title: PET imaging of64Cu-DOTA-scFv-anti-PSMA lipid nanoparticles (LNPs): Enhanced tumor targeting over anti-PSMA scFv or untargeted LNPs.
abstract: BACKGROUND
  Single chain (scFv) antibodies are ideal targeting ligands due to their modular structure, high antigen specificity and affinity. These monovalent ligands display rapid tumor targeting but have limitations due to their fast urinary clearance.
  
  
  METHODS
  An anti-prostate membrane antigen (PSMA) scFv with a site-specific cysteine was expressed and evaluated in a prostate cancer xenograft model by Cu-64 PET imaging. To enhance tumor accumulation, the scFv-cys was conjugated to the co-polymer DSPE-PEG-maleimide that spontaneously assembled into a homogeneous multivalent lipid nanoparticle (LNP).
  
  
  RESULTS
  The targeted LNP exhibited a 2-fold increase in tumor uptake compared to the scFv alone using two different thiol ester chemistries. The anti-PSMA scFv-LNP exhibited a 1.6 fold increase in tumor targeting over the untargeted LNP.
  
  
  CONCLUSIONS
  The targeted anti-PSMA scFv-LNP showed enhanced tumor accumulation over the scFv alone or the untargeted DOTA-micelle providing evidence for the development of this system for drug delivery.
  
  
  CONCLUSIONS
  Anti-tumor scFv antibody fragments have not achieved their therapeutic potential due to their fast blood clearance. Conjugation to an LNP enables multivalency to the tumor antigen as well as increased molecular size for chemotherapy drug delivery.
authors.affiliation: Department of Radiation Oncology, City of Hope Medical Center, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: Patty
authors.initials: P
authors.lastname: Wong
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: Junie
authors.initials: J
authors.lastname: Chea
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Delgado
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: Desiree
authors.initials: D
authors.lastname: Crow
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: Erasmus
authors.initials: E
authors.lastname: Poku
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Szpikowska
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bowles
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Channappa
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: David
authors.initials: D
authors.lastname: Colcher
authors.affiliation: Department of Radiation Oncology, City of Hope Medical Center, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: Jeffrey Y C
authors.initials: JYC
authors.lastname: Wong
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Shively
authors.affiliation: Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA. Electronic address: pyazaki@coh.org.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Yazaki
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003301:Copper Radioisotopes; D004337:Drug Carriers / Q000737:chemistry; D043425:Glutamate Carboxypeptidase II / Q000276:immunology*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D057127:Single-Chain Antibodies / Q000737:chemistry* / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D003301:Copper Radioisotopes; D004337:Drug Carriers; D006573:Heterocyclic Compounds, 1-Ring; D057127:Single-Chain Antibodies; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: Lipid nanoparticles; Polyethylene glycol; Positron emission tomography; Prostate cancer; Single-chain antibody