Abstract
Mesothelin is a tumor differentiation antigen expressed by epithelial tumors, including pancreatic cancer. Currently, mesothelin is being targeted with an antibodydrug conjugate (ADC) consisting of a mesothelin-specific antibody coupled to a highly potent chemotherapeutic drug. Considering the toxicity of the ADC and reduced accessibility of pancreatic tumors, non-invasive imaging could provide necessary information. We therefore developed a zirconium-89 (Zr-89) labeled anti-mesothelin antibody (Zr-89-AMA) to study its biodistribution in human pancreatic tumor bearing mice. Biodistribution and dose-finding of Zr-89-AMA were studied 144 h after tracer injection in mice with subcutaneously xenografted HPAC. MicroPET imaging was performed 24, 72 and 144 h after tracer injection in mice bearing HPAC or Capan-2. Tumor uptake and organ distribution of Zr-89-AMA were compared with nonspecific 111In-IgG. Biodistribution analyses revealed a dose-dependent Zr-89-AMA tumor uptake. Tumor uptake of Zr-89-AMA was higher than 111In-IgG using the lowest tracer dose. MicroPET showed increased tumor uptake over 6 days, whereas activity in blood pool and other tissues decreased. Immunohistochemistry showed that mesothelin was expressed by the HPAC and CAPAN-2 tumors and fluorescence microscopy revealed that AMA-800CW was present in tumor cell cytoplasm. Zr-89-AMA tumor uptake is antigen-specific in mesothelin-expressing tumors. Zr-89-AMA PET provides non-invasive, real-time information about AMA distribution and tumor targeting.
Original language | English |
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Pages (from-to) | 42081-42090 |
Number of pages | 10 |
Journal | Oncotarget |
Volume | 6 |
Issue number | 39 |
DOIs | |
Publication status | Published - 8-Dec-2015 |
Keywords
- mesothelin
- pancreatic cancer
- zirconium-89
- PET imaging
- IRDye 800CW
- GROWTH-FACTOR
- CANCER
- PET
- ZR-89-TRASTUZUMAB
- BIODISTRIBUTION
- EXPRESSION
- THERAPY
- MODELS