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

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>

Copper Loading of Preformed Nanoparticles for PET-Imaging Applications

Nanoparticles (NP) are promising contrast agents for positron emission tomography (PET) radionuclide imaging that can increase signal intensity by localizing clusters of PET radionuclides together. However, methods to load NPs with PET radionuclides suffer from harsh loading conditions or poor loading efficacies or result in NP surface modifications that alter targeting in vivo. We present the formation of water-dispersible, polyethylene glycol coated NPs that encapsulate phthalocyanines into NP cores at greater than 50 wt % loading, using the self-assembly technique Flash NanoPrecipitation. Particles from 70 to 160 nm are produced. Phthalocyanine NPs rapidly and spontaneously chelate metals under mild conditions and can act as sinks for PET radionuclides such as 64-Cu to produce PET-active NPs. NPs chelate copper­(II) with characteristic rates of 1845 M^–1 h^–1 at pH 6 and 37 °C, which produced >90% radionuclide chelation within 1 h. NP physical properties, such as core composition, core fluidity, and size, can be tuned to modulate chelation kinetics. These NPs retain ⁶⁴Cu even in the presence of the strong chelator ethylene diamine tetraacetic acid. The development of these constructs for rapid and facile radionuclide labeling expands the applications of NP-based PET imaging