Login Register Cart 0
Generic placeholder image

Current Radiopharmaceuticals

Editor-in-Chief

ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

“One Method to Label Them All”: A Single Fully Automated Protocol for GMP-Compliant 68Ga Radiolabeling of PSMA-11, Transposable to PSMA-I&T and PSMA-617

Author(s): Juliette Fouillet, Charlotte Donzé, Emmanuel Deshayes, Lore Santoro, Léa Rubira and Cyril Fersing*

Volume 17, Issue 3, 2024

Published on: 28 February, 2024

Page: [285 - 301] Pages: 17

DOI: 10.2174/0118744710293461240219111852

open_access

Abstract

Background: Prostate-specific membrane antigen (PSMA) is an ideal target for molecular imaging and targeted radionuclide therapy in prostate cancer. Consequently, various PSMA ligands were developed. Some of these molecules are functionalized with a chelator that can host radiometals, such as 68Ga for PET imaging. The 68Ga radiolabeling step benefits from process automation, making it more robust and reducing radiation exposure.

Objective: To design a single automated radiolabeling protocol for the GMP-compliant preparation of [68Ga]Ga-PSMA-11, transposable to the production of [68Ga]Ga-PSMA-617 and [68Ga]Ga-PSMA-I&T.

Methods: A GAIA® synthesis module and a GALLIAD® generator were used. Radio-TLC and radio-HPLC methods were validated for radiochemical purity (RCP) determination. Three [68Ga]Ga-PSMA-11 validation batches were produced and thoroughly tested for appearance and pH, radionuclide identity and purity, RCP, stability, residual solvent and sterility. Minimal modifications were made to the reagents and disposables for optimal application to other PSMA ligands.

Results: [68Ga]Ga-PSMA-11 for clinical application was produced in 27 min. The 3 validation batches met the quality criteria expected by the European Pharmacopoeia to allow routine production. For optimal transposition to PSMA-617, the solid phase extraction cartridge was changed to improve purification of the radiolabeled product. For application to PSMA-I&T, the buffer solution initially used was replaced by HEPES 2.7 M to achieve good radiochemical yields. Residual HEPES content was checked in the final product and was below the Ph. Eur. threshold.

Conclusion: A single automated radiolabeling method on the GAIA® module was developed and implemented for 68Ga radiolabeling of 3 PSMA ligands, with slight adjustments for each molecule.

Keywords: PET imaging, prostate cancer, PSMA-11, PSMA-617, PSMA-I&T, 68Ga, automated synthesis, radiopharmacy.

