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The most commonly used radiometal for dosimetry in radioimmunotherapy is  111 In. This radionuclide has suitable physical properties and its chelation chemistry is similar to that of  90 Y, 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  68 Ga 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  68 Ga into the antibody is rapid for all three ligands. After 5 minutes the radiochemical yield is &gt; 95%. The serum stability differs strongly depending on the chelator. The least stable chelate is [ 68 Ga]Bn-DTPA. After 3 h at 37°C in human serum 66% of  68 Ga is transchelated from the antibody to transferrin. The [ 68 Ga]CHX-A ′′ -DTPA chelate is kinetically more stable. 83% of  68 Ga 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 [ 68 Ga] mx -DTPA-conjugate enable the accurate determination of antibody biodistribution for dosimetry using PET in combination with conventional [ 111 In]anti-CD45 scintigraphy.

radiochimica acta

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