Intramolecularly-quenched near infrared fluorescent probes
AssigneeThe General Hospital Corporation
InventorsRalph Weissleder, Ching-Hsuan Tung, Umar Mahmood, Lee Josephson, Alexei Bogdanov
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Abstract
An intramolecularly-quenched, near infrared fluorescence probe that emits substantial fluorescence only after interaction with a target tissue (i.e., activation) is disclosed. The probe includes a polymeric backbone and a plurality of near infrared fluorochromes covalently linked to the backbone at fluorescence-quenching interaction-permissive positions separable by enzymatic cleavage at fluorescence activation sites. The probe optionally includes protective chains or fluorochrome spacers, or both. Also disclosed are methods of using the intramolecularly-quenched, near infrared fluorescence probes for in vivo optical imaging.
Claims19
An intramolecularly-quenched fluorescence probe comprising a polymeric backbone and a plurality of near infrared fluorochromes covalently linked to the backbone at fluorescence-quenching interaction-permissive positions separable by enzymatic cleavage at fluorescence activation sites.
An in vivo optical imaging method comprising:
- (a) administering to a living animal or human an intramolecularly-quenched fluorescence probe that accumulates in a target tissue, and comprises a fluorochrome attachment moiety and a plurality of near infrared fluorochromes covalently linked to the fluorochrome attachment moiety at fluorescence-quenching interaction-permissive positions separable by enzymatic cleavage at fluorescence activation sites;
- (b) allowing time for (1) the probe to accumulate in the target tissue, and (2) enzymes in the target tissue to activate the probe by enzymatic cleavage at a fluorescence activation site, if the target tissue is present;
- (c) illuminating the target tissue with near infrared light of a wavelength absorbable by the fluorochromes;
- (d) detecting fluorescence emitted by the fluorochromes, and
- forming an optical image of the target tissue, if present.
An in vivo optical imaging method comprising:
- (a) administering to a living animal or human an intramolecularly-quenched fluorescence probe comprising a fluorochrome attachment moiety and a plurality of near infrared fluorochromes covalently linked to the fluorochrome attachment moiety at fluorescence-quenching interaction-permissive positions separable by enzymatic cleavage at fluorescence activation sites, which enzymatic cleavage occurs in a target tissue;
- (b) allowing time for enzymes in the target tissue to activate the probe by enzymatic cleavage at a fluorescence activation site, if the target tissue is present;
- (c) illuminating the target tissue with near infrared light of a wavelength absorbable by the fluorochromes;
- (d) detecting fluorescence emitted by the fluorochromes, and
- forming an optical image of the target tissue, if present.
Dependencies are inferred from the claim text.