Production, Purification, and Applications of a Potential Theranostic Pair: Cobalt-55 and Cobalt-58m

Abstract

The emerging success of [68Ga/177Lu]Ga/Lu-DOTATATE as a theranostic pair has spurred interest in other isotopes as potential theranostic combinations. Here, we review cobalt-55 and cobalt-58m as a potential theranostic pair. Radionuclidically pure cobalt-55 and cobalt-58m have been produced on small cyclotrons with high molar activity. In vitro, DOTATOC labeled with cobalt has shown greater affinity for SSTR2 than DOTATOC labeled with gallium and yttrium. Similarly, [58mCo]Co-DOTATATE has shown improved cell-killing capabilities as compared to DOTATATE labeled with either indium-111 or lutetium-177. Finally, PET imaging with an isotope such as cobalt-55 allows for image acquisition at much later timepoints than gallium, allowing for an increased degree of biological clearance of non-bound radiotracer. We discuss the accelerator targetry and radiochemistry used to produce cobalt-55,58m, emphasizing the implications of these techniques to downstream radiotracers being developed for imaging and therapy.

Radiolabeling Diaminosarcophagine with Cyclotron-Produced Cobalt-55 and [55Co]Co-NT-Sarcage as a Proof of Concept in a Murine Xenograft Model

“…14,18 Despite Sar synthesis procedures typically beginning with Co-ethylenediamine complexation, 19−25 we have not found prior reports of labeling Co to uncoordinated Sar complexes in no-carrier-added conditions. Most Co-radiopharmaceuticals have stabilized Co via 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) 9,14,26 and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). 10,11,14,26,27 NOTA can be radiolabeled with Co at room temperature and pH = 4−7, whereas DOTA typically requires additional heating.…”

“…12−17 Cobalt-55 can also serve as a diagnostic congener for 58m Co (t 1/2 = 9.10 h, IC = 100%), a low-energy electron-emitting radionuclide that holds promise for treating small metastatic disease due to its potential to reduce radiation dose to off-target tissues. 14,18 Despite Sar synthesis procedures typically beginning with Co-ethylenediamine complexation, 19−25 we have not found prior reports of labeling Co to uncoordinated Sar complexes in no-carrier-added conditions. Most Co-radiopharmaceuticals have stabilized Co via 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) 9,14,26 and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).…”

“…Cobalt-55 ( t 1/2 = 17.53 h, I β+ = 77%) is quantifiable with positron emission tomography (PET) imaging − and has demonstrated significant potential in preclinical oncology research. − Cobalt-55 can also serve as a diagnostic congener for 58m Co ( t 1/2 = 9.10 h, IC = 100%), a low-energy electron-emitting radionuclide that holds promise for treating small metastatic disease due to its potential to reduce radiation dose to off-target tissues. , Despite Sar synthesis procedures typically beginning with Co-ethylenediamine complexation, − we have not found prior reports of labeling Co to uncoordinated Sar complexes in no-carrier-added conditions. Most Co-radiopharmaceuticals have stabilized Co via 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) ,, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). ,,,, NOTA can be radiolabeled with Co at room temperature and pH = 4–7, whereas DOTA typically requires additional heating.…”

“…Cobalt-55 ( t 1/2 = 17.53 h, I β+ = 77%) is quantifiable with positron emission tomography (PET) imaging − and has demonstrated significant potential in preclinical oncology research. − Cobalt-55 can also serve as a diagnostic congener for 58m Co ( t 1/2 = 9.10 h, IC = 100%), a low-energy electron-emitting radionuclide that holds promise for treating small metastatic disease due to its potential to reduce radiation dose to off-target tissues. , Despite Sar synthesis procedures typically beginning with Co-ethylenediamine complexation, − we have not found prior reports of labeling Co to uncoordinated Sar complexes in no-carrier-added conditions. Most Co-radiopharmaceuticals have stabilized Co via 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) ,, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). ,,,, NOTA can be radiolabeled with Co at room temperature and pH = 4–7, whereas DOTA typically requires additional heating. In comparison to NOTA and DOTA, Co-Sar stability/formation constants have not been measured due to their high kinetic inertness, which makes Sar and Sar-derivatives interesting as stabilizers for Co. Additionally, the process to remove Co from Co-Sar complexes requires such stringent conditions that concentrated hydrochloric acid alone is insufficient to fully degrade the complex. , Given the high stability of Co-Sar complexes in vitro and in vivo, , along with recent studies highlighting unique biological applications of Co-Sar derivatives in vitro, functionalized Sar compounds could therefore potentially be developed into promising Co-based radiopharmaceuticals.…”

“…Most Co-radiopharmaceuticals have stabilized Co via 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) 9,14,26 and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). 10,11,14,26,27 NOTA can be radiolabeled with Co at room temperature and pH = 4−7, whereas DOTA typically requires additional heating. In comparison to NOTA and DOTA, Co-Sar stability/formation constants have not been measured due to their high kinetic inertness, 25 which makes Sar and Sar-derivatives interesting as stabilizers for Co. Additionally, the process to remove Co from Co-Sar complexes requires such stringent conditions that concentrated hydrochloric acid alone is insufficient to fully degrade the complex.…”