title: Side-by-Side Comparison of Commonly Used Biomolecules That Differ in Size and Affinity on Tumor Uptake and Internalization.
abstract: The ability to use a systemically injected agent to image tumor is influenced by tumor characteristics such as permeability and vascularity, and the size, shape, and affinity of the imaging agent. In this study, six different imaging biomolecules, with or without specificity to tumor, were examined for tumor uptake and internalization at the whole body, ex-vivo tissue, and cellular levels: antibodies, antibody fragments (Fab), serum albumin, and streptavidin. The time of peak tumor uptake was dependent solely on the size of molecules, suggesting that molecular size is the major factor that influences tumor uptake by its effect on systemic clearance and diffusion into tumor. Affinity to tumor antigen failed to augment tumor uptake of Fab above non-specific accumulation, which suggests that Fab fragments of typical monoclonal antibodies may fall below an affinity threshold for use as molecular imaging agents. Despite abundant localization into the tumor, albumin and streptavidin were not found on cell surface or inside cells. By comparing biomolecules differing in size and affinity, our study highlights that while pharmacokinetics are a dominant factor in tumor uptake for biomolecules, affinity to tumor antigen is required for tumor binding and internalization.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, United States of America; National Nanotechnology Center, National Science and Technology Development Agency, Pathumthani 12120, Thailand.
authors.forename: Jeerapond
authors.initials: J
authors.lastname: Leelawattanachai
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, NY 10065, United States of America.
authors.forename: Keon-Woo
authors.initials: KW
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, United States of America.
authors.forename: Praveesuda
authors.initials: P
authors.lastname: Michael
authors.affiliation: Department of Radiology, Weill Cornell Medical College, New York, NY 10065, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Ting
authors.affiliation: Department of Advanced Materials Engineering, Kangwon National University, Samcheok, South Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, United States of America; Department of Radiology, Weill Cornell Medical College, New York, NY 10065, United States of America; Department of Biomedical Engineering, Dongguk University, Seoul 100-715, South Korea.
authors.forename: Moonsoo M
authors.initials: MM
authors.lastname: Jin
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging; D004705:Endocytosis; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016513:Mice, SCID; D008954:Models, Biological; D008970:Molecular Weight; D009369:Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D051598:Whole Body Imaging; D023041:Xenograft Model Antitumor Assays
chemical_list: D007074:Immunoglobulin G; D011506:Proteins; D018799:Intercellular Adhesion Molecule-1