Long-Lived Positron Emitters Zirconium-89 and Iodine-124 for Scouting of Therapeutic Radioimmunoconjugates with PET

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Abstract
Antibody-PET imaging might be of value for the selection of radioimmunotherapy (RIT) candidates to confirm tumor targeting and to estimate radiation doses to tumor and normal tissues. One of the requirements to be set for such a scouting procedure is that the biodistributions of the diagnostic and therapeutic radioimmunoconjugates should be similar. In the present study we evaluated the potential of the positron emitters zirconium-89 (89Zr) and iodine-124 (124I) for this approach, as these radionuclides have a relatively long half-life that matches with the kinetics of MAbs in vivo (t1/2 3.27 and 4.18 days, respectively). After radiolabeling of the head and neck squamous cell carcinoma (HNSCC)-selective chimeric antibody (cMAb) U36, the biodistribution of two diagnostic (cMAb U36-N-sucDf-89Zr and cMAb U36-124I) and three therapeutic radioimmunoconjugates (cMAb U36-p-SCN-Bz-DOTA-88Y-with 88Y being substitute for 90Y, cMAb U36-131I, and cMAb U36-MAG3-186Re) was assessed in mice with HNSCC-xenografts, at 24, 48, and 72 hours after injection. Two patterns of biodistribution were observed, one pattern matching for 89Zr- and 88Y-labeled cMAb U36 and one pattern matching for 124I-, 131I-, and 186Re-cMAb U36. The most remarkable differences between both patterns were observed for uptake in tumor and liver. Tumor uptake levels were 23.2 ± 0.5 and 24.1 ± 0.7%ID/g for the 89Zr- and 88Y-cMAb U36 and 16.0 ± 0.8, 15.7 ± 0.79 and 17.1 ± 1.6%ID/g for 124I-, 131I-, and 186Re-cMAb U36-conjugates, respectively, at 72 hours after injection. For liver these values were 6.9 ± 0.8 (89Zr), 6.2 ± 0.8 (88Y), 1.7 ± 0.1 (124I), 1.6 ± 0.1 (131I), and 2.3 ± 0.1 (186Re), respectively. These preliminary data justify the further development of antibody-PET with 89Zr-labeled MAbs for scouting of therapeutic doses of 90Y-labeled MAbs. In such approach 124I-labeled MAbs are most suitable for scouting of 131I- and 186Re-labeled MAbs.

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