Radiosynthesis of ⁵⁵Co‐ and ^58mCo‐labelled DOTATOC for positron emission tomography imaging and targeted radionuclide therapy

Abstract

The SPECT compound 57 Co-DOTATOC has recently been shown to have the highest affinity ever found for somatostatin receptor subtype 2. Moreover, the internalization rate into the tumour cell line AR42J was also the highest found for any somatostatin-based radiopharmaceutical. We here present a method to prepare the positron emission tomography compound 55 Co-DOTATOC as a new promising radiopharmaceutical for positron emission tomography via solid target irradiations of enriched Fe-metal. Also, the new, potent Auger-electron-emitting radioisotope 58mCo and the resulting therapeutic compound 58m Co-DOTATOC as candidate for targeted radionuclide therapy of somatostatin receptor-positive tumours have been prepared with high yield and high radiochemical purity.

Cyclotron production and radiochemical separation of 55Co and 58mCo from 54Fe, 58Ni and 57Fe targets

“…Comparing the separation chemistry methods of this work with previously reported methods (Mastren et al, 2015; Sharma et al, 1986; Spellerberg et al, 1998; Thisgaard et al, 2011a, 2011b, 2014; Zaman et al, 2003) there are many improvements. First, more than 99.99% of the co-produced 52 Mn from 54 Fe(d,a) was removed from the separated 55 Co; second, more than 95% of the produced 55 Co, decay corrected to EoB, in either 58 Ni or 54 Fe targets was isolated at a very high concentration in ≤ 600 μL, which is volume that can be easily evaporated for reconstitution in any desired volume of any desired acid or buffered solution; and third, the effective specific activities of 55 Co and 58m Co toward established chelators are comparable to the highest ones that have been reported in the literature.…”

“…Cobalt-55 ( t 1/2 = 17.53 h, 76% β + , E max = 1498 keV) is an intermediate-lived positron-emitting radionuclide that is a useful radiotracer for positron emission tomography (PET) (De Reuck et al, 2004, 1999; Jansen et al, 1997a, 1997b, 1994, 1996b, 1995; Korf et al, 1998; Stevens et al, 1999) and particularly useful for labeling proteins due to its favorable complexation with established bifunctional chelators (Dam et al, 2016; Garousi et al, 2017; Mastren et al, 2015; Srivastava et al, 1994; Thisgaard et al, 2011b; Wallberg et al, 2010). Furthermore, when chelated in oxidation state 3+, the formed complex is considered inert (Duckworth et al, 2009; Regoeczi et al, 1995; Wegner and Spatz, 2013) and therefore it is less prone to interact with ligands in blood plasma and non-targeted organs due to trans-chelation.…”

“…So far, only seven studies have followed this chelator-based approach (Dam et al, 2016; Garousi et al, 2017; Goethals et al, 2000; Mastren et al, 2015; Srivastava et al, 1994; Thisgaard et al, 2011b; Wallberg et al, 2010). Goethals et al (Goethals et al, 2000) labeled 55 Co to ethylene diamine tetraacetic acid (EDTA) and characterized this complex for the application in the measurement of the glomerular filtration rate in kidneys via PET, a study which is commonly performed with the perfusion tracer 51 Cr-EDTA (Chantler et al, 1969).…”

“…Goethals et al (Goethals et al, 2000) labeled 55 Co to ethylene diamine tetraacetic acid (EDTA) and characterized this complex for the application in the measurement of the glomerular filtration rate in kidneys via PET, a study which is commonly performed with the perfusion tracer 51 Cr-EDTA (Chantler et al, 1969). Srivastava et al (1994), Thisgaard et al (2011b) and Mastren et al (2015) successfully labeled 55 Co to bifunctional chelators (BFC) conjugated to targeting peptides or proteins, although with very low effective specific activities (ESA): 3.7, 0.21, and 2.0 GBq/μmol, respectively. Dam et al (2016), has reported the highest ESA of 55 Co at 30 GBq/μmol by labeling a NOTA-conjugated bombesin analog under microwave heating in order to accelerate the labeling reaction.…”

“…Of the three publications in which isotopically enriched 54 Fe targets were bombarded with deuteron beams (Sharma et al, 1986; Thisgaard et al, 2011b; Zaman et al, 2003), only the one by Zaman et al clearly reports a numerical value of the recycling efficiency of the expensive target material of 80% and the maximum current employed is merely 18 μA by Thisgaard et al…”