D-galactose receptor-targeted in vivo spectral fluorescence imaging of peritoneal metastasis using galactosamin-conjugated serum albumin-rhodamine green.
The wavelength resolved spectral fluorescence imaging technique using a fluorescein-conjugated avidin has been reported to visualize submillimeter implants of ovarian cancer because of its highly targeted and quickly cleared pharmacokinetics. However, clinical application of avidin was hampered by its strong immunogenicity. As a clinically feasible alternative to avidin, which targets the same D-galactose receptor but is made from a nonimmunogenic source, with even better binding capability by multiplying binding sites but still maintaining a favorable characteristic of high isoelectric point, a serum albumin conjugated with 23 galactosamine and 2 rhodamine green molecules (GmSA-RhodG) was designed and synthesized. GmSA-RhodG showed more than 10-fold rapid and higher uptake by SHIN3 ovarian cancer cells than both avidin- and no galactosamine-conjugated albumin (bovine serum)-RhodG. Sensitivity and specificity of GmSA-RhodG to detect red fluorescence labeled peritoneal cancer foci in mouse cancer model were 100%/99% (n=566), respectively for approximately 1-mm lesions and even smaller lesions were detected in vivo. These results indicate that GmSA-RhodG is not only a clinically feasible alternative but more efficient targeting reagent for D-galactose receptors than avidin-RhodG.
Hama
Yukihiro
Y
National Institutes of Health, National Cancer Institute, Center for Cancer Research, Molecular Imaging Program, Bethesda, Maryland 20892-1088, USA.
Urano
Yasuteru
Y
Koyama
Yoshinori
Y
Choyke
Peter L
PL
Kobayashi
Hisataka
H
D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005688:Galactosamine / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012235:Rhodamines / Q000493:pharmacokinetics; D012709:Serum Albumin / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence / Q000379:methods*
D005456:Fluorescent Dyes; D011956:Receptors, Cell Surface; D012235:Rhodamines; D012709:Serum Albumin; C039707:galactose receptor; D005688:Galactosamine