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US 2018/0000973 A1Published application
Agents for use in the detection of nuclease activity
OwnerFrank J. HERNÁNDEZ HINCAPIÉ, Luiza Iuliana HERNANDEZinventors
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OwnerFrank J. HERNÁNDEZ HINCAPIÉ, Luiza Iuliana HERNANDEZinventors
Estimating the term…
The present invention relates to the field of diagnostics and, more in particular, to MRI activatable contrast agents and compositions thereof for the detection of nuclease activity, wherein said nuclease activity is caused by microbial infection or by nuclease activity related to cancer, particularly colon cancer or pancreatic cancer. Activatable contrast agents for MRI have been developed, wherein the oligonucleotide is flanked by a paramagnetic and a superparamagnetic agent, and thus providing magnetic quenching. Moreover, the oligonucleotide has regions that confer resistance to mammalian endonucleases and sensitivity to microbial endonucleases. When the activatable contrast agent of the invention is in the presence of microbial nuclease activity or a tumour cell nuclease activity, the oligonucleotide is cleaved, agents are unquenched, and the signal derived from the activated contrast agent is detected by MRI.
An activatable contrast agent for magnetic resonance imaging (MRI) comprising:
The contrast agent according to the preceding claim, wherein the chemically modified nucleotides are comprised by the region of the oligonucleotide conferring resistance to mammalian endonucleases.
The contrast agent according to any of the preceding claims, wherein the region comprising a nucleotide sequence conferring sensitivity to a microbial nuclease but not to mammalian endonucleases comprises a nucleotide sequence selected from the group consisting of TT, AA, TA and AT.
The contrast agent according to any of the preceding claims, wherein the quenching between the superparamagnetic agent in (i) and the at least one paramagnetic agent in (ii) is achieved by a length of the oligonucleotide in (iii) of at least 2 nucleotides and/or by the presence of a nucleotide sequence in the oligonucleotide in (iii) having a secondary structure.
The contrast agent according to any of the preceding claims, wherein said at least one oligonucleotide comprises the sequence:
The contrast agent according to any of the preceding claims, wherein the paramagnetic agent is selected from the group consisting of a gadolinium-based agent and a manganese-based agent, and/or wherein the superparamagnetic agent comprises iron oxide or iron platinum.
The contrast agent according to the preceding claim, wherein the gadolinium-based agent is selected from the group consisting of gadolinium-DTPA, gadolinium-DOTA, gadolinium-NOTA, gadolinium-DOTRA, and wherein the manganese-based agent is manganese-DPDP.
The method according to the preceding claim, wherein the nuclease activity in the sample is a microbial nuclease activity or a tumor cell nuclease activity.
Dependencies are inferred from the claim text.