Theranostische Liganden: Aktuelle und zukünftige Anwendungen

Zusammenfassung

Theranostische Liganden sind niedermolekulare oder Träger-gebundene Radiopharmaka, die sowohl in der bildgebenden Diagnostik als auch in der Radionuklidtherapie überwiegend zur Behandlung verschiedener Tumorentitäten eingesetzt werden.

Eine Vielzahl theranostischer Radiopharmaka, wie bspw. ¹⁷⁷Lu-DOTATATE für die Peptid-Radiorezeptor-Therapie (PRRT), werden bereits erfolgreich klinisch eingesetzt. Weitere Liganden werden in Zukunft Einzug in die klinische Routine halten und möglicherweise neue therapeutische Optionen für Patienten mit Tumorerkrankungen bieten.

Ziel dieses Übersichtsartikels ist es, die Wertigkeit der theranostischen Liganden als Behandlungsmöglichkeit bei Patienten mit fortgeschrittenen Tumorerkrankungen darzustellen. Des Weiteren soll ein Überblick über zukünftige therapeutische Anwendungsmöglichkeiten verschiedener neuer Liganden und Radioisotope gegeben werden.

Abstract

Radiotheranostics are small-molecule or carrier-bound radiopharmaceuticals that can be used for diagnostic imaging and radionuclide therapy, especially for the treatment of various tumour diseases.

Several theranostic ligands, including ¹⁷⁷Lu-DOTATATE for peptide radioreceptor therapy (PRRT) were successfully translated to the clinic. Novel ligands are expected to enter clinical routine in the near future and may offer new therapeutic options for patients with cancer.

We aim to review the current and future value of radiotheranostics as management option for patients with advanced cancer. Furthermore, an overview of future therapeutic applications of novel ligands and radioisotopes will be given.

