PMID- 18413392
OWN - NLM
STAT- MEDLINE
DCOM- 20080721
LR  - 20211020
IS  - 0161-5505 (Print)
IS  - 1535-5667 (Electronic)
IS  - 0161-5505 (Linking)
VI  - 49
IP  - 5
DP  - 2008 May
TI  - Small-animal PET imaging of human epidermal growth factor receptor type 2 
      expression with site-specific 18F-labeled protein scaffold molecules.
PG  - 804-13
LID - 10.2967/jnumed.107.047381 [doi]
AB  - Human epidermal growth factor receptor type 2 (HER2) is a well-established tumor 
      biomarker that is overexpressed in a wide variety of cancers and that serves as a 
      molecular target for therapeutic intervention. HER2 also serves as a prognostic 
      indicator of patient survival and as a predictive marker of the response to 
      antineoplastic therapy. The development of (18)F-labeled biomolecules for PET 
      imaging of HER2 (HER2 PET) is very important because it may provide a powerful 
      tool for the early detection of HER2-positive tumor recurrence and for the 
      monitoring of HER2-based tumor treatment. METHODS: In this study, anti-HER2 
      monomeric and dimeric protein scaffold molecules [Z(HER2:477) and 
      (Z(HER2:477))(2), respectively] were radiofluorinated at a reasonable 
      radiochemical yield (13%-18%) by use of site-specific oxime chemistry. The 
      resulting radiofluorinated protein scaffold molecules were then evaluated as 
      potential molecular probes for small-animal HER2 PET by use of a SKOV3 
      tumor-bearing mouse model. RESULTS: The 4-(18)F-fluorobenzaldehyde conjugated 
      aminooxy-protein scaffolds [(18)F-N-(4-fluorobenzylidene)oxime (FBO)-Z(HER2:477) 
      and (18)F-FBO-(Z(HER2:477))(2)] both displayed specific HER2-binding ability in 
      vitro. Biodistribution and small-animal PET imaging studies further revealed that 
      (18)F-FBO-Z(HER2:477) showed rapid and high SKOV3 tumor accumulation and quick 
      clearance from normal tissues, whereas (18)F-FBO-(Z(HER2:477))(2) showed poor in 
      vivo performance (low tumor uptake and tumor-to-normal tissue ratios). The 
      specificity of (18)F-FBO-Z(HER2:477) for SKOV3 tumors was confirmed by its lower 
      uptake on pretreatment of tumor-bearing mice with the HER2-targeting agents 
      Z(HER2) and trastuzumab. Moreover, small-animal PET imaging studies revealed that 
      (18)F-FBO-Z(HER2:477) produced higher-quality tumor imaging than 
      (18)F-FBO-(Z(HER2:477))(2). (18)F-FBO-Z(HER2:477) could clearly identify 
      HER2-positive tumors with good contrast. CONCLUSION: Overall, these data 
      demonstrate that (18)F-FBO-Z(HER2:477) is a promising PET probe for imaging HER2 
      expression in living mice. It has a high potential for translation to clinical 
      applications. The radiofluorination method developed can also be used as a 
      general strategy for the site-specific labeling of other proteins with (18)F. The 
      protein scaffold molecules used here are attractive for the further development 
      of PET probes for other molecular targets.
FAU - Cheng, Zhen
AU  - Cheng Z
AD  - Molecular Imaging Program at Stanford, Department of Radiology, Bio-X Program, 
      Stanford University, Stanford, California 94305, USA.
FAU - De Jesus, Omayra Padilla
AU  - De Jesus OP
FAU - Namavari, Mohammad
AU  - Namavari M
FAU - De, Abhijit
AU  - De A
FAU - Levi, Jelena
AU  - Levi J
FAU - Webster, Jack Matt
AU  - Webster JM
FAU - Zhang, Rong
AU  - Zhang R
FAU - Lee, Brian
AU  - Lee B
FAU - Syud, Faisal A
AU  - Syud FA
FAU - Gambhir, Sanjiv Sam
AU  - Gambhir SS
LA  - eng
GR  - P50 CA114747/CA/NCI NIH HHS/United States
GR  - R24 CA092865/CA/NCI NIH HHS/United States
GR  - U54 CA119367/CA/NCI NIH HHS/United States
GR  - R24 CA93862/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080415
PL  - United States
TA  - J Nucl Med
JT  - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JID - 0217410
RN  - 0 (Fluorine Radioisotopes)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Dimerization
MH  - ErbB Receptors/*chemistry/genetics/*metabolism
MH  - Fluorine Radioisotopes
MH  - *Gene Expression Regulation
MH  - Halogenation
MH  - Humans
MH  - Mice
MH  - Neoplasms/diagnostic imaging
MH  - Positron-Emission Tomography/*methods
MH  - Protein Binding
MH  - Protein Structure, Quaternary
MH  - Radiochemistry
MH  - Recombinant Fusion Proteins
MH  - Substrate Specificity
MH  - Tissue Distribution
PMC - PMC4154808
MID - NIHMS621552
EDAT- 2008/04/17 09:00
MHDA- 2008/07/22 09:00
PMCR- 2014/09/04
CRDT- 2008/04/17 09:00
PHST- 2008/04/17 09:00 [pubmed]
PHST- 2008/07/22 09:00 [medline]
PHST- 2008/04/17 09:00 [entrez]
PHST- 2014/09/04 00:00 [pmc-release]
AID - jnumed.107.047381 [pii]
AID - 10.2967/jnumed.107.047381 [doi]
PST - ppublish
SO  - J Nucl Med. 2008 May;49(5):804-13. doi: 10.2967/jnumed.107.047381. Epub 2008 Apr 
      15.