Fully Automated Production and Characterization of ⁶⁴Cu and Proof‐of‐Principle Small‐Animal PET Imaging Using ⁶⁴Cu‐Labelled CA XII Targeting 6A10 Fab

Abstract

Cu is a cyclotron-produced radionuclide which offers, thanks to its characteristic decay scheme, the possibility of combining positron emission tomography (PET) investigations with radiotherapy. We evaluated the Alceo system from Comecer SpA to automatically produce Cu for radiolabelling purposes. We established a Cu production routine with high yields and radionuclide purity in combination with excellent operator radiation protection. The carbonic anhydrase XII targeting 6A10 antibody Fab fragment was successfully radiolabelled with the produced Cu, and proof-of-principle small-animal PET experiments on mice bearing glioma xenografts were performed. We obtained a high tumor-to-contralateral muscle ratio, which encourages further in vivo investigations of the radioconjugate regarding a possible application in diagnostic tumor imaging.

Inhibitory Monoclonal Antibodies and Their Recombinant Derivatives Targeting Surface-Exposed Carbonic Anhydrase XII on Cancer Cells

“…Moreover, it inhibited the catalytic activity of CA XII and the growth of tumor cells not only in vitro but also in vivo xenograft models [28]. Recently, a 6A10-derived Fab fragment developed in CHO cells was labeled with 177 Lu or 64 Cu and tested both in vitro and in vivo for PET or RIT applications [30,31]. Furthermore, a humanized antibody 4AG4 targeting CA XII was generated and showed blocking of CA XII enzymatic activity [50].…”

“…As CA XII might contribute to drug-resistant cancer phenotype [64], there is a growing demand for new reliable tools for CA XII detection. Cancer therapy based on CA XII targeting is also a promising trend, thus new formats of molecules interacting with CA XII contribute to the progress in this field [30,31,50]. From the MAb collection, we have selected the MAb 14D6 with desired features and generated its recombinant derivatives scFv and scFv-Fc that maintained the specificity of the parental MAb.…”

“…The Fab fragment of this antibody was labeled with 177 Lu or 64 Cu to be used as an agent for radioimmunotherapy (RIT) or positron emission tomography (PET). It showed specific binding to CA XII on tumor cells in mice xenografts [30,31].…”

Electrochemical deposition of nickel targets from aqueous electrolytes for medical radioisotope production in accelerators: a review

“…The overall procedure of the production of the medical radioisotopes involves several steps, including the target preparation, irradiation of the target in an accelerator, separation of the reaction products and recovery of non-reacted target isotopes from the target material and purification of such obtained isotopes [12,13,17,31,33,34,46,[52][53][54]80]. This paper focuses on the first stage of the procedure, i.e.…”

“…Other than the latter disadvantages of the electrochemical deposition include possibility of contamination of the target with impurities from the electrolyte bath which are co-deposited or coprecipitated with the deposited metal [74]. Further on, the electrochemically plated deposits may have non-uniform thickness [31,46,74] and when the deposition is carried out from a solution with low metal content, the process can be time consuming (e.g. [2,8,10,13,17,19,45,48,[59][60][61][62][63][64][65][66]).…”