Improving Contrast and Detectability: Imaging with [⁵⁵Co]Co-DOTATATE in Comparison with [⁶⁴Cu]Cu-DOTATATE and [⁶⁸Ga]Ga-DOTATATE.

Abstract

PET imaging at late time points after injection 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 imaging at delayed time points. Here, we compared the 3 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. <b>Methods:</b>⁵⁵Co and ⁶⁴Cu were produced by the ⁵⁴Fe(d,n)⁵⁵Co and ⁶⁴Ni(p,n)⁶⁴Cu nuclear reactions, whereas ⁶⁸Ga was obtained from a ⁶⁸Ge/⁶⁸Ga generator. ⁵⁵Co and ⁶⁴Cu were labeled with DOTATATE by heating in a sodium acetate buffer and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer, respectively. AR42J tumor-bearing mice were dynamically scanned 0-1 h after injection. For ⁶⁴Cu and ⁵⁵Co, additional imaging was also performed at late time points after 4 and 24 h. Dose calculations were based on a known biodistribution. The cumulated disintegrations in each organ were calculated by integration of a fitted exponential function to the biodistribution of each respective organ. Equivalent doses were calculated by OLINDA/EXM using the MIRD formalism. <b>Results:</b> Tumor uptake was rapid from 0 to 1 h after injection for all 3 radioconjugates. Normal-tissue ratios as represented by tumor-to-liver, tumor-to-kidney, and tumor-to-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 (<i>P</i> < 0.001) and 30 (<i>P</i> < 0.001) times higher, respectively, than the corresponding ratios for [⁶⁴Cu]Cu-DOTATATE and 5 (<i>P</i> < 0.001) times higher than that of [⁶⁸Ga]Ga-DOTATATE at 1 h. Correspondingly, tumor-to-kidney and tumor-to-muscle ratios for [⁵⁵Co]Co-DOTATATE were 4 (<i>P</i> < 0.001) and 11 (<i>P</i> < 0.001) times higher than that of [⁶⁴Cu]Cu-DOTATATE at 24 h. An equivalent dose was calculated as 9.6E-02 mSv/MBq for [⁵⁵Co]Co-DOTATATE. <b>Conclusion:</b> [⁵⁵Co]Co-DOTATATE demonstrated superior image contrast compared with [⁶⁴Cu]Cu-DOTATATE and [⁶⁸Ga]Ga-DOTATATE for PET imaging of somatostatin receptor-expressing tumors, warranting translation into clinical trials. Dosimetry calculations found that effective doses for [⁵⁵Co]Co-DOTATATE were comparable to those for both [⁶⁴Cu]Cu-DOTATATE and [⁶⁸Ga]Ga-DOTATATE.