Methods of cancer detection using parpi-fl

Patent metadata

Field	Value
Publication number	US-2020360538-A1
Application number	US-201916712919-A
Country	US
Kind code	A1
Filing date	Dec 12, 2019
Priority date	Apr 10, 2015
Publication date	Nov 19, 2020
Grant date	—

Abstract

The present disclosure describes methods of use of a composition comprising PARPi-fl to be administered to the oral cavity (e.g., via topical application to surfaces of the oral cavity) followed by imaging of the oral cavity for detection of squamous cell carcinoma of the oral cavity (e.g., in vivo, e.g., in a dental office setting or intraoperatively). The results disclosed herein show that topically applied PARPi-fl and subsequent intraoperative imaging of oral cavities can improve surgical removal of squamous cell carcinoma cells compared to healthy cells.

First claim

What is claimed is:

1 . A method for the non-invasive screening of a subject for oral squamous cell carcinoma (OSCC), the method comprising the steps of:
administering a composition comprising a PARP1 inhibitor conjugated to a fluorophore (PARPi-f) onto and/or into tissue in an oral cavity of the subject; flushing the tissue in the oral cavity of the subject to reduce or remove unbound components of the composition while leaving bound components of the composition; and detecting fluorescence from the fluorophore after the administering and the flushing steps, thereby identifying potential OSCC.

2 . The method of claim 1 , wherein the subject is a human patient.

3 . The method of claim 1 , wherein the method takes place in a dentist office or other nonsurgical setting.

4 . The method of claim 1 , wherein the administering comprises topically administering the composition.

5 . The method of claim 1 , wherein the composition is a liquid composition.

6 . The method of claim 5 , wherein the liquid composition is selected from the group consisting of an oral rinse, a mouthwash, a spray, an intravenous injection, and a local intramuscular injection.

7 . The method of claim 1 , wherein the composition is a gel, paste, or other solid or spray.

8 . The method of claim 1 , wherein the fluorophore comprises a boron-dipyrromethene.

9 . The method of claim 1 , wherein the PARPi-fl has a molecular weight no greater than about 1000 Da.

10 . The method of claim 1 , wherein the fluorophore has a molecular weight no greater than about 500 Da.

11 . The method of claim 1 , wherein the flushing comprises waiting a period of time following the administering step such that the tissue clears unbound components of the composition.

12 . The method of claim 1 , wherein the flushing comprises rinsing and/or gargling.

13 . The method of claim 1 , wherein detecting fluorescence comprises using a fluorescence scanning imaging device.

14 . The method of claim 1 , wherein potential OSCC is identified following exposure of the oral cavity tissue to excitation light.

15 . A method for intraoperative detection of a tumor margin and/or residual tumor tissue during tumor removal surgery, the method comprising the steps of:
administering a composition comprising a PARP1 inhibitor conjugated to a fluorophore (PARPi-fl) onto and/or into a viewable tissue surface of the subject, wherein the viewable tissue surface is viewable during an operative procedure; flushing the viewable tissue surface to reduce or remove unbound components of the composition while leaving bound components of the composition; and detecting fluorescence from the fluorophore after the administering and the flushing steps, thereby identifying the tumor margin and/or residual tumor tissue.

16 . A method of assessing efficacy of a cancer therapy in a subject receiving treatment for an oral carcinoma, the method comprising administering to the subject a PARP1 inhibitor conjugated to a fluorophore (PARPi-fl).

17 . The method of claim 1 , further comprising administering 18 F-PARPi to the subject.

18 . The method of claim 1 , wherein the PARP1 inhibitor is selected from the group consisting of AZD2281, AG014699 (rucaparib), ABT888 (veliparib), BSI201 (iniparib), BSI101, DR2313, FR 247304, GPI15427, GPI16539, M 4827, NU1025, NU1064, NU1085, PD128763, PARP Inhibitor II (INH2BP), PARP Inhibitor m (DPQ), PARP Inhibitor VHI (PJ34), PARP Inhibitor IX (EB-47), and TIQ-A.

19 . The method of claim 11 , wherein the PARP1 inhibitor is selected from the group consisting of AZD2281, AG014699 (rucaparib), ABT888 (veliparib), BSI201 (iniparib), BSI101, DR2313, FR 247304, GPI15427, GPI16539, M 4827, NU1025, NU1064, NU1085, PD128763, PARP Inhibitor II (INH2BP), PARP Inhibitor m (DPQ), PARP Inhibitor VHI (PJ34), PARP Inhibitor IX (EB-47), and TIQ-A.

20 . The method of claim 17 , wherein the method further comprises positron emission tomography of the subject subsequent to administering 18 F-PARPi.

Assignees

• Memorial Sloan Kettering Cancer Center

Inventors

• Kossatz Susanne
• Reiner Thomas
• Weber Wolfgang
• Patel Snehal G

Classifications

• A61K49/0052 Primary

  Small organic molecules (oligomers, polymers, dendrimers A61K49/0054) · CPC title

• A61K9/0014

  Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00) · CPC title

• A61K49/0071

  solution, solute · CPC title

• A61K49/0073

  semi-solid, gel, hydrogel, ointment · CPC title

• A61B5/0036

  including treatment, e.g., using an implantable medical device, ablating, ventilating · CPC title