Abstract
PET imaging at late time points post injection (p.i.) may allow tracer clearance from normal tissue and hence improve image contrast and detectability. 55Co is a promising isotope with high positron yield and a long half-life suitable for delayed time point imaging. Here, we compared the three radioconjugates [68Ga]Ga-DOTATATE, [64Cu]Cu-DOTATATE and [55Co]Co-DOTATATE by PET/CT imaging in NOD-SCID mice bearing subcutaneous somatostatin receptor expressing AR42J tumors. Methods: 55Co and 64Cu were produced by the 54Fe(d,n)55Co and 64Ni(p,n)64Cu nuclear reactions while 68Ga was obtained from a 68Ge/68Ga generator. 55Co and 64Cu were labeled with DOTATATE by heating in a sodium acetate buffer and HEPES buffer, respectively. AR42J tumor-bearing mice were PET/CT scanned dynamically 0-1 h p.i. For 64Cu and 55Co additional late time point imaging after 4 h p.i. and 24 h p.i. were also performed. Dose calculations were performed based on a known biodistrubution. The cumulated disintegrations in each organ were calculated by integration of a fitted exponential function to the biodistribution of each respective organ. Equivalent dose calculations were hereafter calculated by OLINDA/EXM using the MIRD formalism. Results: Tumor uptake was rapid from 0 h p.i. to 1 h p.i. for all three radioconjugates. Normal tissue ratios as represented by tumor/liver, tumor/kidney and tumor/muscle ratios increased significantly over time with [55Co]Co-DOTATATE reaching the highest ratio of all radioconjugates. For [55Co]Co-DOTATATE, the tumor-to-liver ratio increased to 65±16 at 4 h and 50±6 at 24 h, which were 15 (p<0.001) and 30 (p<0.001) times higher, respectively, than the corresponding ratios for [64Cu]Cu-DOTATATE and 5 (p<0.001) times higher than that of [68Ga]Ga-DOTATATE at 1 h p.i. Correspondingly, tumor/kidney and tumor/muscle ratios for [55Co]Co-DOTATATE were 4 (p<0.001) and 11 (p<0.001) times higher than that of [64Cu]Cu-DOTATATE at 24 h p.i. An equivalent dose was calculated to 9.6E-02 mSv/MBq for [55Co]Co-DOTATATE. Conclusion: [55Co]Co-DOTATATE demonstrated superior image contrast compared to [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE for PET imaging of somatostatin receptor expressing tumors, warranting translation into clinical trials. Dosimetry calculations found comparable effective doses for [55Co]Co-DOTATATE compared to both [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE.
- Animal Imaging
- Molecular Imaging
- Oncology: Endocrine
- <sup>55</sup>Co
- <sup>64</sup>Cu
- <sup>68</sup>Ga
- DOTATATE
- Neuroendocrine tumor
- Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.