| 摘要 |
MRI and optical imaging agents that allow for the sensitive detection of a specific bioactivity within a tissue are claimed. These agents are prodrug contrast agents that are bio-activated in vivo in the presence of the specific bioactivity. Also claimed are pharmaceutical compositions comprising these agents and methods of using the agents and compositions comprising the agents. The prodrugs have the following structure: IEM-[(PBM)m-[(MS)n-(MM)o]p]q IEM comprised of a complex between at least one physiologically compatible cyclic or acyclic organic chelating agent, and one of metal ions with atomic numbers 13, 21-34, 39-42, 44-50 or 57-83 and said IEM has one or two open coordination sites before and after bioactivation. PBM are selected from the group consisting of drugs, lipophilic and amphiphilic organic molecules, porphyrins, receptor ligands, steroids, lipids, hormones, peptides, proteins, oligonucleotides and antibodies, whereby the prodrug contrast comprises at least 2 PBMs. MS is a phosphorus-oxygen bond or a amide bond capable of being hydrolysed in vivo by a phosphatase or a serine protease enzyme respectively. MM is selected from charged groups consisting of hydroxyl, amine, ammonium, quaternary amine, amino acid, sulfoxide, phosphate, sulphate, carboxylate, carbohydrate, sugar and metal chelate. The structures of the claimed prodrugs are shown, wherein R is an aliphatic or activated ester.
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