Fluorescence imaging of the lymph node uptake of proteins in mice after subcutaneous injection: molecular weight dependence

Pharm Res. 2012 Jul;29(7):1843-53. doi: 10.1007/s11095-012-0708-6. Epub 2012 Feb 29.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Bevacizumab
  • Cattle
  • Fluorescence
  • Fluorescent Dyes / analysis
  • Half-Life
  • Injections, Subcutaneous
  • Lymph Nodes / metabolism*
  • Male
  • Mice
  • Molecular Weight
  • Ovalbumin / administration & dosage
  • Ovalbumin / pharmacokinetics*
  • Serum Albumin, Bovine / administration & dosage
  • Serum Albumin, Bovine / pharmacokinetics*
  • Spectrometry, Fluorescence
  • Vascular Endothelial Growth Factor A / administration & dosage
  • Vascular Endothelial Growth Factor A / pharmacokinetics*
  • Whole Body Imaging

Substances

  • Antibodies, Monoclonal, Humanized
  • Fluorescent Dyes
  • Vascular Endothelial Growth Factor A
  • Serum Albumin, Bovine
  • Bevacizumab
  • Ovalbumin