Preclinical (89)Zr immuno-PET of high-grade serous ovarian cancer and lymph node metastasis Journal Article

Authors: Sharma, S. K.; Sevak, K. K.; Monette, S.; Carlin, S. D.; Knight, J. C.; Wuest, F. R.; Sala, E.; Zeglis, B. M.; Lewis, J. S.
Article Title: Preclinical (89)Zr immuno-PET of high-grade serous ovarian cancer and lymph node metastasis
Abstract: The elevation of cancer antigen 125 (CA125) levels in the serum of asymptomatic patients precedes the radiologic detection of highgrade 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-DFOmAb- 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-bearingmice. 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-DFOmAb- 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 highgrade serous ovarian cancer. 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
Keywords: positron emission tomography; ovarian cancer; ca125; 89zr
Journal Title: Journal of Nuclear Medicine
Volume: 57
Issue: 5
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2016-05-01
Start Page: 771
End Page: 776
Language: English
DOI: 10.2967/jnumed.115.167072
PROVIDER: scopus
PUBMED: 26837339
PMCID: PMC4959443
Notes: Article -- Export Date: 2 June 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Evis Sala
    110 Sala
  2. Sebastien Monette
    98 Monette
  3. Jason S Lewis
    354 Lewis
  4. Sean Denis Carlin
    83 Carlin
  5. Kuntalkumar Sevak
    11 Sevak
  6. Sai Kiran   Sharma
    22 Sharma