title: 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 ((89)Zr) and iodine-124 ((124)I) 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-(89)Zr and cMAb U36-(124)I) and three therapeutic radioimmunoconjugates (cMAb U36-p-SCN-Bz-DOTA-(88)Y-with (88)Y being substitute for (90)Y, cMAb U36-(131)I, and cMAb U36-MAG3-(186)Re) 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 (89)Zr- and (88)Y-labeled cMAb U36 and one pattern matching for (124)I-, (131)I-, and (186)Re-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 (89)Zr- and (88)Y-cMAb U36 and 16.0 +/- 0.8, 15.7 +/- 0.79 and 17.1 +/- 1.6%ID/g for (124)I-, (131)I-, and (186)Re-cMAb U36-conjugates, respectively, at 72 hours after injection. For liver these values were 6.9 +/- 0.8 ((89)Zr), 6.2 +/- 0.8 ((88)Y), 1.7 +/- 0.1 ((124)I), 1.6 +/- 0.1 ((131)I), and 2.3 +/- 0.1 ((186)Re), respectively. These preliminary data justify the further development of antibody-PET with (89)Zr-labeled MAbs for scouting of therapeutic doses of (90)Y-labeled MAbs. In such approach (124)I-labeled MAbs are most suitable for scouting of (131)I- and (186)Re-labeled MAbs.
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy; D045744:Cell Line, Tumor; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D018796:Immunoconjugates / Q000737:chemistry / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D011868:Radioisotopes; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D012211:Rhenium; D013997:Time Factors; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes; D015040:Zirconium
chemical_list: D000911:Antibodies, Monoclonal; C112697:CD44v6 antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D011868:Radioisotopes; D011993:Recombinant Fusion Proteins; D015021:Yttrium Radioisotopes; D012211:Rhenium; D015040:Zirconium