PMID- 29537283 OWN - NLM STAT- MEDLINE DCOM- 20190315 LR - 20191210 IS - 1543-8392 (Electronic) IS - 1543-8384 (Print) IS - 1543-8384 (Linking) VI - 15 IP - 4 DP - 2018 Apr 2 TI - Noninvasive Trafficking of Brentuximab Vedotin and PET Imaging of CD30 in Lung Cancer Murine Models. PG - 1627-1634 LID - 10.1021/acs.molpharmaceut.7b01168 [doi] AB - 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. FAU - Kang, Lei AU - Kang L AD - Department of Nuclear Medicine , Peking University First Hospital , Beijing 100034 , China. AD - Department of Radiology , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States. FAU - Jiang, Dawei AU - Jiang D AUID- ORCID: 0000-0002-4072-0075 AD - Department of Radiology , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States. AD - Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Laboratory of Evolutionary Theranostics, School of Biomedical Engineering, Health Science Center , Shenzhen University , Shenzhen 518060 , China. FAU - Ehlerding, Emily B AU - Ehlerding EB AD - Department of Medical Physics , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States. FAU - Barnhart, Todd E AU - Barnhart TE AD - Department of Medical Physics , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States. FAU - Ni, Dalong AU - Ni D AUID- ORCID: 0000-0001-6679-5414 AD - Department of Radiology , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States. FAU - Engle, Jonathan W AU - Engle JW AD - Department of Medical Physics , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States. FAU - Wang, Rongfu AU - Wang R AD - Department of Nuclear Medicine , Peking University First Hospital , Beijing 100034 , China. FAU - Huang, Peng AU - Huang P AUID- ORCID: 0000-0003-3651-7813 AD - Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Laboratory of Evolutionary Theranostics, School of Biomedical Engineering, Health Science Center , Shenzhen University , Shenzhen 518060 , China. FAU - Xu, Xiaojie AU - Xu X AD - Department of Medical Molecular Biology , Beijing Institute of Biotechnology , Beijing 100850 , China. FAU - Cai, Weibo AU - Cai W AUID- ORCID: 0000-0003-4641-0833 AD - Department of Radiology , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States. AD - Department of Medical Physics , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States. AD - University of Wisconsin Carbone Cancer Center , Madison , Wisconsin 53705 , United States. LA - eng GR - P30 CA014520/CA/NCI NIH HHS/United States GR - T32 CA009206/CA/NCI NIH HHS/United States GR - T32 GM008505/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180320 PL - United States TA - Mol Pharm JT - Molecular pharmaceutics JID - 101197791 RN - 0 (Immunoconjugates) RN - 0 (Ki-1 Antigen) RN - 0 (Radioisotopes) RN - 7XL5ISS668 (Brentuximab Vedotin) RN - C6V6S92N3C (Zirconium) RN - J06Y7MXW4D (Deferoxamine) RN - NTM296JU95 (Zirconium-89) SB - IM MH - A549 Cells MH - Animals MH - Brentuximab Vedotin MH - Cell Line, Tumor MH - Deferoxamine/metabolism MH - Disease Models, Animal MH - Female MH - Humans MH - Immunoconjugates/*metabolism MH - Ki-1 Antigen/*metabolism MH - Lung Neoplasms/*metabolism MH - Lymphoma/metabolism MH - Mice MH - Mice, Nude MH - Positron-Emission Tomography/methods MH - Radioisotopes/metabolism MH - Tissue Distribution/physiology MH - Zirconium/metabolism PMC - PMC5920523 MID - NIHMS956723 OTO - NOTNLM OT - CD30 OT - Zr-89 OT - brentuximab vedotin OT - lung cancer OT - positron emission tomography (PET) COIS- Notes The authors declare no competing financial interest. EDAT- 2018/03/15 06:00 MHDA- 2019/03/16 06:00 PMCR- 2019/04/02 CRDT- 2018/03/15 06:00 PHST- 2018/03/15 06:00 [pubmed] PHST- 2019/03/16 06:00 [medline] PHST- 2018/03/15 06:00 [entrez] PHST- 2019/04/02 00:00 [pmc-release] AID - 10.1021/acs.molpharmaceut.7b01168 [doi] PST - ppublish SO - Mol Pharm. 2018 Apr 2;15(4):1627-1634. doi: 10.1021/acs.molpharmaceut.7b01168. Epub 2018 Mar 20.