Fluorescent tumour imaging of type I IGF receptor in vivo: comparison of antibody-conjugated quantum dots and small-molecule fluorophore.
BACKGROUND
The type I insulin-like growth factor receptor (IGF1R) is a transmembrane tyrosine kinase involved in cancer proliferation, survival, and metastasis.


METHODS
In this study, we used two different fluorescent technologies (small-molecule fluorophores and quantum dot (QD) nanoparticles) to detect receptor expression and its downregulation by antibodies in vivo.


RESULTS
After conjugation with AVE-1642, a humanised anti-IGF1R monoclonal antibody, both QDs (705 nm) or Alexa 680 (small-molecule fluorophore) detected expression and downregulation of IGF1R in vitro. To examine their utility in vivo, either AVE-1642 conjugates were intravenously delivered to mice bearing xenograft tumours of mouse embryo fibroblasts expressing human IGF1R or MCF-7 human breast cancer cells. Quantum dot fluorescence was mainly localised to the reticuloendothelial system in several organs and engulfed by macrophages, with only very small amount of QDs detected in the xenograft tumours. Depletion of macrophages by clodronate liposomes did not alter the nonspecific uptake of QDs. In contrast, AVE-1642-conjugated Alexa 680 solely targeted to xenograft tumour and was able to detect IGF1R downregulation, with little nonspecific targeting to other tissues or organs in mice.


CONCLUSIONS
Taken together, our data suggest that small-molecule fluorophores, not QDs, are suitable to detect the expression and downregulation of IGF1R in vivo.
Zhang
H
H
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Zeng
X
X
Li
Q
Q
Gaillard-Kelly
M
M
Wagner
C R
CR
Yee
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D019085:Fluorescent Antibody Technique, Direct / Q000379:methods*; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000493:pharmacokinetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D045663:Quantum Dots; D017526:Receptor, IGF Type 1 / Q000032:analysis* / Q000096:biosynthesis; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D018796:Immunoconjugates; D017526:Receptor, IGF Type 1