycarboxylic bifunctional chelating agents. Chem Soc Rev 2011; 40: 3019-3049
• 126 Banerjee S, Pillai MR, Knapp FF. Lutetium-177 therapeutic radiopharmaceuticals: linking chemistry, radiochemistry, and practical applications. Chem Rev 2015; 115: 2934-2974
• 127 Liu S, Edwards DS. Bifunctional chelators for therapeutic lanthanide radiopharmaceuticals. Bioconjug Chem 2001; 12: 7-34
• 128 Marcus R. Use of 90Y-ibritumomab tiuxetan in non-Hodgkin's lymphoma. Semin Oncol 2005; 32: S36-43
• 129 Boswell CA, Brechbiel MW. Development of radioimmunotherapeutic and diagnostic antibodies: an inside-out view. Nucl Med Biol 2007; 34: 757-778
• 130 Kwekkeboom DJ, Teunissen JJ, Bakker WH. et al. Radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 2005; 23: 2754-2762
• 131 Poty S, Francesconi LC, McDevitt MR. et al. alpha-Emitters for Radiotherapy: From Basic Radiochemistry to Clinical Studies-Part 1. J Nucl Med 2018; 59: 878-884
• 132 Boll RA, Malkemus D, Mirzadeh S. Production of actinium-225 for alpha particle mediated radioimmunotherapy. Appl Radiat Isot 2005; 62: 667-679
• 133 McDevitt MR, Ma D, Lai LT. et al. Tumor therapy with targeted atomic nanogenerators. Science 2001; 294: 1537-1540
• 134 Thiele NA, Brown V, Kelly JM. et al. An Eighteen-Membered Macrocyclic Ligand for Actinium-225 Targeted Alpha Therapy. Angew Chem Int Ed Engl 2017; 56: 14712-14717
• 135 Muller C, van der Meulen NP, Benesova M. et al. Therapeutic Radiometals Beyond (177)Lu and (90)Y: Production and Application of Promising alpha-Particle, beta(-)-Particle, and Auger Electron Emitters. J Nucl Med 2017; 58: 91S-96S
• 136 Beyer GJ, Miederer M, Vranjes-Duric S. et al. Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab. Eur J Nucl Med Mol Imaging 2004; 31: 547-554
• 137 Muller C, Reber J, Haller S. et al. Folate receptor targeted alpha-therapy using terbium-149. Pharmaceuticals (Basel) 2014; 7: 353-365
• 138 Muller C, Vermeulen C, Koster U. et al. Alpha-PET with terbium-149: evidence and perspectives for radiotheragnostics. EJNMMI Radiopharm Chem 2017; 1: 5
• 139 Gillings N, Hjelstuen O, Ballinger J. et al. Guideline on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. EJNMMI Radiopharm Chem 2021; 6: 8
• 140 Lever SZ. Evolution of radiopharmaceuticals for diagnosis and therapy. J Cell Biochem Suppl 2002; 39: 60-64
• 141 Saha GB. Production of Radionuclides. In Physics and Radiobiology of Nuclear Medicine. New York, NY, USA: Springer; 2006: 44-55
• 142 Synowiecki MA, Perk LFW, Nijsen JA. Production of novel diagnostic radionuclides in small medical cyclotrons. EJNMMI Radiopharm Chem. 2018; 3: 3