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

The most commonly used radiometal for dosimetry in radio immunotherapy is In-111. This radionuclide has suitable physical properties and its chelation chemistry is similar to that of Y-90, which is frequently used in radiotherapy. Since imaging with a gamma-ray emitting radionuclide is less accurate than PET-imaging, we evaluated the labelling of a monoclonal antibody with the beta(+)-emitter Ga-68 and the in vitro stability of the labelled antibody in human serum. We focused our studies on the bifunctional chelators BnDTPA, CHX-A-DTPA, and mx-DTPA conjugated to the anti-CD45 monoclonal antibody YAML568. The incorporation of Ga-68 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 [Ga-68]Bn-DTPA. After 3 h at 37 degrees C in human serum 66% of Ga-68 is transchelated from the antibody to transferrin. The [Ga-68]CHX-A-DTPA chelate is kinetically more stable. 83% of Ga-68 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 [Ga-68]mx-DTPA-conjugate enable the accurate determination of antibody biodistribution for dosimetry using PET in combination with conventional [In-111]anti-CD45 scintigraphy.