Labelling of a monoclonal antibody with ⁶⁸Ga using three DTPA-based bifunctional ligands and their in vitro evaluation for application in radioimmunotherapy

The most commonly used radiometal for dosimetry in radioimmunotherapy is ¹¹¹In. This radionuclide has suitable physical properties and its chelation chemistry is similar to that of ⁹⁰Y, which is frequently used in radiotherapy. Since imaging with a γ-ray emitting radionuclide is less accurate than PET-imaging, we evaluated the labelling of a monoclonal antibody with the β⁺-emitter ⁶⁸Ga and the in vitro stability of the labelled antibody in human serum. We focused our studies on the bifunctional chelators Bn-DTPA, CHX-A^′′-DTPA, and mx-DTPA conjugated to the anti-CD45 monoclonal antibody YAML568. The incorporation of ⁶⁸Ga into the antibody is rapid for all three ligands. After 5 minutes the radiochemical yield is > 95%. The serum stability differs strongly depending on the chelator. The least stable chelate is [⁶⁸Ga]Bn-DTPA. After 3 h at 37°C in human serum 66% of ⁶⁸Ga is transchelated from the antibody to transferrin. The [⁶⁸Ga]CHX-A^′′-DTPA chelate is kinetically more stable. 83% of ⁶⁸Ga were still chelated to the antibody after 4h in human serum. The best results were obtained using mx-DTPA. Only 5% were transchelated from the labelled antibody to transferrin after 4h in human serum. The high in vitro stability and the low transchelation tendency of the [⁶⁸Ga]mx-DTPA-conjugate enable the accurate determination of antibody biodistribution for dosimetry using PET in combination with conventional [¹¹¹In]anti-CD45 scintigraphy.