A Peripheral Benzodiazepine Receptor Targeted Agent for In Vitro Imaging and Screening

• Published in: Bioconjugate chemistry Vol. 17; no. 3; pp. 735 - 740
• Main Authors: Manning, H. Charles, Smith, Sarah M, Sexton, Michelle, Haviland, Sarah, Bai, Mingfeng, Cederquist, Kristin, Stella, Nephi, Bornhop, Darryl J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.05.2006
• Subjects: Animals; Binding sites; Breast cancer; Cell Line; Cells; Humans; Isoquinolines - chemical synthesis; Isoquinolines - chemistry; Isoquinolines - pharmacology; Medical imaging; Mitochondria - drug effects; Mitochondria - enzymology; Molecular Structure; Proteins; Rats; Receptors, GABA - metabolism; Succinate Dehydrogenase - metabolism
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc060020b

We developed a molecular imaging agent (MIA), a conjugable form of PK11195 (conPK11195) coupled to a lissamine dye (Liss−ConPK11195), which targets the peripheral benzodiazepine receptor (PBR). To determine that our compound specifically binds to this 18 kDa protein, primarily expressed on the mitochondria, we performed classic binding studies on live MDA-MB-231 breast cancer cells and measured fluorescence in cell fractions of C6 glioma cells. We found that conPK11195 conjugated to the fluorophore retained significant binding to its target. Here we demonstrate the utility of the agent for in vitro imaging of live cells by specific binding to the protein of interest.