Cyclotron Production of High–Specific Activity ⁵⁵ Co and In Vivo Evaluation of the Stability of ⁵⁵ Co 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 1.96GBq/µmol. 55Co-DO3A and 55Co-NO2A peptide complexes were radiolabelled at 3.7MBq/µg and injected into HCT-116 tumor xenografted mice. PET imaging and biodistribution studies were performed at 24 and 48 hours post injection and compared with that of 55CoCl2. Both 55Co-metal-chelate complexes demonstrated good in vivo stability by reducing the radiotracers’ uptake in the liver by 6-fold at 24 with ~1% ID/g and at 48 hours with ~0.5% ID/g, and reducing uptake in the heart by 4-fold at 24 hours with ~0.7% ID/g and 7-fold at 48 hours with ~0.35% ID/g. These results support the use of 55Co as a promising new radiotracer for Positron Emission Tomography (PET) imaging of cancer and other diseases.

Radiometals for imaging and theranostics, current production, and future perspectives

“…While less studied than some of the other radiometals discussed, 55 Co ( T 1/2 = 17.5 h) offers slightly different chemistry and the potential for better in vivo stability than some of the radiocopper analogues . 55 Co has also been used for imaging in the form of a simple metal salt to study various disease processes …”

“…The production and purification of 55 Co is typically via the 58 Ni(p,α) 55 Co reaction and follows similar chemistry to the production of 64 Cu . Natural Ni target foils or targets prepared with enriched 58 Ni electroplated on copper, gold, or silver backings are irradiated with proton energies of 10 to 15 MeV . While the cross section for 55 Co is higher at higher energies, typically the irradiation of targets is carried out at lower proton energies to minimize the production of 57 Co, which is produced either directly by the 60 Ni(p,α) 57 Co reaction when using Ni targets of natural composition or from the decay of 57 Ni that is produced via the 58 Ni(p,pn) 57 Ni reaction.…”

“…135,136 Natural Ni target foils or targets prepared with enriched 58 Ni electroplated on copper, gold, or silver backings are irradiated with proton energies of 10 to 15 MeV. 130,135,137 While the cross section for 55 Co is higher at higher energies, 138 typically the irradiation of targets is carried out at lower proton energies to minimize the production of 57 Co, which is produced either directly by the 60 Ni(p,α) 57 Co reaction when using Ni targets of natural composition or from the decay of 57 Ni that is produced via the 58 Ni(p,pn) 57 Ni reaction. The purification procedures for 55 Co produced using Ni targets are typically similar to those employed for 64 Cu.…”

PET radiometals for antibody labeling

“…The radionuclide 66 Ga (t 1/2 = 9.3 hours, 56.5% β + , E β + ave = 1750 keV, 43.5% EC; Figure 8 and Table 1) constitutes an intriguing alternative to 67 Ga (t 1/2 = 78.3 hours) and 68 Ga (t 1/2 = 68.3 minutes), which are used for SPECT and PET imaging, respectively. 84 Particularly, the relatively long half-life of 66 Ga makes it a more practical radiolabel for antibodies and proteins, whose slower invivo kinetics are poorly matched by the much shorter half-life of 68 Ga.…”

“…In instances where the conventional isotopes do not suit the desired application, other interesting radionuclides have been investigated which offer more appropriate chemical or decay properties. Notable examples of such attractive radionuclides include 52 Mn, 55 Co, 152 Tb, 90 Nb, 66 Ga, 72 As, and 69 Ge. The utilization of these relatively long-lived PET isotopes often requires the leveraging of inorganic metal complexation chemistry with bifunctional chelators (BFCs) containing both a polydentate radiometal ligand and a bioconjugation functional group.…”