新型固体靶核素89Zr的制备、标记和临床前应用研究进展

doi:10.7538/tws.2018.youxian.041

摘要/Abstract

摘要：

利用正电子核素标记抗体进行PET免疫显像是筛选适合抗体靶向治疗的重要方法，正电子核素锆-89（⁸⁹Zr）由于其较长的半衰期使其成为PET免疫显像的理想核素，同时⁸⁹Zr核素还可用于制备纳米粒子、微球等，其在临床上的应用越来越广泛。本文对固体靶核素⁸⁹Zr的制备、标记以及临床前应用等进行调研，了解国内外⁸⁹Zr的制备方法和工艺，探索先进的标记方法，并讨论其在肿瘤临床诊疗的应用价值。

关键词: 回旋加速器, 固体靶, ⁸⁹Zr, PET免疫显像, 抗体

Abstract:

Recently, positron emission tomography/computed tomography (PET/CT) has expanded to become a routine diagnostic study of particular importance in oncology in treatment evaluation and management. In particle, immuno-PET which uses positron nuclide labeled antibodies, antibody fragments, and peptides for the in vivo molecular imaging is one of the most important methods for selecting effective targeted therapy patients. Due to its longer half-life meeting with the body clearance rate of antibodies, positron radionuclide zirconium-89(⁸⁹Zr) has become the ideal nuclide for immuno-PET. The current most common route to produce ⁸⁹Zr is via cyclotron through the ⁸⁹Y(p,n)⁸⁹Zr nuclear reaction using natural abundance yttrium-89(⁸⁹Y) foil. Meanwhile, higher activity recovery method for ⁸⁹Zr using the hydroxamate resin purification has become the standardized method in most paper reports. As DFO is currently the most promising chelator for ⁸⁹Zr, so it is important to select an adequate conjugation of DFO to an antibody. Over the last years, several ⁸⁹Zr labeled antibodies directed against different tumor types have been evaluated in preclinical studies. Furthermore, ⁸⁹Zr can also be used to prepare nanoparticles and microspheres. It has become more and more useful in the clinical application. However, in China, there is no company or institute can provide nuclide ⁸⁹Zr continually and steadily. So it is very necessary and important to carry out series of researches on the production, purification and conjugation strategies of ⁸⁹Zr. Accordingly, ⁸⁹Zr based immunoPET in the preclinical oncology studies will be developed and apply to clinical practice gradually. In this paper, the solid target production methods and isolation of ⁸⁹Zr are investigated. The antibodies labeling methods and the preclinical application value in cancer are discussed.

Key words: cyclotron, solid target, Zirconium-89, immuno-PET, antibody

王风;朱华;李立强;郭晓轶;刘特立;杨志. 新型固体靶核素⁸⁹Zr的制备、标记和临床前应用研究进展[J]. 同位素, 2020, 33(2): 117-123.

WANG Feng;ZHU Hua;LI Liqiang;GUO Xiaoyi;LIU Teli;YANG Zhi. Progress in the Production, Labeling of Novel Solid Target Zirconium-89 and its Preliminary Application in the Preclinical[J]. Journal of Isotopes, 2020, 33(2): 117-123.

