title: Fluorescence imaging of the lymph node uptake of proteins in mice after subcutaneous injection: molecular weight dependence.
abstract: OBJECTIVE
  To use noninvasive fluorescence imaging to investigate the influence of molecular weight (MW) of proteins on the rate of loss from a subcutaneous (SC) injection site and subsequent uptake by the draining lymph nodes in mice.
  
  
  METHODS
  Bevacizumab (149 kDa), bovine serum albumin (BSA, 66 kDa), ovalbumin (44.3 kDa) or VEGF-C156S (23 kDa), labeled with the near infrared dye IRDye 680, were injected SC into the front footpad of SKH-1 mice. Whole body non-invasive fluorescence imaging was performed to quantitate the fluorescence signal at the injection site and in axillary lymph nodes.
  
  
  RESULTS
  The half-life values, describing the times for 50% loss of proteins from the injection site, were 6.81 h for bevacizumab, 2.85 h for BSA, 1.57 h for ovalbumin and 0.31 h for VEGF-C156S. The corresponding axillary lymph node exposure, represented as the area of the % dose versus time curve, was 6.27, 5.13, 4.06 and 1.54% dose ∙ h, respectively.
  
  
  CONCLUSIONS
  Our results indicate that the rate of loss of proteins from a SC injection site is inversely related to MW of proteins, while lymph node exposure is proportionally related to the MW of proteins in a mouse model.
authors.affiliation: Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 517 Hochstetter Hall, Amherst, New York 14260, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.forename: Suraj G
authors.initials: SG
authors.lastname: Bhansali
authors.forename: Wing Cheung
authors.initials: WC
authors.lastname: Law
authors.forename: Earl J
authors.initials: EJ
authors.lastname: Bergey
authors.forename: Paras N
authors.initials: PN
authors.lastname: Prasad
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Morris
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068258:Bevacizumab; D002417:Cattle; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000032:analysis; D006207:Half-Life; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008970:Molecular Weight; D010047:Ovalbumin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013050:Spectrometry, Fluorescence; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051598:Whole Body Imaging
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005456:Fluorescent Dyes; D042461:Vascular Endothelial Growth Factor A; D012710:Serum Albumin, Bovine; D000068258:Bevacizumab; D010047:Ovalbumin