« Previous Next »
Graphical Abstract

[1]
Horoszewicz, J.S.; Kawinski, E.; Murphy, G.P. Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res., 1987, 7(5B), 927-935.
[PMID: 2449118]
[2]
Carter, R.E.; Feldman, A.R.; Coyle, J.T. Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. Proc. Natl. Acad. Sci., 1996, 93(2), 749-753.
[http://dx.doi.org/10.1073/pnas.93.2.749] [PMID: 8570628]
[3]
Pinto, J.T.; Suffoletto, B.P.; Berzin, T.M.; Qiao, C.H.; Lin, S.; Tong, W.P.; May, F.; Mukherjee, B.; Heston, W.D. Prostate-specific membrane antigen: A novel folate hydrolase in human prostatic carcinoma cells. Clin. Cancer Res., 1996, 2(9), 1445-1451.
[PMID: 9816319]
[4]
Schülke, N.; Varlamova, O.A.; Donovan, G.P.; Ma, D.; Gardner, J.P.; Morrissey, D.M.; Arrigale, R.R.; Zhan, C.; Chodera, A.J.; Surowitz, K.G.; Maddon, P.J.; Heston, W.D.W.; Olson, W.C. The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy. Proc. Natl. Acad. Sci., 2003, 100(22), 12590-12595.
[http://dx.doi.org/10.1073/pnas.1735443100] [PMID: 14583590]
[5]
Israeli, R.S.; Powell, C.T.; Fair, W.R.; Heston, W.D. Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer Res., 1993, 53(2), 227-230.
[PMID: 8417812]
[6]
Leek, J.; Lench, N.; Maraj, B.; Bailey, A.; Carr, I.M.; Andersen, S.; Cross, J.; Whelan, P.; MacLennan, K.A.; Meredith, D.M.; Markham, A.F. Prostate-specific membrane antigen: Evidence for the existence of a second related human gene. Br. J. Cancer, 1995, 72(3), 583-588.
[http://dx.doi.org/10.1038/bjc.1995.377] [PMID: 7669565]
[7]
Davis, M.I.; Bennett, M.J.; Thomas, L.M.; Bjorkman, P.J. Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase. Proc. Natl. Acad. Sci., 2005, 102(17), 5981-5986.
[http://dx.doi.org/10.1073/pnas.0502101102] [PMID: 15837926]
[8]
Figueiredo, J.C.; Grau, M.V.; Haile, R.W.; Sandler, R.S.; Summers, R.W.; Bresalier, R.S.; Burke, C.A.; McKeown-Eyssen, G.E.; Baron, J.A. Folic acid and risk of prostate cancer: Results from a randomized clinical trial. J. Natl. Cancer Inst., 2009, 101(6), 432-435.
[http://dx.doi.org/10.1093/jnci/djp019] [PMID: 19276452]
[9]
Yao, V.; Berkman, C.E.; Choi, J.K.; O’Keefe, D.S.; Bacich, D.J. Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid. Prostate, 2010, 70(3), 305-316.
[http://dx.doi.org/10.1002/pros.21065] [PMID: 19830782]
[10]
Rycyna, K.J.; Bacich, D.J.; O’Keefe, D.S. Opposing roles of folate in prostate cancer. Urology, 2013, 82(6), 1197-1203.
[http://dx.doi.org/10.1016/j.urology.2013.07.012] [PMID: 23992971]
[11]
Carver, B.S.; Chapinski, C.; Wongvipat, J.; Hieronymus, H.; Chen, Y.; Chandarlapaty, S.; Arora, V.K.; Le, C.; Koutcher, J.; Scher, H.; Scardino, P.T.; Rosen, N.; Sawyers, C.L. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell, 2011, 19(5), 575-586.
[http://dx.doi.org/10.1016/j.ccr.2011.04.008] [PMID: 21575859]
[12]
Kaittanis, C.; Andreou, C.; Hieronymus, H.; Mao, N.; Foss, C.A.; Eiber, M.; Weirich, G.; Panchal, P.; Gopalan, A.; Zurita, J.; Achilefu, S.; Chiosis, G.; Ponomarev, V.; Schwaiger, M.; Carver, B.S.; Pomper, M.G.; Grimm, J. Prostate-specific membrane antigen cleavage of vitamin B9 stimulates oncogenic signaling through metabotropic glutamate receptors. J. Exp. Med., 2018, 215(1), 159-175.
[http://dx.doi.org/10.1084/jem.20171052] [PMID: 29141866]
[13]
Israeli, R.S.; Powell, C.T.; Corr, J.G.; Fair, W.R.; Heston, W.D. Expression of the prostate-specific membrane antigen. Cancer Res., 1994, 54(7), 1807-1811.
[PMID: 7511053]
[14]
Kinoshita, Y.; Kuratsukuri, K.; Landas, S.; Imaida, K.; Rovito, P.M., Jr; Wang, C.Y.; Haas, G.P. Expression of prostate-specific membrane antigen in normal and malignant human tissues. World J. Surg., 2006, 30(4), 628-636.
[http://dx.doi.org/10.1007/s00268-005-0544-5] [PMID: 16555021]
[15]
