COMMUNICATIONS Dark Quenched Matrix Metalloproteinase Fluorogenic Probe for Imaging Osteoarthritis Development in ViWo Seulki Lee, †,§ Kyeongsoon Park, †,§ Seung-Young Lee, † Ju Hee Ryu, † Jong Woong Park, ‡ Hyung Jun Ahn, † Ick Chan Kwon, † In-Chan Youn, † Kwangmeyung Kim, †, * and Kuiwon Choi †, * Biomedical Research Center, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, South Korea, Department of Orthopaedic Surgery, College of Medicine, Korea University, Danwon-Gu, Ansan, Gyeonggi, South Korea. Received June 30, 2008; Revised Manuscript Received July 24, 2008 The early detection of osteoarthritis (OA) is currently a key challenge in the field of rheumatology. Biochemical studies of OA have indicated that matrix metalloproteinase-13 (MMP-13) plays a central role in cartilage degradation. In this study, we describe the potential use of a dark-quenched fluorogenic MMP-13 probe to image MMP-13 in both in Vitro and rat models. The imaging technique involved using a MMP-13 peptide substrate, near-infrared (NIR) dye, and a NIR dark quencher. The results from this study demonstrate that the use of a dark-quenched fluorogenic probe allows for the visual detection of MMP-13 in Vitro and in OA-induced rat models. In particular, by targeting this OA biomarker, the symptoms of the early and late stages of OA can be readily monitored, imaged, and analyzed in a rapid and efficient fashion. We anticipate that this simple and highly efficient fluorogenic probe will assist in the clinical management of patients with OA, not only for early diagnosis but also to assess individual patient responses to new drug treatments. Degenerative joint diseases including osteoarthritis (OA) are common, particularly in the elderly. General awareness of OA is low because this condition is typically considered to be an effect of aging. The initial stages of OA are clinically silent. Therefore, people may have the disease for years with no symptoms, and when symptoms do occur, the disease has often already reached an advanced stage. However, if it was possible to monitor and assess the disease states of OA, treatment could begin before significant damage occurs. For these reasons, early detection of OA is a key challenge in the field of rheumatology. The challenges posed in identifying OA are the detection of both early and subtle changes of joint and articular cartilage. Early signs of OA are characterized by the progressive loss of proteoglycan aggrecan, which is reflected by excessive damage to type II collagen. A decrease in proteoglycan aggrecan ultimately results in the loss of articular cartilage (1). X-rays and computed tomography (CT) can show large changes in a joint based on bone density; however, these techniques do not reveal detailed surface information (2). Although magnetic resonance imaging (MRI) (3) and ultrasound (US) (4) techniques recently provided both surface and internal details of articular † Biomedical Research Center, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, South Korea. ‡ Department of Orthopaedic Surgery, College of Medicine, Korea University, Danwon-Gu, Ansan, Gyeonggi, South Korea. § These authors contributed equally to this work. * To whom correspondence should be addressed. Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Korea. Tel: +82-2-958-5912. Fax: +82-2-958-5909. E-mail: kim@kist.re.kr and choi@kist.re.kr. SEPTEMBER 2008 Volume 19, Number 9  Copyright 2008 by the American Chemical Society 10.1021/bc800264z CCC: $40.75  2008 American Chemical Society Published on Web 08/26/2008