Preclinical 89Zr Immuno-PET of High-Grade Serous Ovarian Cancer and Lymph Node Metastasis
| Autor: | Evis Sala, Kuntal K. Sevak, Jason S. Lewis, Frank Wuest, Sebastien Monette, James C. Knight, Brian M. Zeglis, Sean Carlin, Sai Kiran Sharma |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Biodistribution
Pathology medicine.medical_specialty Immunoconjugates endocrine system diseases Radioimmunoconjugate Article 030218 nuclear medicine & medical imaging 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor medicine Animals Humans Radiology Nuclear Medicine and imaging Tissue Distribution Ovarian Neoplasms Radioisotopes medicine.diagnostic_test business.industry Antibodies Monoclonal Membrane Proteins medicine.disease female genital diseases and pregnancy complications Cell Transformation Neoplastic Positron emission tomography 030220 oncology & carcinogenesis CA-125 Antigen Lymphatic Metastasis Positron-Emission Tomography Immunohistochemistry Histopathology Female Lymph Zirconium Ovarian cancer business Ex vivo |
| Zdroj: | Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 57(5) |
| ISSN: | 1535-5667 |
| Popis: | The elevation of cancer antigen 125 (CA125) levels in the serum of asymptomatic patients precedes the radiologic detection of high-grade serous ovarian cancer by at least 2 mo and the final clinical diagnosis by 5 mo. PET imaging of CA125 expression by ovarian cancer cells may enhance the evaluation of the extent of disease and provide a roadmap to surgery as well as detect recurrence and metastases. Methods:89Zr-labeled mAb-B43.13 was synthesized to target CA125 and evaluated via PET imaging and biodistribution studies in mice bearing OVCAR3 human ovarian adenocarcinoma xenografts. Ex vivo analysis of tumors and lymph nodes was performed via autoradiography, histopathology, and immunohistochemistry. Results: PET imaging using 89Zr-DFO-mAb-B43.13 (DFO is desferrioxamine) clearly delineated CA125-positive OVCAR3 xenografts as early as 24 h after the administration of the radioimmunoconjugate. Biodistribution studies revealed accretion of 89Zr-DFO-mAb-B43.13 in the OVCAR3 tumors, ultimately reaching 22.3 ± 6.3 percentage injected dose per gram (%ID/g) at 72 h after injection. Most interestingly, activity concentrations greater than 50 %ID/g were observed in the ipsilateral lymph nodes of the xenograft-bearing mice. Histopathologic analysis of the immuno-PET–positive lymph nodes revealed the presence of grossly metastasized ovarian cancer cells within the lymphoid tissues. In control experiments, only low-level, non-specific uptake of 89Zr-labeled isotype IgG was observed in OVCAR3 tumors; similarly, low-activity concentrations of 89Zr-DFO-mAb-B43.13 accumulated in CA125-negative SKOV3 tumors. Conclusion: Immuno-PET with 89Zr-labeled mAb-B43.13 is a potential strategy for the noninvasive delineation of extent of disease and may add value in treatment planning and treatment monitoring of high-grade serous ovarian cancer. |
| Databáze: | OpenAIRE |
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