68Ga-Based Radiopharmaceuticals: Production and Application Relationship

Springer Science and Business Media LLC - Tập 20 Số 7 - Trang 12913-12943
Irina Velikyan1,2
1PET Center, Center for Medical Imaging, Uppsala University Hospital, Uppsala SE-751 85, Sweden 
2Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala SE-751 85, Sweden

Tóm tắt

The contribution of 68Ga to the promotion and expansion of clinical research and routine positron emission tomography (PET) for earlier better diagnostics and individualized medicine is considerable. The potential applications of 68Ga-comprising imaging agents include targeted, pre-targeted and non-targeted imaging. This review discusses the key aspects of the production of 68Ga and 68Ga-based radiopharmaceuticals in the light of the impact of regulatory requirements and endpoint pre-clinical and clinical applications.

Từ khóa


Tài liệu tham khảo

Velikyan, 2014, Prospective of 68Ga-radiopharmaceutical development, Theranostics, 4, 47, 10.7150/thno.7447

Velikyan, 2012, Molecular imaging and radiotherapy: Theranostics for personalized patient management, Theranostics, 2, 424, 10.7150/thno.4428

Chen, X., and Wong, S. (2014). Cancer Theranostics, Elsevier.

Velikyan, 2011, Positron emitting [68Ga]Ga-based imaging agents: Chemistry and diversity, Med. Chem., 7, 338, 10.2174/157340611796799195

Velikyan, 2013, The diversity of 68Ga-based imaging agents, Recent Results Cancer Res., 194, 101, 10.1007/978-3-642-27994-2_7

Velikyan, I. (2015). Continued rapid growth in Ga applications: Update 2013 to june 2014. J. Label. Compd. Radiopharm., 99–121.

Blom, 2009, 68Ga-labeling of biotin analogues and their characterization, Bioconjugate Chem., 20, 1146, 10.1021/bc800538s

Eriksson, 2012, Preclinical evaluation of a 68Ga-labeled biotin analogue for applications in islet transplantation, Nucl. Med. Biol., 39, 415, 10.1016/j.nucmedbio.2011.09.009

Selvaraju, 2013, In vivo imaging of the glucagonlike peptide 1 receptor in the pancreas with 68Ga-labeled do3a-exendin-4, J. Nucl. Med., 54, 1458, 10.2967/jnumed.112.114066

Velikyan, 2010, In vivo binding of [68Ga]-dotatoc to somatostatin receptors in neuroendocrine tumours—Impact of peptide mass, Nucl. Med. Biol., 37, 265, 10.1016/j.nucmedbio.2009.11.008

Sorensen, 2014, Measuring her2-expression in metastatic breast cancer using 68Ga-aby025 pet/ct, Eur. J. Nucl. Med. Mol. Imaging, 41, S226

Velikyan, 2014, Gmp compliant preparation of a 68Gallium-labeled affibody analogue for breast cancer patient examination: First-in-man, Eur. J. Nucl. Med. Mol. Imaging, 41, S228

Bé, M.M., and Schönfeld, E. Table de Radionucléide. Available online: http://www.nucleide.org/DDEP_WG/DDEPdata.htm.

McCutchan, 2012, Nuclear Data Sheets for A = 68, Nucl. Data Sheets, 113, 1735, 10.1016/j.nds.2012.06.002

Romero, 2014, Measurement of the half-life of 68Ga, Appl. Radiat. Isot., 87, 122, 10.1016/j.apradiso.2013.11.082

(2011). European Pharmacopeia 7.7 (01/2013:2482 Gallium (68Ga) Edotreotide injection). Eur Pharm., 23, 310–313.

European Pharmacopeia (2013). Gallium (68 Ga) chloride solution for radiolabelling. Eur Pharm., 2464, 1060–1061. European Directorate for the Quality of Medicines.