Uhlén, M.; Fagerberg, L.; Hallström, B.M.; Lindskog, C.; Oksvold, P.; Mardinoglu, A.; Sivertsson, Å.; Kampf, C.; Sjöstedt, E.; Asplund, A.; Olsson, I.; Edlund, K.; Lundberg, E.; Navani, S.; Szigyarto, C.A.K.; Odeberg, J.; Djureinovic, D.; Takanen, J.O.; Hober, S.; Alm, T.; Edqvist, P.H.; Berling, H.; Tegel, H.; Mulder, J.; Rockberg, J.; Nilsson, P.; Schwenk, J.M.; Hamsten, M.; von Feilitzen, K.; Forsberg, M.; Persson, L.; Johansson, F.; Zwahlen, M.; von Heijne, G.; Nielsen, J.; Pontén, F. Tissue-based map of the human proteome. Science, 2015, 347(6220), 1260419.
[http://dx.doi.org/10.1126/science.1260419] [PMID: 25613900]
[16]
Werner, R.A.; Sheikhbahaei, S.; Jones, K.M.; Javadi, M.S.; Solnes, L.B.; Ross, A.E.; Allaf, M.E.; Pienta, K.J.; Lapa, C.; Buck, A.K.; Higuchi, T.; Pomper, M.G.; Gorin, M.A.; Rowe, S.P. Patterns of uptake of prostate-specific membrane antigen (PSMA)-targeted 18F-DCFPyL in peripheral ganglia. Ann. Nucl. Med., 2017, 31(9), 696-702.
[http://dx.doi.org/10.1007/s12149-017-1201-4] [PMID: 28831739]
[17]
Debnath, S.; Zhou, N.; McLaughlin, M.; Rice, S.; Pillai, A.K.; Hao, G.; Sun, X. PSMA-Targeting imaging and theranostic agents—current status and future perspective. Int. J. Mol. Sci., 2022, 23(3), 1158.
[http://dx.doi.org/10.3390/ijms23031158] [PMID: 35163083]
[18]
Kozikowski, A.P.; Nan, F.; Conti, P.; Zhang, J.; Ramadan, E.; Bzdega, T.; Wroblewska, B.; Neale, J.H.; Pshenichkin, S.; Wroblewski, J.T. Design of remarkably simple, yet potent urea-based inhibitors of glutamate carboxypeptidase II (NAALADase). J. Med. Chem., 2001, 44(3), 298-301.
[http://dx.doi.org/10.1021/jm000406m] [PMID: 11462970]
[19]
Yang, X.; Mease, R.C.; Pullambhatla, M.; Lisok, A.; Chen, Y.; Foss, C.A.; Wang, Y.; Shallal, H.; Edelman, H.; Hoye, A.T.; Attardo, G.; Nimmagadda, S.; Pomper, M.G. [ 18 F]Fluorobenzoyllysinepentanedioic acid carbamates: New scaffolds for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA). J. Med. Chem., 2016, 59(1), 206-218.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01268] [PMID: 26629713]
[20]
Banerjee, S.R.; Foss, C.A.; Castanares, M.; Mease, R.C.; Byun, Y.; Fox, J.J.; Hilton, J.; Lupold, S.E.; Kozikowski, A.P.; Pomper, M.G. Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the prostate-specific membrane antigen (PSMA). J. Med. Chem., 2008, 51(15), 4504-4517.
[http://dx.doi.org/10.1021/jm800111u] [PMID: 18637669]
[21]
Eder, M.; Schäfer, M.; Bauder-Wüst, U.; Hull, W.E.; Wängler, C.; Mier, W.; Haberkorn, U.; Eisenhut, M. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug. Chem., 2012, 23(4), 688-697.
[http://dx.doi.org/10.1021/bc200279b] [PMID: 22369515]
[22]
Benešová, M.; Bauder-Wüst, U.; Schäfer, M.; Klika, K.D.; Mier, W.; Haberkorn, U.; Kopka, K.; Eder, M. Linker modification strategies to control the prostate-specific membrane antigen (PSMA)-targeting and pharmacokinetic properties of DOTA-Conjugated PSMA Inhibitors. J. Med. Chem., 2016, 59(5), 1761-1775.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01210] [PMID: 26878194]
[23]
Ray Banerjee, S.; Chen, Z.; Pullambhatla, M.; Lisok, A.; Chen, J.; Mease, R.C.; Pomper, M.G. Preclinical comparative study of 68 Ga-Labeled DOTA, NOTA, and HBED-CC chelated radiotracers for targeting PSMA. Bioconjug. Chem., 2016, 27(6), 1447-1455.
[http://dx.doi.org/10.1021/acs.bioconjchem.5b00679] [PMID: 27076393]
[24]
Eder, M.; Neels, O.; Müller, M.; Bauder-Wüst, U.; Remde, Y.; Schäfer, M.; Hennrich, U.; Eisenhut, M.; Afshar-Oromieh, A.; Haberkorn, U.; Kopka, K. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: A new PET tracer for imaging of prostate cancer. Pharmaceuticals, 2014, 7(7), 779-796.
[http://dx.doi.org/10.3390/ph7070779] [PMID: 24983957]
[25]
