Page 83 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Initial clinical trials with 89Zr-immuno-PET in oncology
samples 2 and 3 hours post injection of the scouting dose revealed that only <10 %
of the injected dose of 89Zr-cetuximab was left in the blood circulation. When subsequently cold cetuximab (500 mg/m2) was administered, 89Zr-cetuximab
reappeared in the blood, indicating that it can be reversibly extracted, most
probably by the liver. On the other hand, the biological half-life of 89Zr-cetuximab,
if administered directly after the unlabeled dose, was comparable with the half-life
as reported for unlabeled cetuximab. This indicates that upon such sequential administration 89Zr-cetuximab indeed reflects the biodistribution of unlabeled
cetuximab. Future studies are required to assess to which extent sequential administration of imaging and therapeutic doses influences tumor biodistribution 4 and tumor uptake of 89Zr-cetuximab.
89Zr-labeled anti-PSMA in prostate cancer
Current clinical challenges in imaging of metastatic prostate cancer include limited sensitivity and specificity to detect early metastases (especially in bone) and active disease and to monitor treatment of metastatic prostate cancer. The humanized mAb huJ591 targets the extracellular domain of prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein expressed by both benign and malignant prostate epithelial cells. Nearly all prostate cancers express PSMA. Upon binding, the huJ591-PSMA complex becomes rapidly internalized. Binding of anti-PSMA mAbs to non-prostate tissue, as the liver, duodenal epithelial (brush border) cells and proximal tubule cells in the kidney, has been observed, as well as binding to tumor-associated neovasculature in other solid malignancies, including clear cell renal carcinoma, colon and breast carcinoma (37).
Recently, Pandit-Taskar et al. performed a clinical study with 89Zr-labeled huJ591 in 50 patients with castrate-resistant metastatic prostate cancer (38). Results of the first 10 patients were reported separately, including assessment of optimal imaging time post-injection for lesion detection of 89Zr-huJ591 PET imaging (39). These 10 patients received 4 scans within 8 days after injection. Based on optimal tumor-to-background ratios, the other 40 patients were imaged once at 6-8 days p.i.. This relatively long period post injection required for optimal imaging, may be a practical limitation of 89Zr-immuno-PET for routine application in diagnosis. Promising alternative ligands for molecular imaging of prostate cancer are smaller molecules as radiolabeled minibodies or urea-based small peptides, although none have been validated in controlled clinical trials for routine clinical use (40).
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