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Preclinical 89Zr Immuno-PET of high-grade serous ovarian cancer and lymph node metastasis

Lookup NU author(s): Dr James Knight

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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.


Publication metadata

Author(s): Sharma SK, Sevak KK, Monette S, Carlin SD, Knight JC, Wuest FR, Sala E, Zeglis BM, Lewis JS

Publication type: Article

Publication status: Published

Journal: Journal of Nuclear Medicine

Year: 2016

Volume: 57

Issue: 5

Pages: 771-776

Print publication date: 01/05/2016

Online publication date: 02/02/2016

Acceptance date: 07/01/2016

ISSN (print): 0161-5505

ISSN (electronic): 2159-662X

Publisher: Society of Nuclear Medicine Inc.

URL: https://doi.org/10.2967/jnumed.115.167072

DOI: 10.2967/jnumed.115.167072

PubMed id: 26837339


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