Immune-PET of human colon xenograft-bearing BALB/c nude mice using I-124-CDR-grafted humanized A33 monoclonal antibody

Radiolabeling monoclonal antibodies (mAbs) allows the evaluation of biodist ribution of constructs in vivo through gamma camera imaging and also permit s quantitation of mAb uptake in tumors through biopsy-based counting techni ques. The quantitation of radiolabeled mAb uptake in cancer patients is com plicated by the attenuation of gamma emissions of routinely used isotopes ( e.g., I-131 and In-111) and the spatial resolution and sensitivity of gamma cameras. Methods: We used the positron-emitting isotope I-124 (half-life [ T-1/2] = 4.2 d) to label the recombinant humanized anti-colorectal cancer A 33 antibody (huA33) and evaluated its biodistribution properties and PET im aging characteristics in BALB/c nude mice bearing SW1222 colorectal xenogra fts and control colon tumors. Results: The immunoreactivity of radioconjuga te was 78% as determined using the cell-binding Lindmo assay. The apparent association constant was found to be 2.2 x 10(9) M-1, and the number of ant ibody binding sites per cell was 371,000. The radioconjugate was found to b e stable in serum obtained from mice at various times after injection. Assu ming a two-compartment model with a four-parameter fit of mean blood levels , the T(1/2)alpha was 1.5 h and the T(1/2)beta was 38.2 h. Excellent tumor uptake was obtained, with maximal uptake reaching 50.0 +/- 7.0 percentage i njected dose per gram of tumor by 4 d after injection. Specificity of local ization was shown by lack of uptake in control tumor. PET imaging detected antigen-positive tumor by 4 h after injection, and high-resolution images w ere obtained by 24 h after injection. Conclusion: In clinical trials using PET, huA33 labeled with I-124 has potential for imaging and staging colon t umors and quantifying antibody uptake in colon tumors in vivo.