Preclinical Evaluation of the Novel Monoclonal Antibody H6-11 for Prostate Cancer Imaging

Abstract

The biological properties of the novel monoclonal antibody (mAb) H6-11 and its potential utility for oncological imaging studies were evaluated using <i>in vitro</i> and <i>in vivo</i> assays. Immunoreactivity of H6-11 to the human prostate cancer PC-3 cell line and solid tumor xenografts was initially demonstrated using immunofluorescence staining; the specificity of H6-11 for prostate cancer was further evaluated using a commercial array of human prostate cancer and normal tissue samples (<i>n</i> = 49) in which H6-11 detected 95% of prostate adenocarcinomas. The <i>K</i>_d value of 61.7 ± 30 nM was determined using ¹²⁵I-labeled H6-11. Glycosylation analysis suggested the antigenic epitope of the glycan is an O-linked β-<i>N</i>-acetylglucoside (<i>O</i>-GlcNAc) group. Imaging studies of PC-3 tumor-bearing mice were performed using both optical imaging with NIR fluorescent dye-labeled H6-11 and microPET imaging with ⁸⁹Zr-labeled H6-11. These <i>in vivo</i> studies revealed that the labeled probes accumulated in PC-3 tumors 48–72 h postinjection, although significant retention in liver was also observed. By 120 h postinjection, the tumors were still evident, although the liver showed significant clearance. These studies suggest that the mAb H6-11 may be a useful tool to detect prostate cancer <i>in vitro</i> and <i>in vivo</i>