TY - JOUR
T1 - Radiolabeled Selective Matrix Metalloproteinase 13 (MMP-13) Inhibitors
T2 - (Radio)Syntheses and in Vitro and First in Vivo Evaluation
AU - Hugenberg, Verena
AU - Wagner, Stefan
AU - Kopka, Klaus
AU - Schäfers, Michael
AU - Schuit, Robert C.
AU - Windhorst, Albert D.
AU - Hermann, Sven
PY - 2017/1/12
Y1 - 2017/1/12
N2 - The noninvasive imaging of MMP activity in vivo could have a high impact in basic research as well as in clinical applications. This approach can be established using radiolabeled MMP inhibitors (MMPIs) as tracers for the detection of activated MMPs by means of PET. However, the complexity of diseases associated with dysregulated MMP expression necessitates the imaging of distinct MMPs or MMP subgroups to distinguish their individual role in specific diseases. To this end, selective and potent MMP-13 inhibitors based on a N,N′-bis(benzyl)pyrimidine-4,6-dicarboxamide core have been synthesized and successfully radiolabeled with carbon-11, fluorine-18, and gallium-68. Selected radiolabeled candidates were evaluated in vitro and in vivo regarding their pharmacokinetic properties and metabolic stability.
AB - The noninvasive imaging of MMP activity in vivo could have a high impact in basic research as well as in clinical applications. This approach can be established using radiolabeled MMP inhibitors (MMPIs) as tracers for the detection of activated MMPs by means of PET. However, the complexity of diseases associated with dysregulated MMP expression necessitates the imaging of distinct MMPs or MMP subgroups to distinguish their individual role in specific diseases. To this end, selective and potent MMP-13 inhibitors based on a N,N′-bis(benzyl)pyrimidine-4,6-dicarboxamide core have been synthesized and successfully radiolabeled with carbon-11, fluorine-18, and gallium-68. Selected radiolabeled candidates were evaluated in vitro and in vivo regarding their pharmacokinetic properties and metabolic stability.
UR - http://www.scopus.com/inward/record.url?scp=85018193434&partnerID=8YFLogxK
U2 - https://doi.org/10.1021/acs.jmedchem.6b01284
DO - https://doi.org/10.1021/acs.jmedchem.6b01284
M3 - Article
C2 - 27981835
SN - 0022-2623
VL - 60
SP - 307
EP - 321
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 1
ER -