title: Carbon-11 labeled cathepsin K inhibitors: syntheses and preliminary in vivo evaluation.
abstract: Cathepsin K is a cysteine peptidase primarily located in osteoclasts, cells involved in normal growth and remodeling of bone but that are also responsible for bone loss in osteolytic diseases such as osteoporosis. In vivo imaging of cathepsin K may provide a method to assess changes in osteoclast numbers in such disease states. To that end, two high-affinity and selective cathepsin K inhibitors were radiolabeled with carbon-11. In vivo microPET imaging studies demonstrated uptake and prolonged retention of radioactivity in actively growing or remodeling bone regions (e.g., distal ulnar, carpal, distal and proximal humeral, distal femur, proximal tibia, tail vertebrae). Uptake into bone could be blocked by pre- or co-injection of unlabeled ligand, supporting a specific and saturable binding mechanism for radiotracer localization. These proof-of-concept studies indicate that radiolabeled cathepsin K inhibitors may have potential as in vivo imaging radiotracers for assessing changes of osteoclast numbers in osteolytic diseases.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, and Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Rodnick
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, and Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Xia
authors.initials: X
authors.lastname: Shao
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, and Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Kozloff
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, and Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Scott
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, and Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI 48109. Electronic address: mkilbour@umich.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kilbourn
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002250:Carbon Radioisotopes; D056657:Cathepsin K / Q000037:antagonists & inhibitors*; D005260:Female; D007553:Isotope Labeling; D049268:Positron-Emission Tomography; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011854:Radiochemistry; D051381:Rats
chemical_list: D002250:Carbon Radioisotopes; D011480:Protease Inhibitors; D056657:Cathepsin K
keywords: Bone; Cathepsin; Osteoclast