Cyclotron Production of High-Specific Activity 55Co and In Vivo Evaluation of the Stability of 55Co Metal-Chelate-Peptide Complexes

Abstract

This work describes the production of high-specific activity 55Co and the evaluation of the stability of 55Co-metal-chelate-peptide complexes in vivo. 55Co was produced via the 58Ni(p,α)55Co reaction and purified using anion exchange chromatography with an average recovery of 92% and an average specific activity of 1.96 GBq/μmol. 55Co-DO3A and 55Co-NO2A peptide complexes were radiolabeled at 3.7 MBq/μg and injected into HCT-116 tumor xenografted mice. Positron emission tomography (PET) and biodistribution studies were performed at 24 and 48 hours postinjection and compared to those of 55CoCl2. Both 55Co-metal-chelate complexes demonstrated good in vivo stability by reducing the radiotracers' uptake in the liver by sixfold at 24 hours with ~ 1% ID/g and at 48 hours with ~ 0.5% ID/g and reducing uptake in the heart by fourfold at 24 hours with ~ 0.7% ID/g and sevenfold at 48 hours with ~ 0.35% ID/g. These results support the use of 55Co as a promising new radiotracer for PET imaging of cancer and other diseases.

Figure 1

Concentration of ⁵⁵Co and ⁵⁷Ni in each fraction, as measured using HPGe detection of the characteristic gamma rays, showing good separation.

Figure 2

⁵⁵Co-DOTA titration curves demonstrating a seven-fold increase in ESA (259 MBq/µmol to 1.96 GBq/µmol) when washing the column with an additional 40 mL 9 M HCl acid versus a 10 mL column wash.

Figure 3

24 and 48 hr PET images of ⁵⁵CoCl₂ showing uptake in the tumor and clearance through the liver, kidney, and intestines (A). Tumor-to-blood ratio exhibits a 3-fold increase from 2–48 hrs (B).

Figure 4

Comparison of the 24 hr (A) and 48 hr (B) biodistributions of ⁵⁵CoCl₂ with ⁵⁵Co-NO2A-FDNB and ⁵⁵Co-DO3A-FDNB exhibiting the in vivo stability of ⁵⁵Co-NO2A and ⁵⁵Co-DO3A complexes.