Benešová, M.; Schäfer, M.; Bauder-Wüst, U.; Afshar-Oromieh, A.; Kratochwil, C.; Mier, W.; Haberkorn, U.; Kopka, K.; Eder, M. Preclinical evaluation of a tailor-made DOTA-Conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J. Nucl. Med., 2015, 56(6), 914-920.
[http://dx.doi.org/10.2967/jnumed.114.147413] [PMID: 25883127]
[26]
Afshar-Oromieh, A.; Hetzheim, H.; Kratochwil, C.; Benesova, M.; Eder, M.; Neels, O.C.; Eisenhut, M.; Kübler, W.; Holland-Letz, T.; Giesel, F.L.; Mier, W.; Kopka, K.; Haberkorn, U. The theranostic PSMA Ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: Biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J. Nucl. Med., 2015, 56(11), 1697-1705.
[http://dx.doi.org/10.2967/jnumed.115.161299] [PMID: 26294298]
[27]
Weineisen, M.; Simecek, J.; Schottelius, M.; Schwaiger, M.; Wester, H.J. Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer. EJNMMI Res., 2014, 4(1), 63.
[http://dx.doi.org/10.1186/s13550-014-0063-1] [PMID: 26116124]
[28]
Weineisen, M.; Schottelius, M.; Simecek, J.; Baum, R.P.; Yildiz, A.; Beykan, S.; Kulkarni, H.R.; Lassmann, M.; Klette, I.; Eiber, M.; Schwaiger, M.; Wester, H.J. 68 Ga- and 177 Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies. J. Nucl. Med., 2015, 56(8), 1169-1176.
[http://dx.doi.org/10.2967/jnumed.115.158550] [PMID: 26089548]
[29]
Chen, Y.; Pullambhatla, M.; Foss, C.A.; Byun, Y.; Nimmagadda, S.; Senthamizhchelvan, S.; Sgouros, G.; Mease, R.C.; Pomper, M.G. 2-(3-1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer. Clin. Cancer Res., 2011, 17(24), 7645-7653.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-1357] [PMID: 22042970]
[30]
Meisenheimer, M.; Saenko, Y.; Eppard, E. Gallium-68: Radiolabeling of radiopharmaceuticals for pet imaging - a lot to consider. In: Medical Isotopes; Ali Raza Naqvi, S.; Babar Imrani, M., Eds.; IntechOpen, 2021.
[http://dx.doi.org/10.5772/intechopen.90615]
[31]
Taliaferro, C.H.; Martell, A.E. New Multidentate Ligands. XXVI: N,N′-Bis(2-Hydroxybenzyl)Ethylenediamine-N,N′--Bis(Methylenephosphonic Acid Monomethyl Ester), and N,N′--Bis(2-Hydroxybenzyl)Ethylenediamine-N,N′--Bis(Methylenephosphonic Acid Monoethyl Ester): New chelating ligands for trivalent metal ions. J. Coord. Chem., 1984, 13(3), 249-264.
[http://dx.doi.org/10.1080/00958978408073875]
[32]
Eder, M.; Wängler, B.; Knackmuss, S.; LeGall, F.; Little, M.; Haberkorn, U.; Mier, W.; Eisenhut, M. Tetrafluorophenolate of HBED-CC: A versatile conjugation agent for 68Ga-labeled small recombinant antibodies. Eur. J. Nucl. Med. Mol. Imaging, 2008, 35(10), 1878-1886.
[http://dx.doi.org/10.1007/s00259-008-0816-z] [PMID: 18509635]
[33]
Eder, M.; Krivoshein, A.V.; Backer, M.; Backer, J.M.; Haberkorn, U.; Eisenhut, M. ScVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA conjugates: Comparison of easy-to-label recombinant proteins for [68Ga]PET imaging of VEGF receptors in angiogenic vasculature. Nucl. Med. Biol., 2010, 37(4), 405-412.
[http://dx.doi.org/10.1016/j.nucmedbio.2010.02.001] [PMID: 20447550]
[34]
Ling, S.W.; de Blois, E.; Hooijman, E.; van der Veldt, A.; Brabander, T. Advances in 177Lu-PSMA and 225Ac-PSMA radionuclide therapy for metastatic castration-resistant prostate cancer. Pharmaceutics, 2022, 14(10), 2166.
[http://dx.doi.org/10.3390/pharmaceutics14102166] [PMID: 36297601]
[35]
Liu, C.; Liu, T.; Zhang, N.; Liu, Y.; Li, N.; Du, P.; Yang, Y.; Liu, M.; Gong, K.; Yang, X.; Zhu, H.; Yan, K.; Yang, Z. 68Ga-PSMA-617 PET/CT: A promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients. Eur. J. Nucl. Med. Mol. Imaging, 2018, 45(11), 1852-1861.
[http://dx.doi.org/10.1007/s00259-018-4037-9] [PMID: 29717333]
[36]
Wang, J.; Zang, J.; Wang, H.; Liu, Q.; Li, F.; Lin, Y.; Huo, L.; Jacobson, O.; Niu, G.; Fan, X.; Zhu, Z.; Chen, X. Pretherapeutic 68Ga-PSMA-617 PET May indicate the dosimetry of 177lu-psma-617 and 177lu-eb-psma-617 in main organs and tumor lesions. Clin. Nucl. Med., 2019, 44(6), 431-438.
