Page 84 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 4
Pandit-Taskar et al. evaluated performance characteristics of 89Zr-DFO- huJ591 PET/CT for detecting metastases compared to conventional imaging modalities (baseline FDG-PET, 99mTc-methylenediphosphonate (MDP) bone scans and CT scans) and pathology, to provide evidence for the use of 89Zr-huJ591 as an imaging biomarker. In a lesion-based analysis 89Zr-J591 imaging demonstrated superior visualisation of bone lesions relative to conventional imaging, see Figure 3. However, detection of soft tissue lesions was suboptimal. A generalized lower tumor uptake was observed for soft tissue lesions compared to bone lesions. Low uptake was observed in normal bone and considered to be non-specific. Among the possibilities explaining a lower tumor uptake in soft tissue are: lower PSMA expression, absence of tumor in lesions presumed to be disease by CT and FDG- PET scan, or impaired accessibility of PSMA for intact mAbs. For the biopsy- confirmed lesions overall accuracy of 89Zr-J591 was 95.2% (20/21) for osseous lesions and 60% (15/25) for soft-tissue lesions. No data is provided on 89Zr-J591 uptake related to PSMA expression in tumor biopsies.
The authors conclude that 89Zr-huJ591 imaging is able to detect active disease earlier than conventional imaging, making PSMA an attractive target for diagnosis of prostate cancer. Despite the fact that just a small proportion of lesions were biopsied, statistical arguments indicated that 89Zr-huJ591 imaging detects 50% more bone lesions (occult disease) than bone scan. However, no single imaging modality can serve as gold standard, therefore a known site of disease was defined as any lesions identified by conventional imaging at baseline. Small lesions were most probably missed, while the treatment of patients after imaging was variable, which limits the detection of lesions through follow-up imaging.
In this 89Zr-immuno-PET study a total mAb dose of 25 mg huJ591 was used, of which 1.7 mg was 89Zr-labeled (203 MBq). This dose was based on prior studies with 111In-J591 and 177Lu-J591 that showed saturation of PSMA expressed by the normal liver at 25 mg of huJ591 (41). A dose-dependent uptake in the liver with increasing mAb dose was observed, and optimal trade off was reached at a mAb dose of 25 mg. The unlabeled dose of huJ591 was administered intravenously within 5 minutes, immediately followed by injection of 89Zr-huJ591 within 1 minute.
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