Facile, Efficient Conjugation of a Trifunctional Lanthanide Chelate to a Peripheral Benzodiazepine Receptor Ligand

Abstract

[reaction: see text] Receptor-mediated imaging and therapy of diseased tissue is rapidly gaining favor in the medical community. The synthesis and facile aqueous/organic coupling of a peripheral-type benzodiazepine receptor ligand to a cyclen-based fluorophore is described herein. The contrast agent QM-CTMC-PK11195, when chelated with lanthanides, produces bright luminescence and good MRI contrast and can potentially serve as an imaging and demarcation agent for certain types of cancers.

Targeted Imaging of Colonic Tumors in Smad3−/− Mice Discriminates Cancer and Inflammation

“…To develop an optical imaging agent capable of rapid and high-throughput imaging of deep-tissue PBR-expressing tumors, we labeled our novel analogue of the PBR ligand, con-PK11195 (16,17), with a NIR fluorophore yielding the molecular imaging agent NIR-conPK11195 (Fig. 1A).…”

“…Con-PK11195 was synthesized as described previously (16). LI-COR-800CW was purchased from LI-COR Biosciences (Lincoln, NE).…”

“…The PBR synthetic ligand, PK11195, has been used clinically to image inflammation associated with several neurologic diseases (13)(14)(15). Con-PK11195, an analogue of the widely used PBR ligand PK11195, was recently prepared (16) and shown to be useful as a targeting agent for fluorescent probes as well as bimodal lanthanide chelate-imaging agents (17).…”

Molecular Imaging of the Translocator Protein (TSPO) in a Pre-Clinical Model of Breast Cancer

“…As a complementary approach to breast cancer imaging, our laboratory has developed molecular imaging agents that target the TSPO [39,41,43,44,47]. The TSPO is involved in a number of cellular processes and is upregulated in a variety of neurodegenerative diseases and cancers, including breast cancer [30][31][32][33][34][35][36][37].…”

“…NIR-conPK11195 was synthesized as previously described [38] by coupling the IRDye™ 800CW NHS ester dye to the conjugable form of PK 11195 developed in our laboratory (conPK11195; [39]). Briefly, IRDye™ 800CW NHS ester (2 mg, 1.7 μmol) and conPK11195 (2.5 mg, 6.6 μmol) were mixed in DMSO (5 mL) in a round bottom flask and stirred under argon flow for 1 h. The reaction was monitored using high-performance liquid chromatography (HPLC) analysis on a Varian Polaris C-18 column (250×4.6 mm) at a flow rate of 0.8 mL/min.…”