[http://dx.doi.org/10.1097/RLU.0000000000002575] [PMID: 30985422]
[37]
Li, Y.; Han, D.; Wu, P.; Ren, J.; Ma, S.; Zhang, J.; Song, W.; Lin, X.; Jiao, D.; Shi, S.; Yang, F.; Wu, J.; Meng, P.; Wen, W.; Kang, F.; Wang, J.; Qin, W. Comparison of 68Ga-PSMA-617 PET/CT with mpMRI for the detection of PCa in patients with a PSA level of 4–20 ng/ml before the initial biopsy. Sci. Rep., 2020, 10(1), 10963.
[http://dx.doi.org/10.1038/s41598-020-67385-9] [PMID: 32620790]
[38]
Liu, D.; Cheng, G.; Ma, X.; Wang, S.; Zhao, X.; Zhang, W.; Yang, W.; Wang, J. PET/CT using 68 Ga‐PSMA‐617 versus18F fluorodeoxyglucose to differentiate low- and high-grade gliomas. J. Neuroimaging, 2021, 31(4), 733-742.
[http://dx.doi.org/10.1111/jon.12856] [PMID: 34021667]
[39]
Wang, G.; Zhou, M.; Zang, J.; Jiang, Y.; Chen, X.; Zhu, Z.; Chen, X. A pilot study of 68 Ga-PSMA-617 PET/CT imaging and 177Lu-EB-PSMA-617 radioligand therapy in patients with adenoid cystic carcinoma. EJNMMI Res., 2022, 12(1), 52.
[http://dx.doi.org/10.1186/s13550-022-00922-x] [PMID: 35984529]
[40]
Wang, G.; Hong, H.; Zang, J.; Liu, Q.; Jiang, Y.; Fan, X.; Zhu, Z.; Zhu, L.; Kung, H.F. Head-to-head comparison of [68 Ga]Ga-P16-093 and [68 Ga]Ga-PSMA-617 in dynamic PET/CT evaluation of the same group of recurrent prostate cancer patients. Eur. J. Nucl. Med. Mol. Imaging, 2022, 49(3), 1052-1062.
[http://dx.doi.org/10.1007/s00259-021-05539-1] [PMID: 34557930]
[41]
Lu, Q.; Long, Y.; Fan, K.; Shen, Z.; Gai, Y.; Liu, Q.; Jiang, D.; Cai, W.; Wan, C.; Lan, X. PET imaging of hepatocellular carcinoma by targeting tumor-associated endothelium using [68Ga]Ga-PSMA-617. Eur. J. Nucl. Med. Mol. Imaging, 2022, 49(12), 4000-4013.
[http://dx.doi.org/10.1007/s00259-022-05884-9] [PMID: 35763056]
[42]
Schollhammer, R.; Robert, G.; Asselineau, J.; Yacoub, M.; Vimont, D.; Balamoutoff, N.; Bladou, F.; Bénard, A.; Hindié, E.; Gallerande, H.C.; Morgat, C. Comparison of 68 Ga-PSMA-617 PET/CT and 68 Ga-RM2 PET/CT in patients with localized prostate cancer who are candidates for radical prostatectomy: A prospective, single-arm, single-center, phase II study. J. Nucl. Med., 2023, 64(3), 379-385.
[http://dx.doi.org/10.2967/jnumed.122.263889] [PMID: 36215569]
[43]
Gao, X.; Tang, Y.; Chen, M.; Li, J.; Yin, H.; Gan, Y.; Zu, X.; Cai, Y.; Hu, S. A prospective comparative study of [68Ga]Ga-RM26 and [68Ga]Ga-PSMA-617 PET/CT imaging in suspicious prostate cancer. Eur. J. Nucl. Med. Mol. Imaging, 2023, 50(7), 2177-2187.
[http://dx.doi.org/10.1007/s00259-023-06142-2] [PMID: 36811661]
[44]
Derlin, T.; Weiberg, D.; von Klot, C.; Wester, H.J.; Henkenberens, C.; Ross, T.L.; Christiansen, H.; Merseburger, A.S.; Bengel, F.M. 68Ga-PSMA I&T PET/CT for assessment of prostate cancer: Evaluation of image quality after forced diuresis and delayed imaging. Eur. Radiol., 2016, 26(12), 4345-4353.
[http://dx.doi.org/10.1007/s00330-016-4308-4] [PMID: 27011373]
[45]
Berliner, C.; Tienken, M.; Frenzel, T.; Kobayashi, Y.; Helberg, A.; Kirchner, U.; Klutmann, S.; Beyersdorff, D.; Budäus, L.; Wester, H.J.; Mester, J.; Bannas, P. Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [68Ga]PSMA I&T and comparison with published data of [68Ga]PSMA HBED-CC. Eur. J. Nucl. Med. Mol. Imaging, 2017, 44(4), 670-677.
[http://dx.doi.org/10.1007/s00259-016-3572-5] [PMID: 27896369]
[46]
Schmuck, S.; Mamach, M.; Wilke, F.; von Klot, C.A.; Henkenberens, C.; Thackeray, J.T.; Sohns, J.M.; Geworski, L.; Ross, T.L.; Wester, H.J.; Christiansen, H.; Bengel, F.M.; Derlin, T. Multiple time-point 68Ga-PSMA I&T PET/CT for characterization of primary prostate cancer. Clin. Nucl. Med., 2017, 42(6), e286-e293.
