Protease-activated contrast agents for in vivo imaging
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsMatthew S. BOGYO, Martijn VERDOES, Leslie OFORI, Nimali P. WITHANA
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Abstract
Compounds useful as contrast agents in image-guided surgery are provided. The compounds comprise a latent cationic lysosomotropic fragment that is detectable upon cleavage by lysosomal proteases within treated tissues, particularly within tumors and other diseased tissues. Also provided are compositions comprising the compounds and methods for using the compounds, for example in dynamically monitoring protease activity in vivo during image-guided tumor resection surgery.
Claims35
A compound having the formula (I)
- wherein D is a detectable element comprising a fluorescent label;
- Q is a quencher;
- L0 and L1 are linkers;
- AA2 is an amino acid side chain;
- U is O, N, or S;
- R is alkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heteroaralkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, or a protecting group, and is optionally substituted with 1 to 3 A groups;
- and
- each A is independently alkyl, alkenyl, alkynyl, alkoxy, alkanoyl, alkylamino, aryl, aryloxy, arylamino, aralkyl, aralkoxy, aralkanoyl, aralkamino, heteroaryl, heteroaryloxy, heteroarylamino, heteroaralkyl, heteroaralkoxy, heteroaralkanoyl, heteroaralkamino, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkoxy, cycloalkanoyl, cycloalkamino, heterocyclyl, heterocyclyloxy, heterocyclylamino, heterocyclylalkyl, heterocyclylalkoxy, heterocyclylalkanoyl, heterocyclylalkamino, hydroxyl, thio, amino, alkanoylamino, aroylamino, aralkanoylamino, alkylcarboxy, carbonate, carbamate, guanidinyl, urea, halo, trihalomethyl, cyano, nitro, phosphoryl, sulfonyl, sulfonamido, or azido.
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A compound having the formula (III):
- wherein
- D is a detectable element;
- L0 is a linker;
- and
- T is a protease targeting element, optionally comprising a quencher;
- provided that L0 does not comprise an ethoxyethoxy spacer.
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Dependencies are inferred from the claim text.