Molecular Imaging and Biology

, Volume 14, Issue 4, pp 472–479

High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas

  • Kimberley S. Samkoe
  • Kristian Sexton
  • Kenneth M. Tichauer
  • Shannon K. Hextrum
  • Omar Pardesi
  • Scott C. Davis
  • Julia A. O’Hara
  • P. Jack Hoopes
  • Tayyaba Hasan
  • Brian W. Pogue
Research Article

DOI: 10.1007/s11307-011-0503-5

Cite this article as:
Samkoe, K.S., Sexton, K., Tichauer, K.M. et al. Mol Imaging Biol (2012) 14: 472. doi:10.1007/s11307-011-0503-5

Abstract

Purpose

Cellular receptor targeted imaging agents present the potential to target extracellular molecular expression in cancerous lesions; however, the image contrast in vivo does not reflect the magnitude of overexpression expected from in vitro data. Here, the in vivo delivery and binding kinetics of epidermal growth factor receptor (EGFR) was determined for normal pancreas and AsPC-1 orthotopic pancreatic tumors known to overexpress EGFR.

Procedures

EGFR in orthotopic xenograft AsPC-1 tumors was targeted with epidermal growth factor (EGF) conjugated with IRDye800CW. The transfer rate constants (ke,K12, k21, k23, and k32) associated with a three-compartment model describing the vascular delivery, leakage rate and binding of targeted agents were determined experimentally. The plasma excretion rate, ke, was determined from extracted blood plasma samples. K12, k21, and k32 were determined from ex vivo tissue washing studies at time points ≥24 h. The measured in vivo uptake of IRDye800CW-EGF and a non-targeted tracer dye, IRDye700DX-carboxylate, injected simultaneously was used to determined k23.

Results

The vascular exchange of IRDye800CW-EGF in the orthotopic tumor (K12 and k21) was higher than in the AsPC-1 tumor as compared to normal pancreas, suggesting that more targeted agent can be taken up in tumor tissue. However, the cellular associated (binding) rate constant (k23) was slightly lower for AsPC-1 pancreatic tumor (4.1 × 10−4 s−1) than the normal pancreas (5.5 × 10−4 s−1), implying that less binding is occurring.

Conclusions

Higher vascular delivery but low cellular association in the AsPC-1 tumor compared to the normal pancreas may be indicative of low receptor density due to low cellular content. This attribute of the AsPC-1 tumor may indicate one contributing cause of the difficulty in treating pancreatic tumors with cellular targeted agents.

Key words

Three-compartment modelEpidermal growth factor receptorPancreatic tumorFluorescence imagingCellular associated rate constant

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2011

Authors and Affiliations

  • Kimberley S. Samkoe
    • 1
  • Kristian Sexton
    • 1
  • Kenneth M. Tichauer
    • 1
  • Shannon K. Hextrum
    • 1
  • Omar Pardesi
    • 1
  • Scott C. Davis
    • 1
  • Julia A. O’Hara
    • 1
  • P. Jack Hoopes
    • 1
    • 2
  • Tayyaba Hasan
    • 3
  • Brian W. Pogue
    • 1
    • 2
    • 3
  1. 1.Thayer School of EngineeringDartmouth CollegeHanoverUSA
  2. 2.Department of SurgeryDartmouth Medical SchoolHanoverUSA
  3. 3.Wellman Center for PhotomedicineMassachusetts General HospitalBostonUSA