[http://dx.doi.org/10.1097/RLU.0000000000001589] [PMID: 28221194]
[47]
Schmuck, S.; Nordlohne, S.; von Klot, C.A.; Henkenberens, C.; Sohns, J.M.; Christiansen, H.; Wester, H.J.; Ross, T.L.; Bengel, F.M.; Derlin, T. Comparison of standard and delayed imaging to improve the detection rate of [68Ga]PSMA I&T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer. Eur. J. Nucl. Med. Mol. Imaging, 2017, 44(6), 960-968.
[http://dx.doi.org/10.1007/s00259-017-3669-5] [PMID: 28280856]
[48]
Meyrick, D.P.; Asokendaran, M.; Skelly, L.A.; Lenzo, N.P.; Henderson, A. The role of 68Ga-PSMA-I&T PET/CT in the pretreatment staging of primary prostate cancer. Nucl. Med. Commun., 2017, 38(11), 956-963.
[http://dx.doi.org/10.1097/MNM.0000000000000738] [PMID: 28922335]
[49]
Komek, H.; Can, C.; Yilmaz, U.; Altindag, S. Prognostic value of 68 Ga PSMA I&T PET/CT SUV parameters on survival outcome in advanced prostat cancer. Ann. Nucl. Med., 2018, 32(8), 542-552.
[http://dx.doi.org/10.1007/s12149-018-1277-5] [PMID: 30006752]
[50]
Yilmaz, U.; Komek, H.; Can, C.; Altindag, S. The role of (68Ga)PSMA I&T in biochemical recurrence after radical prostatectomy: Detection rate and the correlation between the level of PSA, Gleason score, and the SUVmax. Ann. Nucl. Med., 2019, 33(8), 545-553.
[http://dx.doi.org/10.1007/s12149-019-01360-x] [PMID: 31069696]
[51]
Cytawa, W.; Seitz, A.K.; Kircher, S.; Fukushima, K.; Tran-Gia, J.; Schirbel, A.; Bandurski, T.; Lass, P.; Krebs, M.; Połom, W.; Matuszewski, M.; Wester, H.J.; Buck, A.K.; Kübler, H.; Lapa, C. 68Ga-PSMA I&T PET/CT for primary staging of prostate cancer. Eur. J. Nucl. Med. Mol. Imaging, 2020, 47(1), 168-177.
[http://dx.doi.org/10.1007/s00259-019-04524-z] [PMID: 31529265]
[52]
Koehler, D.; Sauer, M.; Karimzadeh, A.; Apostolova, I.; Klutmann, S.; Adam, G.; Knipper, S.; Maurer, T.; Berliner, C. Evaluation of [68 Ga]Ga-PSMA-I&T PET/CT with additional late scans of the pelvis in prostate-specific antigen recurrence using the PROMISE criteria. EJNMMI Res., 2022, 12(1), 66.
[http://dx.doi.org/10.1186/s13550-022-00938-3] [PMID: 36210356]
[53]
Decristoforo, C. Gallium-68 - a new opportunity for PET available from a long shelf-life generator - automation and applications. Curr. Radiopharm., 2012, 5(3), 212-220.
[http://dx.doi.org/10.2174/1874471011205030212] [PMID: 22642389]
[54]
Szydlo, M.; Pogoda, D.; Kowalski, T.; Pociegiel, M.; Jadwinski, M.; Amico, A.d. Synthesis and quality control of 68Ga-PSMA PET/CT tracer used in Prostate cancer imaging and comparison with 18F-fluorocholine as a reference point. J. Pharm. Sci. Emerg. Drugs, 2018, 6, 1.
[55]
Assadi, M.; Dadgar, H. Quality control and GMP synthesis of 68Ga-prostate-specific membrane antigen-11 for detection of low- and high-grade prostate cancer. World J. Nucl. Med., 2019, 19(2), 93-98.
[PMID: 32939194]
[56]
Kleynhans, J.; Rubow, S.; le Roux, J.; Marjanovic-Painter, B.; Zeevaart, J.R.; Ebenhan, T. Production of [ 68 Ga]Ga-PSMA: Comparing a manual kit-based method with a module-based automated synthesis approach. J. Labelled Comp. Radiopharm., 2020, 63(13), 553-563.
[http://dx.doi.org/10.1002/jlcr.3879] [PMID: 32865290]
[57]
Garcia-Arguello, S.F.; Lopez-Lorenzo, B.; Ruiz-Cruces, R. Automated production of [ 68 Ga]Ga-DOTANOC and [ 68 Ga]Ga‐PSMA‐11 using a TRACERlab FX FN synthesis module. J. Labelled Comp. Radiopharm., 2019, 62(3), 146-153.
[http://dx.doi.org/10.1002/jlcr.3706] [PMID: 30672007]
[58]
Sørensen, M.A.; Andersen, V.L.; Hendel, H.W.; Vriamont, C.; Warnier, C.; Masset, J.; Huynh, T.H.V. Automated synthesis of 68 Ga/177 Lu-PSMA on the Trasis miniAllinOne. J. Labelled Comp. Radiopharm., 2020, 63(8), 393-403.
[http://dx.doi.org/10.1002/jlcr.3846] [PMID: 32374450]
[59]
