Targeted optical fluorescence imaging of human ovarian adenocarcinoma using a galactosyl serum albumin-conjugated fluorophore.
Achieving maximal cytoreduction during surgery is a critical prognostic factor for women with advanced-stage ovarian cancer. Targeting optical imaging agents directly to ovarian cancer cells by attaching them to galactosyl (galactosamine-conjugated) serum albumin, whose sugar residues bind surface lectins that are expressed in certain ovarian adenocarcinomas, may improve metastatic tumor identification and resection. Thus, we sought to demonstrate that galactosyl serum albumin-conjugated fluorophores would be a robust mechanism through which to target ovarian cancer by evaluating its tumor-targeting capability in nine human ovarian adenocarcinoma cell lines. The optical fluorophore rhodamine green was conjugated to galactosyl serum albumin, a non-immunogenic targeting molecule. Galactosyl serum albumin-rhodamine green's ability to target nine human ovarian adenocarcinoma cell lines was evaluated by flow cytometry, fluorescence microscopy and in vivo optical fluorescence imaging using female athymic nu/nu mice. All nine cell lines tested bound galactosyl serum albumin-rhodamine green more effectively than non-glycosylated controls (P < 0.0001). Fluorescence microscopy demonstrated that galactosyl serum albumin-rhodamine green was internalized into each cell line in a galactosamine-dependent manner. In vivo optical fluorescence images of intraperitoneal tumor-bearing mice acquired 3 h after intraperitoneal injection of galactosyl serum albumin-rhodamine green successfully differentiated between tumor and normal tissue. This technique also allowed the visualization of submillimeter-sized ovarian tumor implants. These results indicate that galactosyl serum albumin-rhodamine green can selectively target a variety of human ovarian adenocarcinomas for optical fluorescence imaging and thus may improve intraoperative tumor detection and resection.
Gunn
Andrew J
AJ
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD 20892-1088, USA.
Hama
Yukihiro
Y
Koyama
Yoshinori
Y
Kohn
Elise C
EC
Choyke
Peter L
PL
Kobayashi
Hisataka
H
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005688:Galactosamine; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000473:pathology*; D012710:Serum Albumin, Bovine; D013050:Spectrometry, Fluorescence; D014183:Transplantation, Heterologous