D-galactose receptor-targeted in vivo spectral fluorescence molecular imaging of peritoneal metastasis

BIOT 188

Hisataka Kobayashi, Kobayash@mail.nih.gov1, Yukihiro Hama, hamay@mail.nih.gov1, Andrew J Gunn1, Yoshinori Koyama1, Yasuteru Urano, urano@mol.f.u-tokyo.ac.jp2, and Peter L Choyke1. (1) Molecular Imaging Program, CCR, NCI/NIH, Building 10, Room 1B40 MSC 1088, 10 Center Drive, Bethesda, MD 20892-1088, (2) Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
The D-galactose receptor is a promising molecular target for imaging of peritoneal carcinomatosis. The ligands to the D-galactose receptor have high binding capacity yet also have rapid clearance pharmacokinetics from the peritoneal cavity and are bound to D-galactose receptors on hepatocytes. Optical agents targeted to the D-galactose receptor could help surgeons identify peritoneal metastases. A serum albumin conjugated with 23 galactosamine and 2 rhodamine green molecules (GmSA-RhodG) was designed as a clinically feasible alternative to a successful avidin-FITC reagent, which targets the same D-galactose receptor but is made from a non-immunogenic source, and has more favorable binding and isoelectric point characteristics than avidin and includes Rhodamine green which has better imaging features. GmSA-RhodG showed greater than 10-fold uptake by SHIN3 ovarian cancer cells than either avidin or serum albumin without galactosamine conjugation (BSA-RhodG.). Sensitivity and specificity of GmSA-RhodG were 100%/99% (n = 566), respectively for ~1 mm lesions in vivo.

 

Biophysical and Biomolecular Symposium: Targeted Delivery of Proteins & Nucleotides
8:00 AM-11:00 AM, Wednesday, August 22, 2007 BCEC -- 107 A/B, Oral

Division of Biochemical Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007