Reverchon, J.; Khayi, F.; Roger, M.; Moreau, A.; Kryza, D. Optimization of the radiosynthesis of [68Ga]Ga-PSMA-11 using a Trasis MiniAiO synthesizer: Do we need to heat and purify? Nucl. Med. Commun., 2020, 41(9), 977-985.
[http://dx.doi.org/10.1097/MNM.0000000000001233] [PMID: 32796487]
[60]
Fuscaldi, L.L.; Sobral, D.V.; Durante, A.C.R.; Mendonça, F.F.; Miranda, A.C.C.; da Cunha, M.L.; Malavolta, L.; Mejia, J.; de Barboza, M.F. Standardization of the [68Ga]Ga-PSMA-11 radiolabeling protocol in an automatic synthesis module: Assessments for PET Imaging of Prostate Cancer. Pharmaceuticals, 2021, 14(5), 385.
[http://dx.doi.org/10.3390/ph14050385] [PMID: 33918987]
[61]
Wichmann, C.W.; Ackermann, U.; Poniger, S.; Young, K.; Nguyen, B.; Chan, G.; Sachinidis, J.; Scott, A.M. Automated radiosynthesis of [68Ga]Ga‐PSMA‐11 and [177Lu]Lu‐PSMA‐617 on the iPHASE MultiSyn module for clinical applications. J. Labelled Comp. Radiopharm., 2021, 64(3), 140-146.
[http://dx.doi.org/10.1002/jlcr.3889] [PMID: 33067810]
[62]
Meisenheimer, M.; Kürpig, S.; Essler, M.; Eppard, E. Manual vs automated 68 Ga-radiolabelling - A comparison of optimized processes. J. Labelled Comp. Radiopharm., 2020, 63(4), 162-173.
[http://dx.doi.org/10.1002/jlcr.3821] [PMID: 31845408]
[63]
European Directorate for the Quality of Medicines & Healthcare (EDQM) Gallium (68Ga) PSMA-11 Injection. Euro. Pharma., 2021, 3044, 1276-1277.
[64]
European Directorate for the Quality of Medicines & Healthcare (EDQM) Gallium (68Ga) PSMA-11 Injection. Euro. Pharma., 2022, 2482, 1274-1276.
[65]
European Directorate for the Quality of Medicines & Healthcare (EDQM) Gallium (68Ga) PSMA-11 Injection. Euro. Pharma., 2013, 2464, 1273-1274.
[66]
McCutchan, E.A. Nuclear data sheets for A = 68. Nucl. Data Sheets, 2012, 113(6-7), 1735-1870.
[http://dx.doi.org/10.1016/j.nds.2012.06.002]
[67]
CPMP/ICH/381/95-ICH harmonised tripartite guideline - Validation of analytical procedures: Text and methodology Q2(R1). 2014. Available from: CPMP/ICH/381/95 - ICH harmonised tripartite guideline (Accessed on: 27 Oct 2023)
[68]
Nader, M.; Herrmann, K.; Kunkel, F.; Zarrad, F.; Pacelli, A.; Fendler, W.; Koplin, S. Improved production of 68Ga-Pentixafor using cartridge mediated cation exchange purification. Appl. Radiat. Isot., 2022, 189, 110447.
[http://dx.doi.org/10.1016/j.apradiso.2022.110447] [PMID: 36087393]
[69]
Hörmann, A.A.; Plhak, E.; Klingler, M.; Rangger, C.; Pfister, J.; Schwach, G.; Kvaternik, H.; von Guggenberg, E. Automated Synthesis of 68Ga-Labeled DOTA-MGS8 and preclinical characterization of cholecystokinin-2 receptor targeting. Molecules, 2022, 27(6), 2034.
[http://dx.doi.org/10.3390/molecules27062034] [PMID: 35335396]
[70]
Plhak, E.; Pichler, C.; Dittmann-Schnabel, B.; Gößnitzer, E.; Aigner, R.M.; Stanzel, S.; Kvaternik, H. Automated synthesis of [68Ga]Ga-FAPI-46 on a Scintomics GRP Synthesizer. Pharmaceuticals, 2023, 16(8), 1138.
[http://dx.doi.org/10.3390/ph16081138] [PMID: 37631053]
[71]
Price, E.W.; Orvig, C. Matching chelators to radiometals for radiopharmaceuticals. Chem. Soc. Rev., 2014, 43(1), 260-290.
[http://dx.doi.org/10.1039/C3CS60304K] [PMID: 24173525]
[72]
Martin, R.; Weidlich, S.; Zerges, A-M.; Gameiro, C.; Lazarova, N.; Müllera, M. Fully automated synthesis of 68Ga-labelled peptides using the IBA Synthera® and Synthera® Extension modules. In: 18th ESRR- European Symposium on Radiopharmacy and Radiopharmaceuticals Conference; Salzburg, Austria, 2016; pp. 7-10.
[73]
Søborg Pedersen, K.; Baun, C.; Michaelsen Nielsen, K.; Thisgaard, H.; Ingemann Jensen, A.; Zhuravlev, F. Design, synthesis, computational, and preclinical evaluation of natTi/45Ti-labeled urea-based glutamate PSMA ligand. Molecules, 2020, 25(5), 1104.
[http://dx.doi.org/10.3390/molecules25051104] [PMID: 32131399]
