Abstract
Purpose
[18F]ML-10 is the most advanced radiopharmaceutical for the clinical imaging of the apoptosis phenomenon by PET. The preparation of this radiopharmaceutical on a commercial radiosynthesis module and the requested quality controls for its release are presented herein.
Procedures
ML-10 as reference and its mesyloxy derivative as precursor for labelling with fluorine-18 were prepared. [18F]ML-10 was synthesized via a [18F]fluorine-de-mesyloxy aliphatic nucleophilic substitution via a GE TRACERLab® FX-FN module. Quality controls were performed.
Results
The labelling precursor was obtained in a four step synthesis in 28 % overall yield affording ML-10 in two steps (88 % yield). Pure [18F]ML-10 was obtained with a decay corrected yield of 39.8 % ± 8.4 % (n = 7) in 70 min and a specific activity of 235 ± 85 GBq/μmol at the end of synthesis.
Conclusions
[18F]ML-10 was prepared on a widely available automated module and passed the quality control. A LC/MS method was developed to measure specific radioactivity.
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References
Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9:231–241
Faust A, Hermann S, Wagner S et al (2009) Molecular imaging of apoptosis in vivo with scintigraphic and optical biomarkers—a status report. Anticancer Agents Med Chem 9:968–985
Blankenberg FG (2008) In vivo imaging of apoptosis. Cancer Biol Ther 7:1525–1532
Blankenberg FG (2008) In vivo detection of apoptosis [proceeding]. J Nucl Med 49(Suppl 2):81S–95S
De Saint-Hubert M, Prinsen K, Mortelmans L, Verbruggen A, Mottaghy FM (2009) Molecular imaging of cell death. Methods 48:178–187
Lahorte CM, Vanderheyden JL, Steinmetz N et al (2004) Apoptosis-detecting radioligands: current state of the art and future perspectives. Eur J Nucl Med Mol Imaging 31:887–919
Nguyen QD, Aboagye EO (2010) Imaging the life and death of tumors in living subjects: preclinical PET imaging of proliferation and apoptosis. Integr Biol (Cambridge) 2:483–495
Michalski MH, Chen X (2011) Molecular imaging in cancer treatment. Eur J Nucl Med Mol Imaging 38:358–377
Haberkorn U, Markert A, Mier W, Askoxylakis V, Altmann A (2011) Molecular imaging of tumor metabolism and apoptosis. Oncogene 30:4141–4151
Aboagye EO (2010) The future of imaging: developing the tools for monitoring response to therapy in oncology: the 2009 Sir James MacKenzie Davidson Memorial lecture [proceeding]. Br J Radiol 83:814–822
Reshef A, Shirvan A, Akselrod-Ballin A, Wall A, Ziv I (2010) Small-molecule biomarkers for clinical PET imaging of apoptosis. J Nucl Med 51:837–840
Cohen A, Shirvan A, Levin G et al (2009) From the Gla domain to a novel small-molecule detector of apoptosis. Cell Res 19:625–637
Reshef A, Shirvan A, Waterhouse RN et al (2008) Molecular imaging of neurovascular cell death in experimental cerebral stroke by PET. J Nucl Med 49:1520–1528
Hoglund J, Shirvan A, Antoni G et al (2011) 18F-ML-10, a PET tracer for apoptosis: first human study. J Nucl Med 52:720–725
Larson S (2010) Newsline, oncology. J Nucl Med 51:19N–25N
Mock B, Winkle W, Vavrek M (1997) A color spot test for the detection of Kryptofix 2.2.2 in [18F]FDG preparations. Nucl Med Biol 24:193–195
Klok RP, Windhorst AD (2006) Residual solvent analysis by gas chromatography in radiopharmaceutical formulations containing up to 12 % ethanol. Nucl Med Biol 33:935–938
Mahidhar YV, Rajesh M, Chaudhuri A (2004) Spacer-arm modulated gene delivery efficacy of novel cationic glycolipids: design, synthesis, and in vitro transfection biology. J Med Chem 47:3938–3948
Ziv I, Shirvan A (2005) NST Neurosurvival technologies Ltd. Perturbed membrane-binding compounds and methods of using the same [patent]. WO/2005/067388
Acknowledgements
We thank O. Tirel for performing the cyclotron irradiation. This work was supported by the “Région de Basse-Normandie” and the “Commissariat à l’énergie atomique et aux énergies alternatives” (CEA).
Conflict of Interest
The authors declare that they have no conflict of interest.
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Sobrio, F., Médoc, M., Martial, L. et al. Automated Radiosynthesis of [18F]ML-10, a PET Radiotracer Dedicated to Apoptosis Imaging, on a TRACERLab FX-FN Module. Mol Imaging Biol 15, 12–18 (2013). https://doi.org/10.1007/s11307-012-0574-y
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DOI: https://doi.org/10.1007/s11307-012-0574-y