RT Journal Article
SR Electronic
T1 In vivo visualization of brentuximab vedotin and immunoPET of CD30 in lung cancer murine models
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 171
OP 171
VO 59
IS supplement 1
A1 Lei Kang
A1 Dawei Jiang
A1 Emily Ehlerding
A1 Dalong NI
A1 Bo Yu
A1 Todd Barnhart
A1 Rongfu Wang
A1 Weibo Cai
YR 2018
UL http://jnm.snmjournals.org/content/59/supplement_1/171.abstract
AB 171Objectives: CD30 has been considered a unique diagnostic and therapeutic target for several lymphomas. It also shows high expression in clinical lung cancer samples. Brentuximab vedotin (BV) is one of most successful anti-CD30 antibody-drug conjugates (ADCs) for the treatment of relapsed lymphomas. Therefore, the trafficking of this ADC and monitoring its therapeutic effect in vivo is important for understanding the effects of lymphoma treatment. In this study, we radiolabeled BV with 89Zr for tracking BV and imaging CD30 expression noninvasively in three lung cancer models. Methods: BV was radiolabeled with 89Zr (t1/2 = 78.4 h) via conjugation with desferrioxamine (Df). CD30 expression in three lung cancer cell lines (H460, H358, and A549) was measured and quantified by Western blot. Flow cytometry was used to display the binding ability of conjugated BV with CD30 in vitro. Next, the uptake of 89Zr-Df-BV was evaluated by longitudinal PET imaging up to 120 h after injection in H460, H358, and A549 tumor bearing mice. 89Zr-Df-IgG was also evaluated for the non-specific control group in the CD30-positive tumor model. Ex vivo biodistribution and histological studies were used to verify PET results. Finally, dosimetric extrapolation of murine data to humans was performed. Results: By in vitro analysis, CD30 was found to be expressed on all three lung cell lines with H460 and A549 showing the highest and lowest level of expression, respectively. Df-BV or BV displayed high binding affinity to H460 cells by flow cytometry. PET imaging and quantification verified these findings as the tracer accumulated highest in the H460 tumor model (9.93 ± 2.70 %ID/g at 24 h after injection; n = 4), followed by H358 and A549 tumors with uptakes of 8.05 ± 2.43 %ID/g and 5.00 ± 1.56 %ID/g at 24 h, respectively (n = 4). 89Zr radiolabeled non-specific IgG showed a low tumor uptake of 5.2 ± 1.0 %ID/g for H460 model. Ex vivo biodistribution corroborated the PET imaging findings. Fluorescence Immunohistochemistry of tumor tissues also supported the different expression of CD30 in three kinds of lung cancer tumors. Dosimetric results displayed safe dose estimations for potential human usage. Conclusions: 89Zr-Df-brentuximab vedotin 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.