[74]
Uğur, A.; Elçı̇, Ş.G.; Yüksel, D. Validation of HPLC method for the determination of chemical and radiochemical purity of a 68Ga-labelled EuK-Sub-kf-(3-iodo-y-) DOTAGA. Turk. J. Chem., 2021, 45(1), 26-34.
[http://dx.doi.org/10.3906/kim-2003-19] [PMID: 33679149]
[75]
Zhao, R.; Ploessl, K.; Zha, Z.; Choi, S.; Alexoff, D.; Zhu, L.; Kung, H.F. Synthesis and evaluation of 68 Ga- and 177 Lu-Labeled ( R )- vs ( S )-DOTAGA prostate-specific membrane antigen-targeting derivatives. Mol. Pharm., 2020, 17(12), 4589-4602.
[http://dx.doi.org/10.1021/acs.molpharmaceut.0c00777] [PMID: 33108189]
[76]
Green, M.A.; Hutchins, G.D.; Bahler, C.D.; Tann, M.; Mathias, C.J.; Territo, W.; Sims, J.; Polson, H.; Alexoff, D.; Eckelman, W.C.; Kung, H.F.; Fletcher, J.W. [68Ga]Ga-P16-093 as a PSMA-targeted pet radiopharmaceutical for detection of cancer: Initial evaluation and comparison with [68Ga]Ga-PSMA-11 in prostate cancer patients presenting with biochemical recurrence. Mol. Imaging Biol., 2020, 22(3), 752-763.
[http://dx.doi.org/10.1007/s11307-019-01421-7] [PMID: 31429050]
[77]
Lee, H.; Scheuermann, J.S.; Young, A.J.; Doot, R.K.; Daube-Witherspoon, M.E.; Schubert, E.K.; Fillare, M.A.; Alexoff, D.; Karp, J.S.; Kung, H.F.; Pryma, D.A. Preliminary Evaluation of 68Ga-P16-093, a PET radiotracer targeting prostate-specific membrane antigen in prostate cancer. Mol. Imaging Biol., 2022, 24(5), 710-720.
[http://dx.doi.org/10.1007/s11307-022-01720-6] [PMID: 35349040]
[78]
Wang, G.; Li, L.; Wang, J.; Zang, J.; Chen, J.; Xiao, Y.; Fan, X.; Zhu, L.; Kung, H.F.; Zhu, Z. Head-to-head comparison of [68Ga]Ga-P16-093 and 2-[18F]FDG PET/CT in patients with clear cell renal cell carcinoma: A pilot study. Eur. J. Nucl. Med. Mol. Imaging, 2023, 50(5), 1499-1509.
[http://dx.doi.org/10.1007/s00259-022-06101-3] [PMID: 36600099]
[79]
Wang, G.; Li, L.; Zang, J.; Hong, H.; Zhu, L.; Kung, H.F.; Zhu, Z. Head-to-head comparison of 68Ga-P16-093 and 68Ga-PSMA-617 PET/CT in patients with primary prostate cancer. Clin. Nucl. Med., 2023, 48(4), 289-295.
[http://dx.doi.org/10.1097/RLU.0000000000004566] [PMID: 36727866]
[80]
Wang, G.; Li, L.; Zhu, M.; Zang, J.; Wang, J.; Wang, R.; Yan, W.; Zhu, L.; Kung, H.F.; Zhu, Z. A prospective head-to-head comparison of [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11 PET/CT in patients with primary prostate cancer. Eur. J. Nucl. Med. Mol. Imaging, 2023, 50(10), 3126-3136.
[http://dx.doi.org/10.1007/s00259-023-06283-4] [PMID: 37233785]
[81]
Duan, X.; Cao, Z.; Zhu, H.; Liu, C.; Zhang, X.; Zhang, J.; Ren, Y.; Liu, F.; Cai, X.; Guo, X.; Xi, Z.; Pomper, M.G.; Yang, Z.; Fan, Y.; Yang, X. 68Ga-labeled ODAP-Urea-based PSMA agents in prostate cancer: First-in-human imaging of an optimized agent. Eur. J. Nucl. Med. Mol. Imaging, 2022, 49(3), 1030-1040.
[http://dx.doi.org/10.1007/s00259-021-05486-x] [PMID: 34453203]
[82]
Han, T.; Quan, Z.; Wang, M.; Meng, X.; Zhang, M.; Ye, J.; Li, G.; Wang, J.; Kang, F. Head-to-head comparison of 68 Ga-PSMA-11 with 68 Ga-P137 in patients with suspected prostate cancer. Mol. Pharm., 2023, 20(11), 5646-5654.
[http://dx.doi.org/10.1021/acs.molpharmaceut.3c00522]
[83]
Heo, Y.A. Flotufolastat F 18: Diagnostic first approval. Mol. Diagn. Ther., 2023, 27(5), 631-636.
[http://dx.doi.org/10.1007/s40291-023-00665-y] [PMID: 37439946]
[84]
Wurzer, A.; Di Carlo, D.; Schmidt, A.; Beck, R.; Eiber, M.; Schwaiger, M.; Wester, H.J. Radiohybrid ligands: A novel tracer concept exemplified by 18F- or 68GA-labeled rhPSMA inhibitors. J. Nucl. Med., 2020, 61(5), 735-742.
[http://dx.doi.org/10.2967/jnumed.119.234922] [PMID: 31862804]

Rights & Permissions Print Cite
Article Metrics
72
2
Wayfinder Image
© 2025 Bentham Science Publishers | Privacy Policy