Schlüsselwörter

theranostische Liganden - PRRT - ¹⁷⁷Lu-DOTATATE - ¹⁷⁷Lu-PSMA

Key words

radiotheranostics - PRRT - ¹⁷⁷Lu-DOTATATE - ¹⁷⁷Lu-PSMA

Publication History

Article published online:
29 November 2021

• Literatur

• 1 Luster M, Clarke SE, Dietlein M. et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2008; 35: 1941-1959
• 2 Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994; 97: 418-428
• 3 Sartor O, de Bono J, Chi KN. et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2021; DOI: 10.1056/NEJMoa2107322.
• 4 Schulz J, Rohracker M, Stiebler M. et al. Proof of Therapeutic Efficacy of a (177)Lu-Labeled Neurotensin Receptor 1 Antagonist in a Colon Carcinoma Xenograft Model. J Nucl Med 2017; 58: 936-941
• 5 Sherman M, Levine R. Nuclear Medicine and Wall Street: An Evolving Relationship. J Nucl Med 2019; 60 (Suppl. 02) 20S-24S
• 6 Dolgin E. Radioactive drugs emerge from the shadows to storm the market. Nat Biotechnol 2018; 36: 1125-1127
• 7 Schaffert S, Herrmann K. A Conversation Between Susanne Schaffert and Ken Herrmann. J Nucl Med 2019; 60: 875-878
• 8 Herrmann K, Schwaiger M, Lewis JS. et al. Radiotheranostics: a roadmap for future development. Lancet Oncol 2020; 21: e146-e156
• 9 Banerjee S, Pillai MR, Knapp FF. Lutetium-177 therapeutic radiopharmaceuticals: linking chemistry, radiochemistry, and practical applications. Chem Rev 2015; 115: 2934-2974
• 10 Fahey FH, Grant FD, Thrall JH. Saul Hertz, MD, and the birth of radionuclide therapy. EJNMMI Phys 2017; 4: 15
• 11 Hertz B. A tribute to Dr. Saul Hertz: The discovery of the medical uses of radioiodine.. World J Nucl Med 2019; 18: 8-12
• 12 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 (Suppl. 02) 3S-9S
• 13 Rudisile S, Gosewisch A, Wenter V. et al. Salvage PRRT with (177)Lu-DOTA-octreotate in extensively pretreated patients with metastatic neuroendocrine tumor (NET): dosimetry, toxicity, efficacy, and survival. BMC Cancer 2019; 19: 788
• 14 Strosberg J, El-Haddad G, Wolin E. et al. Phase 3 Trial of (177)Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med 2017; 376: 125-135
• 15 Strosberg J, Wolin E, Chasen B. et al. Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With (177)Lu-Dotatate in the Phase III NETTER-1 Trial. J Clin Oncol 2018; 36: 2578-2584
• 16 Marinova M, Mucke M, Fischer F. et al. Quality of life in patients with midgut NET following peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 2019; 46: 2252-2259
• 17 Rahbar K, Boegemann M, Yordanova A. et al. PSMA targeted radioligandtherapy in metastatic castration resistant prostate cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective analysis of overall survival.. Eur J Nucl Med Mol Imaging 2018; 45: 12-19
• 18 Hofman MS, Violet J, Hicks RJ. et al. [(177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol 2018; 19: 825-833
• 19 Jacob M, Chang L, Pure E. Fibroblast activation protein in remodeling tissues. Curr Mol Med 2012; 12: 1220-1243
• 20 Kelly T, Huang Y, Simms AE. et al. Fibroblast activation protein-alpha: a key modulator of the microenvironment in multiple pathologies. Int Rev Cell Mol Biol 2012; 297: 83-116
• 21 Loktev A, Lindner T, Mier W. et al. A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts. J Nucl Med 2018; 59: 1423-1429
• 22 Langbein T, Weber WA, Eiber M. Future of Theranostics: An Outlook on Precision Oncology in Nuclear Medicine. J Nucl Med 2019; 60 (Suppl. 02) 13S-19S
• 23 Kessler L, Kupusovic J, Ferdinandus J. et al. Visualization of Fibroblast Activation After Myocardial Infarction Using ⁶⁸Ga-FAPI PET. Clinical Nuclear Medicine 2021; DOI: 10.1097/RLU.0000000000003745.
• 24 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
• 25 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
• 26 Lindner T, Altmann A, Kramer S. et al. Design and Development of (99m)Tc-Labeled FAPI Tracers for SPECT Imaging and (188)Re Therapy. J Nucl Med 2020; 61: 1507-1513
• 27 Kessler L, Ferdinandus J, Hirmas N. et al. Ga-68-FAPI as diagnostic tool in sarcoma: Data from the FAPI-PET prospective observational trial. J Nucl Med 2021; DOI: 10.2967/jnumed.121.262096.
• 28 Kratochwil C, Giesel FL, Rathke H. et al. [(153)Sm]Samarium-labeled FAPI-46 radioligand therapy in a patient with lung metastases of a sarcoma. Eur J Nucl Med Mol Imaging 2021; 48: 3011-3013
• 29 Morgat C, Mishra AK, Varshney R. et al. Targeting neuropeptide receptors for cancer imaging and therapy: perspectives with bombesin, neurotensin, and neuropeptide-Y receptors. J Nucl Med 2014; 55: 1650-1657
• 30 Schulz J, Rohracker M, Stiebler M. et al. Comparative Evaluation of the Biodistribution Profiles of a Series of Nonpeptidic Neurotensin Receptor-1 Antagonists Reveals a Promising Candidate for Theranostic Applications. J Nucl Med 2016; 57: 1120-1123
• 31 Baum RP, Singh A, Schuchardt C. et al. (177)Lu-3BP-227 for Neurotensin Receptor 1-Targeted Therapy of Metastatic Pancreatic Adenocarcinoma: First Clinical Results. J Nucl Med 2018; 59: 809-814
• 32 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
• 33 Fani M, Braun F, Waser B. et al. Unexpected sensitivity of sst2 antagonists to N-terminal radiometal modifications. J Nucl Med 2012; 53: 1481-1489
• 34 Nicolas GP, Schreiter N, Kaul F. et al. Sensitivity Comparison of (68)Ga-OPS202 and (68)Ga-DOTATOC PET/CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Phase II Imaging Study. J Nucl Med 2018; 59: 915-921
• 35 Albrecht J, Exner S, Grotzinger C. et al. Multimodal Imaging of 2-Cycle PRRT with (177)Lu-DOTA-JR11 and (177)Lu-DOTATOC in an Orthotopic Neuroendocrine Xenograft Tumor Mouse Model. J Nucl Med 2021; 62: 393-398
• 36 Feuerecker B, Tauber R, Knorr K. et al. Activity and Adverse Events of Actinium-225-PSMA-617 in Advanced Metastatic Castration-resistant Prostate Cancer After Failure of Lutetium-177-PSMA. Eur Urol 2021; 79: 343-350
• 37 Kratochwil C, Giesel FL, Bruchertseifer F. et al. (2)(1)(3)Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience. Eur J Nucl Med Mol Imaging 2014; 41: 2106-2119
• 38 Ahmadzadehfar H, Essler M. It is time to move forward into the era of Theranostics. EJNMMI Res 2018; 8: 9