Yukihiro Hama MD, Presenter: Nothing to Disclose

Yasuteru Urano PhD, Abstract Co-Author: Nothing to Disclose

Yoshinori Koyama MD, Abstract Co-Author: Nothing to Disclose

Marcelino Bernardo, Abstract Co-Author: Nothing to Disclose

Peter L. Choyke MD, Abstract Co-Author: Researcher, General Electric Company Researcher, Koninklijke Philips Electronics NV Researcher, Becton, Dickinson and Company Researcher, Siemens AG

Hisataka Kobayashi MD, PhD, Abstract Co-Author: Nothing to Disclose

Activatable optical probes provide very high target to background ratios. One strategy is to use a self-quenched avidin-rhodamineX conjugate in which fluorophores are activated only after cellular internalization, however, avidin is too immunogenic to permit use in humans. We propose a more clinically feasible alternative to avidin, galactosamine-conjugated serum albumin (GmSA) labeled with activatable self-quenched rhodamineX, which targets the D-galactose receptor with higher binding affinity than avidin but which is not immunogenic.

We synthesized a self-quenched GmSA-rhodamineX conjugate (GmSA-20ROX) and a non-quenched GmSA-rhodamineX conjugate (GmSA-1ROX). The fluorescence intensity of GmSA-1ROX was higher than that of GmSA-20ROX in phosphate buffer at pH 7.4. Intraperitoneal metastases of SHIN3 ovarian cancer cells were established after intraperitoneal implantation. Scans were obtained 0-3 hours after incubation with GmSA-20ROX or GmSA-1ROX. Spectral fluorescence imaging was obtained with the Maestro CRi camera on in situ and dissected specimens.

Incubation of peritoneal metastases with GmSA-20ROX produced up to a 5-fold increase in fluorescence signal by intracellular processing on flow cytometry. Submillimeter cancer nodules in the peritoneum were readily identified with minimal background signal. Sensitivity and specificity of GmSA-20ROX to detect red fluorescence labeled peritoneal cancer foci in mouse model were 99%/99% respectively (n = 336), whereas those of GmSA-1ROX were 24%/100% (n = 388), respectively for lesions ~0.8 mm or greater in diameter.

Activatable GmSA-20ROX is not only a clinically feasible alternative to avidin but is a highly sensitive targeting reagent for D-galactose receptors allowing the detection of ovarian cancer microfoci.

This lectin-targeted activatable fluorescence imaging technique may help surgeons to detect and treat peritoneal cancer metastases that might otherwise be missed by conventional visualization.

Hama, Y, Urano, Y, Koyama, Y, Bernardo, M, Choyke, P, Kobayashi, H, Target Cell Specific Activatable in Vivo Molecular Imaging Using a Clinically Feasible Galactosamin-conjugated Serum Albumin-RhodamineX Conjugate.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5004946.html