PMID- 29450576
OWN - NLM
STAT- MEDLINE
DCOM- 20181217
LR  - 20190701
IS  - 1619-7089 (Electronic)
IS  - 1619-7070 (Print)
IS  - 1619-7070 (Linking)
VI  - 45
IP  - 8
DP  - 2018 Jul
TI  - ImmunoPET imaging of CD38 in murine lymphoma models using (89)Zr-labeled 
      daratumumab.
PG  - 1372-1381
LID - 10.1007/s00259-018-3941-3 [doi]
AB  - PURPOSE: CD38 is considered a potential biomarker for multiple myeloma (MM) and 
      has shown a strong link with chronic lymphocytic leukemia due to high and uniform 
      expression on plasma cells. In vivo evaluation of CD38 expression may provide 
      useful information about lesion detection and prognosis of treatment in MM. In 
      this study, immunoPET imaging with (89)Zr-labeled daratumumab was used for 
      differentiation of CD38 expression in murine lymphoma models to provide a 
      potential non-invasive method for monitoring CD38 in the clinic. METHODS: 
      Daratumumab was radiolabeled with (89)Zr (t(1/2) = 78.4 h) via conjugation with 
      desferrioxamine (Df). After Western blot (WB) was used to screen CD38 expression 
      in five lymphoma cell lines, flow cytometry and cellular binding assays were 
      performed to test the binding ability of labeled or conjugated daratumumab with 
      CD38 in vitro. PET imaging and biodistribution studies were performed to evaluate 
      CD38 expression after injection of (89)Zr-Df-daratumumab. (89)Zr-Df-IgG was also 
      evaluated as a non-specific control group in the Ramos model. Finally, CD38 
      expression in tumor tissues was verified by histological analysis. RESULTS: Using 
      WB screening, the Ramos cell line was found to express the highest level of CD38 
      while the HBL-1 cell line had the lowest expression. Df-conjugated and 
      (89)Zr-labeled daratumumab displayed similar high binding affinities with Ramos 
      cells. PET imaging of (89)Zr-Df-daratumumab showed a high tumor uptake of up to 
      26.6 +/- 8.0 %ID/g for Ramos at 120 h post-injection, and only up to 6.6 +/- 2.9 
      %ID/g for HBL-1 (n = 4). Additionally, (89)Zr-Df-IgG demonstrated a low tumor 
      uptake in the Ramos model (only 4.3 +/- 0.8 %ID/g at 120 h post-injection). Ex vivo 
      biodistribution studies showed similar trends with imaging results. 
      Immunofluorescence staining of tumor tissues verified higher CD38 expression of 
      Ramos than that of HBL-1. CONCLUSIONS: The role of (89)Zr-Df-daratumumab was 
      investigated for evaluating CD38 expression in lymphoma models non-invasively and 
      was found to be to a promising imaging agent of CD38-positive hematological 
      diseases such as MM in future clinical applications.
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, WI, 53705, 
      USA.
FAU - Jiang, Dawei
AU  - Jiang D
AD  - Department of Radiology, University of Wisconsin - Madison, Madison, WI, 53705, 
      USA.
AD  - Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, 
      Laboratory of Evolutionary Theranostics, School of Biomedical Engineering, Health 
      Science Center, Shenzhen University, Nanhai Ave 3688, Shenzhen, 518060, China.
FAU - England, Christopher G
AU  - England CG
AD  - Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, 
      53705, USA.
FAU - Barnhart, Todd E
AU  - Barnhart TE
AD  - Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, 
      53705, USA.
FAU - Yu, Bo
AU  - Yu B
AD  - Department of Radiology, University of Wisconsin - Madison, Madison, WI, 53705, 
      USA.
FAU - Rosenkrans, Zachary T
AU  - Rosenkrans ZT
AD  - School of Pharmacy, University of Wisconsin - Madison, Madison, WI, 53705, USA.
FAU - Wang, Rongfu
AU  - Wang R
AD  - Department of Nuclear Medicine, Peking University First Hospital, Beijing, 
      100034, China.
FAU - Engle, Jonathan W
AU  - Engle JW
AD  - Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, 
      53705, USA.
