cell cycle regulating kinase cdk4 as a potential target for tumor cell treatment and tumor imaging细胞周期调节激酶到作为一个潜在的目标肿瘤细胞治疗和肿瘤成像.pdfVIP

Hindawi Publishing Corporation Journal of Oncology Volume 2009, Article ID 106378, 12 pages doi:10.1155/2009/106378 Research Article Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging Franziska Graf,1 Lena Koehler,1 Torsten Kniess,1 Frank Wuest,2 Birgit Mosch,1 and Jens Pietzsch1 1 Research Center Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, Germany 2 Department of Oncologic Imaging, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton AB, Canada T6G 1Z2 Correspondence should be addressed to Jens Pietzsch, j.pietzsch@fzd.de Received 22 September 2008; Accepted 2 April 2009 Recommended by Michel Rigaud The cyclin-dependent kinase (Cdk)-cyclin D/retinoblastoma (pRb)/E2F cascade, which controls the G1/S transition of cell cycle, has been found to be altered in many neoplasias. Inhibition of this pathway by using, for example, selective Cdk4 inhibitors has been suggested to be a promising approach for cancer therapy. We hypothesized that appropriately radiolabeled Cdk4 inhibitors are suitable probes for tumor imaging and may be helpful studying cell proliferation processes in vivo by positron emission tomography. Herein, we report the synthesis and biological, biochemical, and radiopharmacological characterizations of two 124I-labeled small molecule Cdk4 inhibitors (8-cyclopentyl-6-iodo-5-methyl-2-(4-piperazin-1-yl- phenylamino)-8H-pyrido[2,3-d]-pyrimidin-7-one (CKIA) and 8-cyclopentyl-6-iodo-5-methyl-2-(5-(piperazin-1-yl)-pyridin-2- yl-amino)-8H-pyrido[2,3-d]pyrimidin-7-one (CKIB)). Our data demonstrate a defined and specific inhibition of tumor cell proliferati