Velikyan, 2004, Microwave-supported preparation of 68Ga-bioconjugates with high specific radioactivity, Bioconjugate Chem., 15, 554, 10.1021/bc030078f

Rosch, 2013, Past, present and future of 68Ge/68Ga generators, Appl. Radiat. Isot., 76, 24, 10.1016/j.apradiso.2012.10.012

Nakayama, 2002, Separation of Ga-68 from Ge-68 using a macroporous organic polymer containing n-methylglucamine groups, Anal. Chim. Acta, 453, 135, 10.1016/S0003-2670(01)01484-2

Le, 2013, 68Ga generator integrated system: Elution-purification-concentration integration, Recent Results Cancer Res., 194, 43, 10.1007/978-3-642-27994-2_4

Chattopadhyay, 2013, Preparation and evaluation of sno2-based 68Ge/68Ga generator made from 68Ge produced through natzn(α,xn) reaction, Appl. Radiat. Isot., 79, 42, 10.1016/j.apradiso.2013.04.019

Chakravarty, 2013, Long-term evaluation of “barc 68Ge/68Ga generator” based on the nanoceria-polyacrylonitrile composite sorbent, Cancer Biother. Radiopharm., 28, 631

Gleason, 1960, A positron cow, Int. J. Appl. Radiat. Isot., 8, 90, 10.1016/0020-708X(60)90052-1

Yano, Y. (1971). Preparation and Control of 68Ga Radiopharmaceuticals, International Atomic Energy Agency.

Chan, 2011, Reduction of 68Ge activity containing liquid waste from 68Ga pet chemistry in nuclear medicine and radiopharmacy by solidification, J. Radioanal. Nucl. Chem., 288, 303, 10.1007/s10967-010-0915-8

Petrik, 2012, Microbial challenge tests on nonradioactive tio2-based 68Ge/68Ga generator columns, Nucl. Med. Commun., 33, 819, 10.1097/MNM.0b013e3283543323

Breeman, 2005, Radiolabelling dota-peptides with 68Ga, Eur. J. Nucl. Med. Mol. Imaging, 32, 478, 10.1007/s00259-004-1702-y

Schultz, 2013, A new automated nacl based robust method for routine production of gallium-68 labeled peptides, Appl. Radiat. Isot., 76, 46, 10.1016/j.apradiso.2012.08.011

Velikyan, 2012, Robust labeling and comparative preclinical characterization of dota-toc and dota-tate, Nucl. Med. Biol., 39, 628, 10.1016/j.nucmedbio.2011.12.010

Mueller, 2012, Simplified nacl based 68Ga concentration and labeling procedure for rapid synthesis of 68Ga radiopharmaceuticals in high radiochemical purity, Bioconjugate Chem., 23, 1712, 10.1021/bc300103t

Loktionova, 2011, Improved column-based radiochemical processing of the generator produced 68Ga, Appl. Radiat. Isot., 69, 942, 10.1016/j.apradiso.2011.02.035

Gebhardt, 2010, Computer controlled Ga-68 milking and concentration system, Appl. Radiat. Isot., 68, 1057, 10.1016/j.apradiso.2010.01.024

Zhernosekov, 2007, Processing of generator-produced 68Ga for medical application, J. Nucl. Med., 48, 1741, 10.2967/jnumed.107.040378

Meyer, 2004, 68Ga-labelled dota-derivatised peptide ligands, Eur. J. Nucl. Med. Mol. Imaging, 31, 1097, 10.1007/s00259-004-1486-0

Eppard, 2014, Ethanol-based post-processing of generator-derived 68Ga toward kit-type preparation of 68Ga-radiopharmaceuticals, J. Nucl. Med., 55, 1023, 10.2967/jnumed.113.133041

Petrik, 2010, Impurity in 68Ga-peptide preparation using processed generator eluate, J. Nucl. Med., 51, 495, 10.2967/jnumed.109.070953

Bauwens, 2010, Optimal buffer choice of the radiosynthesis of Ga-68-dotatoc for clinical application, Nucl. Med. Commun., 31, 753, 10.1097/MNM.0b013e32833acb99

