PMID- 34439132
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210830
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 16
DP  - 2021 Aug 6
TI  - A Humanized Anti-GPC3 Antibody for Immuno-Positron Emission Tomography Imaging of 
      Orthotopic Mouse Model of Patient-Derived Hepatocellular Carcinoma Xenografts.
LID - 10.3390/cancers13163977 [doi]
LID - 3977
AB  - Glypican-3 (GPC3) is an attractive diagnostic marker for hepatocellular carcinoma 
      (HCC). We previously reported the potential of an (89)Zr-labeled murine anti-GPC3 
      antibody (clone 1G12) for immunoPET imaging of HCC in orthotopic patient-derived 
      xenograft (PDX) mouse models. We now humanized the murine antibody by 
      complementarity determining region (CDR) grafting, to allow its clinical 
      translation for human use. The engineered humanized anti-GPC3 antibody, clone 
      H3K3, retained comparable binding affinity and specificity to human GPC3. H3K3 
      was conjugated with desferrioxamine (Df) and radiolabeled with (89)Zr to produce 
      the PET/CT tracer (89)Zr-Df-H3K3. When injected into GPC3-expressing orthotopic 
      HCC PDX in NOD SCID Gamma (NSG) mice, (89)Zr-Df-H3K3 showed specific high uptake 
      into the orthotopic PDX and minimal, non-specific uptake into the non-tumor 
      bearing liver. Specificity was demonstrated by significantly higher uptake of 
      (89)Zr-Df-H3K3 into the non-blocked PDX mice, compared with the blocked PDX mice 
      (which received prior injection of 100 mg of unlabeled H3K3). Region of interest 
      (ROI) analysis showed that the PDX/non-tumor liver ratio was highest (mean +/- SD: 
      3.4 +/- 0.31) at 168 h post injection; this ratio was consistent with 
      biodistribution studies at the same time point. Thus, our humanized anti-GPC3 
      antibody, H3K3, shows encouraging potential for use as an immunoPET tracer for 
      diagnostic imaging of HCC patients.
FAU - Natarajan, Arutselvan
AU  - Natarajan A
AUID- ORCID: 0000-0002-9958-2623
AD  - Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X 
      Program, Stanford University, Stanford, CA 94305, USA.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Asian Liver Center, Department of Surgery, School of Medicine, Stanford, CA 
      94305, USA.
FAU - Ye, Wei
AU  - Ye W
AD  - Asian Liver Center, Department of Surgery, School of Medicine, Stanford, CA 
      94305, USA.
FAU - Huttad, Lakshmi
AU  - Huttad L
AD  - Asian Liver Center, Department of Surgery, School of Medicine, Stanford, CA 
      94305, USA.
FAU - Tan, Mingdian
AU  - Tan M
AUID- ORCID: 0000-0003-3064-2189
AD  - Asian Liver Center, Department of Surgery, School of Medicine, Stanford, CA 
      94305, USA.
FAU - Chua, Mei-Sze
AU  - Chua MS
AD  - Asian Liver Center, Department of Surgery, School of Medicine, Stanford, CA 
      94305, USA.
FAU - Gambhir, Sanjiv S
AU  - Gambhir SS
AD  - Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X 
      Program, Stanford University, Stanford, CA 94305, USA.
FAU - So, Samuel K
AU  - So SK
AD  - Asian Liver Center, Department of Surgery, School of Medicine, Stanford, CA 
      94305, USA.
LA  - eng
GR  - U54 CA199075/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20210806
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8391944
OTO - NOTNLM
OT  - glypican-3
OT  - hepatocellular carcinoma
OT  - humanized antibody
OT  - immunoPET imaging
COIS- The authors declare that they have no competing interests.
EDAT- 2021/08/28 06:00
MHDA- 2021/08/28 06:01
PMCR- 2021/08/06
CRDT- 2021/08/27 01:02
PHST- 2021/06/27 00:00 [received]
PHST- 2021/07/27 00:00 [revised]
PHST- 2021/08/04 00:00 [accepted]
PHST- 2021/08/27 01:02 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/08/28 06:01 [medline]
PHST- 2021/08/06 00:00 [pmc-release]
AID - cancers13163977 [pii]
AID - cancers-13-03977 [pii]
AID - 10.3390/cancers13163977 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Aug 6;13(16):3977. doi: 10.3390/cancers13163977.