Fluorescent tumour imaging of type I IGF receptor in vivo: comparison of antibody-conjugated quantum dots and small-molecule fluorophore

Abstract

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 (smallmolecule 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. CONCLUSION: Taken together, our data suggest that small-molecule fluorophores, not QDs, are suitable to detect the expression and downregulation of IGF1R in vivo.

Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies

“…Cetuximab labeled with the NIR fluorescent dye Cy5.5 showed specific tumor uptake in head and neck squamous cell carcinoma xenografts (23), whereas the IGF-1R targeting antibody AVE-1642 labeled with the NIR fluorescent dye Alexa 680 was specifically taken up by the R-/IGF-1R xenograft tumor (24). Trastuzumab that was dual-labeled with 111 In-DTPA and IRDye 800CW showed a similar tumor-tomuscle ratio of 2.25 for fluorescence measurements and 2.66 in a SK-BR-3 luc1 model for SPECT (25).…”

“…This information adds to the recent data obtained for fluorescence-labeled antibodies targeting the epidermal growth factor receptor (EGFR), HER2, and the insulin-like growth factor receptor 1 (IGF-1R) (23)(24)(25)(26). Cetuximab labeled with the NIR fluorescent dye Cy5.5 showed specific tumor uptake in head and neck squamous cell carcinoma xenografts (23), whereas the IGF-1R targeting antibody AVE-1642 labeled with the NIR fluorescent dye Alexa 680 was specifically taken up by the R-/IGF-1R xenograft tumor (24).…”

A Review on Aptamer-Conjugated Quantum Dot Nanosystems for Cancer Imaging and Theranostic

“…Currently, QDs commonly are conjugated with antibodies for the labeling of cancer cells or tissues that overexpress specific cancer antigens [45,46]. Antibodies representing binding capacity to target antigens have been extensively utilized in the fields of cancer theranostic, but these methods have their own limitations including immunogenicity, incomplete target tissue penetration, long residence time in the blood stream, and being time consuming and costly in production process [47,48].…”

“…The initiation step of a common SELEX process is an artificially synthesized random DNA oligonucleotide library containing about 1013-1015 diverse sequences [45]. In the first round of SELEX process, the DNA or RNA pool is incubated with a specific target.…”

Polymersomes containing quantum dots for cellular imaging

“…8 Therefore, attempts have been made to improve the stability and promote cellular uptake of QDs using surface chemistry modifications. This includes the functionalization of QDs with biomolecules such as antibodies, 9 proteins, 10 or peptides, 11 as well as their coating with polymers or amphiphilic copolymers. 12,13 However, modification of the QD surface may significantly…”