Velikyan, 2008, The importance of high specific radioactivity in the performance of 68Ga-labeled peptide, Nucl. Med. Biol., 35, 529, 10.1016/j.nucmedbio.2008.03.002

Velikyan, 2008, Convenient preparation of 68Ga-based pet-radiopharmaceuticals at room temperature, Bioconjugate Chem., 19, 569, 10.1021/bc700341x

Notni, 2011, Trap, a powerful and versatile framework for Gallium-68 radiopharmaceuticals, Chem. Eur. J., 17, 14718, 10.1002/chem.201103503

Oehlke, 2013, Influence of metal ions on the 68Ga-labeling of dotatate, Appl. Radiat. Isot., 82, 232, 10.1016/j.apradiso.2013.08.010

Simecek, 2013, How is 68Ga labeling of macrocyclic chelators influenced by metal ion contaminants in 68Ge/68Ga generator eluates?, ChemMedChem, 8, 95, 10.1002/cmdc.201200471

Chakravarty, 2013, Detailed evaluation on the effect of metal ion impurities on complexation of generator eluted 68Ga with different bifunctional chelators, Nucl. Med. Biol., 40, 197, 10.1016/j.nucmedbio.2012.11.001

Zhai, 2015, Fusarinine c, a novel siderophore-based bifunctional chelator for radiolabeling with Gallium-68, J. Label. Compd. Radiopharm., 58, 209, 10.1002/jlcr.3286

Borges, 2011, Ventilation distribution studies comparing technegas and gallgas using 68GaCl3 as the label, J. Nucl. Med., 52, 206, 10.2967/jnumed.110.083881

Velikyan, 2014, Quantitative and qualitative intrapatient comparison of 68Ga-dotatoc and 68Ga-dotatate: Net uptake rate for accurate quantification, J. Nucl. Med., 55, 204, 10.2967/jnumed.113.126177

Velikyan, 2013, Comparative biodistribution and radiation dosimetry of 68Ga- dotatoc and 68Ga-dotatate in patients with neuroendocrine tumors, J. Nucl. Med., 54, 1755, 10.2967/jnumed.113.120600

Reubi, 2000, Affinity profiles for human somatostatin receptor subtypes sst1-sst5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use, Eur. J. Nucl. Med. Mol. Imaging, 27, 273, 10.1007/s002590050034

Eriksson, 2014, Detection of metastatic insulinoma by positron emission tomography with [68Ga]exendin-4-a case report, J. Clin. Endocrinol. Metab., 99, 1519, 10.1210/jc.2013-3541

Aime, 1996, Crystal structure and solution dynamics of the lutetium(iii) chelate of dota, Inorg. Chim. Acta, 246, 423, 10.1016/0020-1693(96)05130-4

Heppeler, 1999, Radiometal-labelled macrocyclic chelator-derivatised somatostatin analogue with superb tumour-targeting properties and potential for receptor-mediated internal radiotherapy, Chem. Eur. J., 5, 1974, 10.1002/(SICI)1521-3765(19990702)5:7<1974::AID-CHEM1974>3.0.CO;2-X

Velikyan, 2015, Dosimetry of [177Lu]-DO3A-VS-Cys40-Exendin-4—impact on the feasibility of insulinoma internal radiotherapy, Am. J. Nucl. Med. Mol. Imaging, 5, 109

Selvaraju, 2015, Dosimetry of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 in rodents, pigs, non-human primates and human-repeated scanning in human is possible, Am. J. Nucl. Med. Mol. Imaging, 5, 259

Decristoforo, 2014, Radiopharmaceuticals are special, but is this recognized? The possible impact of the new clinical trials regulation on the preparation of radiopharmaceuticals, Eur. J. Nucl. Med. Mol. Imaging, 41, 2005, 10.1007/s00259-014-2838-z

Decristoforo, 2009, Towards a harmonized radiopharmaceutical regulatory framework in europe?, Q. J. Nucl. Med. Mol. Imaging, 53, 394

