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JOURNAL ARTICLE

Noninvasive Trafficking of Brentuximab Vedotin and PET Imaging of CD30 in Lung Cancer Murine Models

Lei Kang, Dawei Jiang, Emily B Ehlerding, Todd E Barnhart, Dalong Ni, Jonathan W Engle, Rongfu Wang, Peng Huang, Xiaojie Xu, Weibo Cai
Molecular Pharmaceutics 2018 April 2, 15 (4): 1627-1634
29537283
CD30 has been considered a unique diagnostic and therapeutic target for CD30-positive lymphomas and some lung diseases. Additionally, CD30 has shown high expression in clinical lung cancer samples. In this study, 89 Zr-radiolabeled brentuximab vedotin (BV) was developed for in vivo tracking of BV and imaging CD30 expression in lung cancer models via conjugation with desferrioxamine (Df). CD30 expression in three lung cancer cell lines (H460, H358, and A549) was quantified by Western blot. Flow cytometry and saturation binding assays were used to evaluate the binding capabilities of the tracer in vitro. After longitudinal positron emission tomography (PET) imaging and quantitative analysis were performed, ex vivo biodistribution and histological studies were used to verify PET results. Finally, dosimetric extrapolation of murine data to humans was performed. At the cellular level, CD30 was found to be expressed on H460 and A549 cells with the highest and lowest levels of expression, respectively. Both Df-BV and 89 Zr-Df-BV displayed high binding affinity to H460 cells. PET images and their quantification verified that BV accumulated in H460 tumor models (9.93 ± 2.70% ID/g at 24 h after injection; n = 4) at the highest level, followed by H358 and A549 tumors (8.05 ± 2.43 and 5.00 ± 1.56% ID/g; n = 4). The nonspecific 89 Zr-labeled IgG showed a low tumor uptake of 5.2 ± 1.0% ID/g for H460 models. Ex vivo biodistribution and fluorescence immunohistochemistry also corroborated these findings. Dosimetric results displayed safe dose estimations. Therefore, 89 Zr-Df-BV provides a potential agent for evaluating CD30 expression noninvasively in lung cancer, and also for imaging of brentuximab vedotin for better understanding of its pharmacokinetics.

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