FAU - Xu, Xiaojie
AU  - Xu X
AD  - Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 
      Beijing, 100850, China. miraclexxj@126.com.
FAU - Huang, Peng
AU  - Huang P
AD  - Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, 
      Laboratory of Evolutionary Theranostics, School of Biomedical Engineering, Health 
      Science Center, Shenzhen University, Nanhai Ave 3688, Shenzhen, 518060, China. 
      peng.huang@szu.edu.cn.
FAU - Cai, Weibo
AU  - Cai W
AUID- ORCID: 0000-0003-4641-0833
AD  - Department of Radiology, University of Wisconsin - Madison, Madison, WI, 53705, 
      USA. wcai@uwhealth.org.
AD  - Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, 
      53705, USA. wcai@uwhealth.org.
AD  - School of Pharmacy, University of Wisconsin - Madison, Madison, WI, 53705, USA. 
      wcai@uwhealth.org.
AD  - University of Wisconsin Carbone Cancer Center, Madison, WI, 53705, USA. 
      wcai@uwhealth.org.
LA  - eng
GR  - 125246-RSG-13-099-01-CCE/American Cancer Society/International
GR  - JCYJ20160422091238319/Basic Research Program of Shenzhen/International
GR  - 1R01CA169365/EB/NIBIB NIH HHS/United States
GR  - 1R01EB021336/NH/NIH HHS/United States
GR  - 81401465/National Natural Science Foundation of China/International
GR  - P30 CA014520/CA/NCI NIH HHS/United States
GR  - Z171100001117024/Beijing Nova Program/International
GR  - 81441051/National Natural Science Foundation of China/International
GR  - T32 CA009206/CA/NCI NIH HHS/United States
GR  - P30CA014520/NH/NIH HHS/United States
GR  - T32CA009206/NH/NIH HHS/United States
GR  - R01 CA169365/CA/NCI NIH HHS/United States
GR  - 51573096/National Natural Science Foundation of China/International
GR  - R01 EB021336/EB/NIBIB NIH HHS/United States
GR  - JCYJ20170412111100742/Basic Research Program of Shenzhen/International
GR  - Z141107002514159/Beijing Capital Special Development Application 
      Program/International
PT  - Journal Article
DEP - 20180215
PL  - Germany
TA  - Eur J Nucl Med Mol Imaging
JT  - European journal of nuclear medicine and molecular imaging
JID - 101140988
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Radioisotopes)
RN  - 4Z63YK6E0E (daratumumab)
RN  - C6V6S92N3C (Zirconium)
RN  - EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
RN  - NTM296JU95 (Zirconium-89)
SB  - IM
MH  - ADP-ribosyl Cyclase 1/*metabolism
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacokinetics
MH  - Cell Line, Tumor
MH  - Lymphoma/*diagnostic imaging
MH  - Mice
MH  - Mice, Nude
MH  - Positron-Emission Tomography
MH  - Radioisotopes
MH  - Tissue Distribution
MH  - Zirconium
PMC - PMC5994170
MID - NIHMS932278
OTO - NOTNLM
OT  - 89Zr
OT  - B-cell lymphoma
OT  - CD38
OT  - Cancer
OT  - Daratumumab
OT  - ImmunoPET
OT  - Positron emission tomography (PET)
COIS- Conflict of Interest: The authors declare that they have no conflict of interest.
EDAT- 2018/02/17 06:00
MHDA- 2018/12/18 06:00
PMCR- 2019/07/01
CRDT- 2018/02/17 06:00
PHST- 2017/10/19 00:00 [received]
PHST- 2018/01/04 00:00 [accepted]
PHST- 2018/02/17 06:00 [pubmed]
PHST- 2018/12/18 06:00 [medline]
PHST- 2018/02/17 06:00 [entrez]
PHST- 2019/07/01 00:00 [pmc-release]
AID - 10.1007/s00259-018-3941-3 [pii]
AID - 10.1007/s00259-018-3941-3 [doi]
PST - ppublish
SO  - Eur J Nucl Med Mol Imaging. 2018 Jul;45(8):1372-1381. doi: 
      10.1007/s00259-018-3941-3. Epub 2018 Feb 15.