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

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(t_1/2 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.