Page 85 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Initial clinical trials with 89Zr-immuno-PET in oncology
Figure 3. 89Zr-huJ591-PET and conventional imaging modalities of a patient with rising prostate specific 4 antigen. 99mTc-MDP bone scan shows only a few lesions. FDG-PET shows nodal disease in the thorax, retroperitoneum, and pelvic region and a few bone lesions in the spine. Overall more bone lesions were seen
on 89Zr-huJ591-PET than on FDG-PET, including multiple lesions in vertebrae, pelvic bones, ribs and
humerus. Targeting was also seen to the retroperitoneal and pelvic lymph nodes by 89Zr-huJ59-PET.
(A) Anterior and posterior 99mTc-MDP bone scan (B) FDG-PET maximum intensity projection (C) 89Zr-huJ591 PET
(D) FDG-PET sagittal fused image
(E) 89Zr-hu J591 PET sagittal fused image
Reprinted with permission from “Pandit-Taskar, N., O’Donoghue, J.A., Beylergil, V., Lyashchenko, S., Ruan, S., Solomon, S.B., et al. (2014) 89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer. Eur. J. Nucl. Med. Mol. Imaging. 41, 2093-2105. doi: 10.1007/s00259-014-2830-7”
89Zr-labeled anti-MSLN in pancreatic and ovarian carcinoma
For several tumor types, such as pancreatic and ovarian carcinoma, no important drug targets are available yet for targeted therapy. A promising approach is the exploitation of tumor-specific membrane proteins, even those without a known role in oncogenesis, as targets for delivery of potent drugs by ADCs. In this respect, a potential target molecule, with largely unknown biological function, is membrane-bound surface glycoprotein mesothelin (MSLN). It is minimally expressed by normal mesothelial cells, lining pleural, pericardial and peritoneal surfaces. Besides in mesothelioma, it is also highly overexpressed in 80-100% of pancreatic and ovarian cancers (and some other cancers). In preclinical studies with MSLN-expressing tumor bearing mice, 89Zr-anti-MSLN antibody MMOT0530A showed progressive and antigen-specific tumor uptake with micro- PET (42).
Therefore, Lamberts et al. evaluated 89Zr-labeled MMOT0530A as a predictive imaging biomarker for treatment (in a phase I setting) with the ADC
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