Verbruggen, 2008, Guideline to regulations for radiopharmaceuticals in early phase clinical trials in the EU, Eur. J. Nucl. Med. Mol. Imaging, 35, 2144, 10.1007/s00259-008-0853-7

Norenberg, 2010, Operation of a radiopharmacy for a clinical trial, Semin. Nucl. Med., 40, 347, 10.1053/j.semnuclmed.2010.06.002

Lange, 2015, Untangling the web of european regulations for the preparation of unlicensed radiopharmaceuticals: A concise overview and practical guidance for a risk-based approach, Nucl. Med. Commun., 36, 414, 10.1097/MNM.0000000000000276

Aerts, 2014, Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: A european perspective, J. Label. Compd. Radiopharm., 57, 615, 10.1002/jlcr.3227

Elsinga, 2010, Guidance on current good radiopharmacy practice (cgrpp) for the small-scale preparation of radiopharmaceuticals, Eur. J. Nucl. Med. Mol. Imaging, 37, 1049, 10.1007/s00259-010-1407-3

Virgolini, 2010, Procedure guidelines for pet/ct tumour imaging with 68Ga-dota-conjugated peptides: 68Ga-dota-toc, 68Ga-dota-noc, 68Ga-dota-tate, Eur. J. Nucl. Med. Mol. Imaging, 37, 2004, 10.1007/s00259-010-1512-3

Janson, 2014, Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms, Acta Oncol., 53, 1284, 10.3109/0284186X.2014.941999

Marchetti, 2007, The impact of fda and emea guidelines on drug development in relation to phase 0 trials, Br. J. Cancer, 97, 577, 10.1038/sj.bjc.6603925

Mills, 2008, The exploratory ind, J. Nucl. Med., 49, 45N

Todde, 2014, Eanm guideline for the preparation of an investigational medicinal product dossier (impd), Eur. J. Nucl. Med. Mol. Imaging, 41, 2175, 10.1007/s00259-014-2866-8

Lappin, 2006, Use of microdosing to predict pharmacokinetics at the therapeutic dose: Experience with 5 drugs, Clin. Pharmacol. Ther., 80, 203, 10.1016/j.clpt.2006.05.008

Garner, 2006, The phase 0 microdosing concept, Br. J. Clin. Pharmacol., 61, 367, 10.1111/j.1365-2125.2006.02575.x

Bergstrom, 2003, Positron emission tomography microdosing: A new concept with application in tracer and early clinical drug development, Eur. J. Clin. Pharmacol., 59, 357, 10.1007/s00228-003-0643-x

(2006). Guidance for Industry, Investigators, and Reviewers, U.S. Department of Health and Human Services. Exploratory ind Studies.

Decristoforo, 2012, Feasibility and availability of 68Ga-labelled peptides, Eur. J. Nucl. Med. Mol. Imaging, 39, S31, 10.1007/s00259-011-1988-5

Velikyan, 2013, Organ biodistribution of germanium-68 in rat in the presence and absence of [68Ga]ga-dota-toc for the extrapolation to the human organ and whole-body radiation dosimetry, Am. J. Nucl. Med. Mol. Imaging, 3, 154

International Atomic Energy Agency Development of Ga-68 Based Pet-Radiopharmaceuticals for Management of Cancer and Other Chronic Diseases. Available online: http://cra.iaea.org/cra/explore-crps/all-active-by-programme.html.

Directive 2001/83/ec of the European Parliament and of the Council of 6 November 2001 on the Community Code Relating to Medicinal Products for Human Use. (Updated 2012).

Decristoforo, 2012, Gallium-68—A new opportunity for pet available from a long shelflife generator—automation and applications, Curr. Radiopharm., 5, 212, 10.2174/1874471011205030212

Boschi, 2013, Automation synthesis modules review, Appl. Radiat. Isot., 76, 38, 10.1016/j.apradiso.2012.09.010

Boschi, 2013, Overview and perspectives on automation strategies in 68Ga radiopharmaceutical preparations, Recent Results Cancer Res., 194, 17, 10.1007/978-3-642-27994-2_2