title: New radioiodinated carboxylic and hydroxamic matrix metalloproteinase inhibitor tracers as potential tumor imaging agents.
abstract: Several studies have demonstrated a positive correlation between tumor progression and expression of extracellular proteinases such as matrix metalloproteinases (MMPs). MMP-2 and MMP-9 have become attractive targets for cancer research because of their increased expression in human malignant tumor tissues of various organs, providing a target for medical imaging techniques. Radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4'-[(123)I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid (9) and 2-(4'-[(123)I]iodo-biphenyl-4-sulfonylamino)-3-(1H-indol-3-yl)-propionamide (11) were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives and resulted in radiochemical yields of 60% +/- 5% (n = 3) and 70% +/- 5% (n = 6), respectively. In vitro zymography and enzyme assays showed high inhibition capacities of the inhibitors on gelatinases. In vivo biodistribution showed no long-term accumulation in organs and the possibility to accumulate in the tumor. These results warrant further studies of radioiodinated carboxylic and hydroxamic MMP inhibitor tracers as potential SPECT tumor imaging agents.
authors.affiliation: Department of Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium. ruth.oltenfreiter@rug.ac.be
authors.forename: Ruth
authors.initials: R
authors.lastname: Oltenfreiter
authors.forename: Ludovicus
authors.initials: L
authors.lastname: Staelens
authors.forename: Annabelle
authors.initials: A
authors.lastname: Lejeune
authors.forename: Filip
authors.initials: F
authors.lastname: Dumont
authors.forename: Francis
authors.initials: F
authors.lastname: Frankenne
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Guido
authors.initials: G
authors.lastname: Slegers
mesh_terms: D000577:Amides / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D005240:Feasibility Studies; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D009928:Organ Specificity; D011422:Propionates / Q000737:chemistry / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000577:Amides; D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D061965:Matrix Metalloproteinase Inhibitors; D011422:Propionates; D019275:Radiopharmaceuticals; D020782:Matrix Metalloproteinases; C034666:propionamide