参考文献

［1］Thomas B, David W T, Tony B. A combined PET/CT scanner for clinical oncology［J］. J Nucl Med, 2000, 41: 1369-1379.
［2］Adams H J A, Klerk J M H, Fijnheer R, et al. Prognostic superiority of the national comprehensive cancer network international prognostic index over pretreatment whole-body volumetric-metabolic FDG-PET/CT metrics in diffuse large B-cell lymphoma［J］. Eur J Haematol, 2015, 94: 532-539.
［3］Dave S R, Samuel T A, Pucar D,et al. FDG PET/CT in evaluation of unusual cutaneous manifestations of breast cancer［J］. Clin Nucl Med, 2015, 40: 63-67.
［4］Giovannini E, Lazzeri P, Milano A. et al. Clinical applications of choline PET/CT in brain tumors［J］. Current Pharmaceutical Design, 2015, 21(1): 121-127.
［5］Jauw Y W S, Hoekstra O S, Hendrikse N H, et al. Immuno-positron emission tomography with Zirconium-89-labeled monoclonal antibodies in oncology: what can we learn from initial clinical trials?［J］. Front Pharmacol, 2016, 7: 131.
［6］Lamberts T E, Menkevan C W, Ter Weele E J, et al. ImmunoPET with anti-mesothelin antibody in patients with pancreatic and ovarian cancer before anti-mesothelin antibody-drug conjugate treatment［J］. Clinical Cancer Research, 2015, 22(7): 1642-1652.
［7］Fischer G, Seibold U, Schirrmacher R, et al. ⁸⁹Zr, a radiometal nuclide with high potential fomolecular imaging with PET: chemistry, applications and remaining challenges［J］. Molecules, 2013, 18(6): 6469-6490.
［8］Fc V D W, Rijpkema M, Perk L, et al. Zirconium-89 labeled antibodies: a new tool for molecular imaging in cancer patients［J］. Biomed Research International, 2014(10-12): 203 601.
［9］Holland J P, Williamson M J, Lewis J S. Unconventional nuclides for radiopharmaceuticals［J］. Molecular imaging, 2010, 9(1): 1-20.
［10］Lubberink M, Herzog H. Quantitative imaging of I-124 and Y-86 with PET［J］. Eur J Nucl Med Mol I, 2011, 38: 10-18.
［11］Tang Y, Li S, Yang Y, et al. A simple and convenient method for production of ⁸⁹Zr with high purity［J］. Applied Radiation and Isotopes, 2016, 118: 326-330.
［12］Tang L. Radionuclide production and yields at Washington University School of Medicine［J］. Q J Nucl Med Mol Imaging, 2008, 52(2): 121-133.
［13］Dabkowski A M, Probst K, Marshall C. Cyclotron production for the radiometal Zirconium-89 with an IBA cyclone 18/9 and COSTIS solid target system (STS)［J］. Christopher Marshall, 2012, 1509(1): 108-113.
［14］Meijs W E, Herscheid J D M, Haisma H J, et al. Production of highly pure no-carrier added ⁸⁹Zr for the labelling of antibodies with a positron emitter［J］. Appl Radiat Isot, 1994, 45(12): 1143-1147.
［15］Wadas T J, Wong E H, Weisman G R, et al. Coordinating radiometals of copper, gallium, indium, yttrium, and zirconium for PET and SPECT imaging of disease［J］. Chem Rev, 2010, 110(5): 2858.
［16］Ciarmatori A, Cicoria G, Pancaldi D, et al. Some experimental studies on ⁸⁹Zr production［J］. International Journal for Chemical Aspects of Nuclear Science & Technology, 2011, 99(10): 1-4.
［17］Infantino A, Cicoria G, Pancaldi D, et al. Prediction of ⁸⁹Zr production using the Monte Carlo code FLUKA［J］. Applied Radiation and Isotopes, 2011, 69(8): 1134-1137.
［18］Zweit J, Downey S, Sharma H L. Production of no-carrier-added zirconium-89 for positron emission tomography［J］. International Journal of Radiation Applications & Instrumentation part Applied Radiation & Isotopes, 1991, 42(2): 199-201.
［19］Vosjan M J W D, Perk L R, Visser G W M, et al. Conjugation and radiolabeling of monoclonal antibodies with zirconium-89 for PET imaging using the bifunctional chelate p-isothiocyanatobenzyl-desferrioxamine［J］. Nat Protoc, 2010, 5: 739-743.
［20］Yin Z, Hao H, Cai W. PET tracers based on zirconium-89［J］. Curr Radiopharm,2011, 4(2): 131-139.
［21］Meijs W E, Haisma H J, Vander S R, et al. A facile method for the labeling of proteins with zirconium isotopes［J］. Nucl Med Biol, 1996, 23: 439-448.
［22］Verel I, Visser G W M, Boellaard R, et al. Zr-89 immuno-PET: comprehensive procedures for the production of Zr-89-labeled monoclonal antibodies［J］. J Nucl Med,2003, 44: 1271-1281.
［23］Perk L R, Vosjan M J W D, Visser G W M, et al. P-isothiocyanatobenzyl-desferrioxamine: a new bifunctional chelate for facile radiolabeling of monoclonal antibodies with zirconium-89 for immuno-PET imaging［J］. European Journal of Nuclear Medicine & Molecular Imaging, 2010, 37(2): 250-259.
［24］Chen L, Han X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future［J］. J Clin Invest, 2015, 125(9): 3384-3391.
［25］Perk L R, Visser O J, Stigter-van W M, et al. Preparation and evaluation of ⁸⁹Zr-Zevalin for monitoring of ⁹⁰Y-Zevalin biodistribution with positron emission tomography［J］. European Journal of Nuclear Medicine and Molecular Imaging, 2006, 33(11): 1337-1345.
［26］Yeh H H, Ogawa K, Balatoni J,et al. Molecular imaging of active mutant L858R EGF receptor (EGFR) kinase-expressing nonsmall cell lung carcinomas using PET/CT［J］. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(4): 1603-1608.
［27］Heuveling D A, Visser G W M, Baclayon M, et al. Zr-89-Nanocolloidal albuminbased PET/CT lymphoscintigraphy for sentinel node detection in head and neck cancer: preclinical results［J］. J Nucl Med,2011, 52: 1580-1584.
［28］Keliher E J, Yoo J, Nahrendorf M, et al. ⁸⁹Zr labeled dextran nanoparticles allow in vivo macrophage imaging［J］. Bioconjug Chem, 2015, 22(12): 2383-2389.
［29］Avila-Rodriguez M A, Selwyn R G, Hampel J A, et al. Positron-emitting resin microspheres as surrogates of Y-90 SIR-Spheres: a radiolabeling and stability study［J］. Nucl Med Biol, 2007, 34: 585-590.
［30］Ruggiero A, Villa C H, HollandJ, et al. Imaging and treating tumor vasculature with targeted radiolabeled carbon nanotubes［J］. Int J Nanomed, 2010, 5: 783-802.
［31］Abou D S, Thorek D L, Ramos N N,et al. ⁸⁹Zr-Labeled paramagnetic octreotide-liposomes for PETMR imaging of cancer［J］. Pharm Res, 2013, 30: 878-888.

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新型固体靶核素⁸⁹Zr的制备、标记和临床前应用研究进展

Progress in the Production, Labeling of Novel Solid Target Zirconium-89 and its Preliminary Application in the Preclinical

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