68Ga-DATATOC: synthesis, radiolabeling, and first in vivo studies


68Ga-DATATOC: synthesis, radiolabeling, and first in vivo studies

Waldron, B.; Seemann, J.; Bergmann, R.; Nagel, J.; Rösch, F.; Sinnes, J. P.

Objectives: 68Ga-DOTATOC is currently used as the industry standard for diagnostic imaging of NETs and its metastases. Radiolabeling can be performed manually and automated at 95°C. In order to approach the application of 68Ga following a kit-type procedure, a DATA-based chelator (6-amino-1,4-diazepine-triacetate) was used in the study as it has shown to radiolabel under very mild conditions. Conjugation with TOC to afford a DOTATOC analog may enable radiolabeling of the peptide at room temperature.
Methods: DATATOC was synthesized in a seven-step synthesis. Radiolabeling with 68Ga was performed manually at room temperature, and stability was assessed in human serum. An automated setup was also examined, using the Modular-Lab eazy (Eckert & Ziegler, Berlin, Germany). First in vivo studies using MPC-mCherry tumor–bearing mice were performed and compared with DOTATATE.
Research: Radiolabeling was performed at room temperature using N2 solution, NaOAc buffer, and 14 nmol DATATOC. An RCY of 96.3% ± 1.2% was obtained within 3 min. Stability was tested in human serum over a period of 2 h (Δ, 1.3%). Automated labeling with a 23 nmol precursor achieved quantitative complexation of 68Ga. In vivo PET/CT studies with 68Ga-DATATOC indicate a high specific uptake in the tumor region after 10 min (SUV of 3.73 ± 1.49). In a blocking study with OC, the SUV in the tumor was reduced to 0.45 ± 0.15. In addition, 68Ga-DATATOC showed high stability in mouse plasma with 93.7% of the tracer remaining intact after 120 min. Compared with 68Ga-DOTATATE a faster renal excretion of the tracer was observed.
Conclusion: DATATOC can be labeled with 68Ga in a manual or automated setup rapidly at room temperature, offering significant advantages over similar DOTA-based derivatives. Furthermore, first in vivo studies confirm excellent targeting and excretion characteristics for the novel tracer. With the perspective toward a kit-type formulation, the superior characteristics of this new compound pave the way for a new generation of 68Ga radiopharmaceuticals.

  • Abstract in refereed journal
    Journal of Nuclear Medicine 56(2015)2, 27
    DOI: 10.2967/jnm565abs
  • Lecture (Conference)
    3rd Theranostics World Congress (3TWC) on Gallium-68 and PRRT, 12.-14.03.2015, Baltimore, USA

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Publ.-Id: 22759