title: Pretargeted Positron Emission Tomography Imaging That Employs Supramolecular Nanoparticles with in Vivo Bioorthogonal Chemistry.
abstract: A pretargeted oncologic positron emission tomography (PET) imaging that leverages the power of supramolecular nanoparticles with in vivo bioorthogonal chemistry was demonstrated for the clinically relevant problem of tumor imaging. The advantages of this approach are that (i) the pharmacokinetics (PKs) of tumor-targeting and imaging agents can be independently altered via chemical alteration to achieve the desired in vivo performance and (ii) the interplay between the two PKs and other controllable variables confers a second layer of control toward improved PET imaging. In brief, we utilized supramolecular chemistry to synthesize tumor-targeting nanoparticles containing transcyclooctene (TCO, a bioorthogonal reactive motif), called TCO⊂SNPs. After the intravenous injection and subsequent concentration of the TCO⊂SNPs in the tumors of living mice, a small molecule containing both the complementary bioorthogonal motif (tetrazine, Tz) and a positron-emitting radioisotope ((64)Cu) was injected to react selectively and irreversibly to TCO. High-contrast PET imaging of the tumor mass was accomplished after the rapid clearance of the unreacted (64)Cu-Tz probe. Our nanoparticle approach encompasses a wider gamut of tumor types due to the use of EPR effects, which is a universal phenomenon for most solid tumors.
authors.affiliation: Department of Medicinal and Applied Chemistry, Kaohsiung Medical University , 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.|Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), University of California, Los Angeles , Los Angeles, California 90095-1770, United States.
authors.forename: Shuang
authors.initials: S
authors.lastname: Hou
authors.affiliation: Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), University of California, Los Angeles , Los Angeles, California 90095-1770, United States.
authors.forename: Jin-Sil
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), University of California, Los Angeles , Los Angeles, California 90095-1770, United States.
authors.forename: Mitch Andre
authors.initials: MA
authors.lastname: Garcia
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California , Los Angeles, California 90033-9061, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), University of California, Los Angeles , Los Angeles, California 90095-1770, United States.
authors.forename: Kuan-Ju
authors.initials: KJ
authors.lastname: Chen
authors.affiliation: Department of Medicinal and Applied Chemistry, Kaohsiung Medical University , 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), University of California, Los Angeles , Los Angeles, California 90095-1770, United States.
authors.forename: Ziyue K
authors.initials: ZK
authors.lastname: Jiang
authors.affiliation: Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), University of California, Los Angeles , Los Angeles, California 90095-1770, United States.
authors.forename: Tracy
authors.initials: T
authors.lastname: Ro
authors.affiliation: Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), University of California, Los Angeles , Los Angeles, California 90095-1770, United States.
authors.forename: Lily
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), University of California, Los Angeles , Los Angeles, California 90095-1770, United States.
authors.forename: David B
authors.initials: DB
authors.lastname: Stout
authors.affiliation: Department of Surgery, University of California, Los Angeles , Los Angeles, California 90095, United States.
authors.forename: James S
authors.initials: JS
authors.lastname: Tomlinson
authors.affiliation: National Center for Nanoscience and Technology , 11 Beiyitiao Zhongguancun Haidian District, Beijing, 100190, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California , Los Angeles, California 90033-9061, United States.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), University of California, Los Angeles , Los Angeles, California 90095-1770, United States.
authors.forename: Hsian-Rong
authors.initials: HR
authors.lastname: Tseng
authors.affiliation: Department of Medicinal and Applied Chemistry, Kaohsiung Medical University , 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Lin
mesh_terms: D000818:Animals; D003301:Copper Radioisotopes / Q000008:administration & dosage / Q000737:chemistry; D034242:Cyclooctanes / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry; D005909:Glioblastoma / Q000175:diagnosis* / Q000000981:diagnostic imaging* / Q000473:pathology; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D007279:Injections, Subcutaneous; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009368:Neoplasm Transplantation; D010539:Permeability; D011095:Polyethylenes / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*; D014183:Transplantation, Heterologous
chemical_list: D003301:Copper Radioisotopes; D034242:Cyclooctanes; D050091:Dendrimers; D006573:Heterocyclic Compounds, 1-Ring; C104700:PAMAM Starburst; D011095:Polyethylenes
keywords: EPR effect; PET imaging; bioorthogonal chemistry; pretargeted; supramolecular nanoparticles