⁶⁸Ga-Radiopharmaka: Methode oder Episode?

⁶⁸Ga macht seit einiger Zeit eine steile Karriere in Radiopharmazie und klinischer PET und hat für einige Krankheitsbilder das Patientenmanagement erheblich beeinflusst. Wird dieser Boom anhalten?

The nuclide properties of Gallium-68 are less favorable than those of 18F. However, in most instances, the labeling procedures of ⁶⁸Ga are more robust and rapid as compared to 18F chemistry. Like 99 mTc, ⁶⁸Ga is obtained from radionuclide generators. Hence, ⁶⁸Ga-radiopharmaceuticals can be synthesized independently from an on-site cyclotron. ⁶⁸Ge / ⁶⁸Ga-generators are considered pharmaceuticals and require an approval by the BfArM in order to be used for patient care. Although currently, ⁶⁸Ga tracers are mostly synthesized using robotics, kit synthesis are feasible if approved generators are used. Some kits have been approved recently, and more will follow. Using a cyclotron, much larger amounts of 18F-tracers can be produced in a single batch as compared to ⁶⁸Ga-tracers, which is why a single dose of a 18F radiopharmaceutical comes at a much lower price. Hence, for blockbuster applications, ⁶⁸Ga-radiopharmaceuticals will ultimately be replaced by their 18F analogs. This, however, only applies as long as ⁶⁸Ga cannot be produced in similar amounts and efficiency using cyclotrons. Somatostatin receptor PET with ⁶⁸Ga radiopharmaceuticals represents a stronghold in management of neuroendocrine tumors, which will be further strengthened in light of the approval of respective ⁶⁸Ga-labeling kits for SSTR ligands. ⁶⁸Ga-PSMA-PET diagnostics of prostate carcinoma is a major breakthrough for dissemination and wide application of ⁶⁸Ga radiopharmaceuticals. It is anticipated that several ⁶⁸Ga-PSMA-tracers will obtain a marketing authorization soon. Further ⁶⁸Ga-tracers are currently being evaluated and show promising results, but their clinical value will have to be proven in prospective studies.

Schlüsselwörter

Gallium-68 - Radionuklidgeneratoren - Positronenemissionstomografie - Neuroendokrine - Tumoren - Prostatakarzinom

• Literatur

• 1 Levine R, Krenning EP.. Clinical History of the Theranostic Radionuclide Approach to Neuroendocrine Tumors and Other Types of Cancer: Historical Review Based on an Interview of Eric P. Krenning by Rachel Levine. J Nucl Med 2017; 58: 3S-9S
• 2 Lütje S, Slavik R, Fendler W. et al. PSMA ligands in prostate cancer - Probe optimization and theranostic applications. Methods 2017; 130: 42-50
• 3 Walenkamp AME, Lapa C, Herrmann K. et al. CXCR4 Ligands: The Next Big Hit? J Nucl Med 2017; 58: 77S-82S
• 4 Notni J, Wester HJ.. Re-thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals. J Label Compd Radiopharm 2018; 61: 141-153
• 5 Lin M, Waligorski GJ, Lepera CG.. Production of Curie quantities of ⁶⁸Ga with a medical cyclotron via the ⁶⁸Zn(p, n)⁶⁸Ga reaction. Appl Rad Isot 2018; 133: 1-3
• 6 Šimeček J, Hermann P, Wester HJ. et al. How is ⁶⁸Ga-labelling of macrocyclic chelators influenced by metal ion contaminants in ⁶⁸Ge / ⁶⁸Ga generator eluates? ChemMedChem 2013; 8: 95-103
• 7 Hacht B.. Gallium (III) ion hydrolysis under physiological conditions. Bull Korean Chem Soc 2008; 29: 372-376
• 8 Uchida M, Okuwaki A.. Potentiometric determination of the first hydrolysis constant of gallium(III) in NaCl solution to 100 °C. J Sol Chem 1998; 27: 965-978
• 9 Tsionou MI, Knapp CE, Foley CA. et al. Comparison of macrocyclic and acyclic chelators for gallium-⁶⁸radiolabelling. RSC Adv 2017; 7: 49586
• 10 Beheshti M, Paymani Z, Brilhante J. et al. Optimal time-point for Ga-⁶⁸-PSMA-11 PET / CT imaging in assessment of prostate cancer: feasibility of sterile cold-kit tracer preparation? Eur J Nucl Med Mol Imaging 2018; 45: 1188-1196
• 11 Ginj M, Zhang H, Waser B. et al. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proc Natl Acad Sci U S A 2006; 103: 16436-16441
• 12 Nicolas GP, Schreiter N, Kaul F. et al. Sensitivity Comparison of ⁶⁸Ga-OPS202 and ⁶⁸Ga-DOTATOC PET / CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Phase II Imaging Study. J Nucl Med 2018; 59: 915-921
• 13 Kulkarni HR, Singh A, Schuchardt C. et al. PSMA-Based Radioligand Therapy for Metastatic Castration-Resistant Prostate Cancer: The Bad Berka Experience Since 2013. J Nucl Med 2016; 57: 97S-104S
• 14 Fendler WP, Eiber M, Beheshti M. et al. ⁶⁸Ga-PSMA PET / CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging 2017; 44: 1014-1024
• 15 Wurzer A, Seidl C, Morgenstern A. et al. Dual-Nuclide Radiopharmaceuticals for Positron Emission Tomography Based Dosimetry in Radiotherapy. Chem Eur J 2018; 24: 547-550
• 16 Wester HJ, Keller U, Schottelius M. et al. Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging. Theranostics 2015; 5: 618-630
• 17 Philipp-Abbrederis K, Herrmann K, Knop S. et al. In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma. EMBO Mol Med 2015; 7: 477-487
• 18 Reubi JC, Wenger S, Schmuckli-Maurer J. et al. Bombesin receptor subtypes in human cancers: detection with the universal radioligand (125)I-[D-TYR(6), beta-ALA(11), PHE (13), NLE(14)] bombesin(6-14). Clin Cancer Res 2002; 8: 1139-1146
• 19 Minamimoto R, Sonni I, Hancock S. et al. Prospective Evaluation of ⁶⁸Ga-RM2 PET / MRI in Patients with Biochemical Recurrence of Prostate Cancer and Negative Findings on Conventional Imaging. J Nucl Med 2018; 59: 803-808
• 20 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
• 21 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
• 22 Loktev A, Lindner T, Mier W. et al. A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts. J Nucl Med 2018; 59: 1423-1429
• 23 Giesel F, Kratochwil C, Lindner T. et al. FAPI-PET / CT: biodistribution and preliminary dosimetry estimate of two DOTAcontaining FAP-targeting agents in patients with various cancers. J Nucl Med 2018 : DOI: 10.2967/jnumed. 118.215913 [Epub ahead of print]