title: Benzamides as melanotropic carriers for radioisotopes, metals, cytotoxic agents and as enzyme inhibitors.
abstract: Benzamide derivatives are known as antipsychotic and antiemetic drugs. Owing to its neurotropic characteristic this class of compounds was found useful for imaging melanoma and melanoma metastases. [(123I)]BZA (N-(2-diethylaminoethyl)-4-[(123I)]iodobenzamide) was the first example which was clinically applied as an imaging agent demonstrating high tumor uptake. This finding initiated research efforts to further improve the affinity and pharmacological properties of this agent. In order to optimize the use of these molecules with respect to costs and wide spread distribution, (99m)Tc labeled benzamides have been developed. Indeed, several (99m)Tc complexes were found suitable for melanoma imaging; however, they were less eligible than radioiodinated benzamides. Besides their use as radiotracers benzamides have been evaluated for magnetic resonance imaging. Molecular imaging with paramagnetic metal contrast agents for magnetic resonance tomography (MRT) is hampered by the inferior sensitivity of MRT. Biochemical trapping was thought to overcome this problem using the polyamine transporter of melanoma cells. One of the neutral, DTPA based Gd complexes comprising 2-(diethylamino)ethylamine and bis-(2-aminoethyl)amine in the side chain led to intracellular uptake values well above the MRI detection limit. An overview about benzamides used for molecular imaging and as transporters for cytostatic agents as well as inhibitors for histone deacetylases concludes this review, demonstrating that benzamide derivatives represent a versatile class of compounds leading to novel imaging and therapeutic agents.
authors.affiliation: Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Oltmanns
authors.forename: M
authors.initials: M
authors.lastname: Eisenhut
authors.forename: W
authors.initials: W
authors.lastname: Mier
authors.forename: U
authors.initials: U
authors.lastname: Haberkorn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005682:Gadolinium; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007457:Iodine Radioisotopes; D008279:Magnetic Resonance Imaging; D008545:Melanoma / Q000000981:diagnostic imaging*; D008670:Metals / Q000737:chemistry; D015394:Molecular Structure; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000494:pharmacology*; D013667:Technetium
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004337:Drug Carriers; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007457:Iodine Radioisotopes; D008670:Metals; D019275:Radiopharmaceuticals; D013667:Technetium; D005682:Gadolinium