Claims for Patent: 10,285,759

Summary for Patent: 10,285,759

Title:	Methods and system for image guided cell ablation with microscopic resolution
Abstract:	The invention provides systems and method for the removal of diseased cells during surgery.
Inventor(s):	Lee W. David, Ferrer Jorge
Assignee:	Lumicell, Inc.
Application Number:	US15721247
Patent Claims:	1. An in vivo method of treating a subject with a tumor comprising:(a) administering a composition comprising a molecular imaging probe to the subject, wherein the imaging probe labels tumor cells and/or tumor associated cells;(b) permitting the molecular imaging probe to clear preferentially from healthy tissue leaving the tumor cells and/or tumor associated cells labeled;(c) performing initial resection surgery to remove tumor cells from the subject thereby creating a resection bed;(d) directing light towards the resection bed to excite the molecular imaging probe;(e) obtaining an in situ fluorescence image of the resection bed using an imaging system;(f) detecting the labeled tumor cells and/or the labeled tumor associated cells, if present in the resection bed, using the fluorescence image; and(g) if labeled tumor cells and/or labeled tumor associated cells are detected in (f), performing further resection surgery to remove the labeled tumor cells and/or labeled tumor associated cells.2. The method of claim 1 , wherein detecting the labeled tumor cells and/or the labeled tumor associated cells claim 1 , if present in the resection bed claim 1 , comprises detecting the labeled tumor associated cells claim 1 , if present in the resection bed.3. The method of claim 1 , wherein detecting the labeled tumor cells and/or the labeled tumor associated cells claim 1 , if present in the resection bed claim 1 , comprises detecting both the labeled tumor cells and the labeled tumor associated cells claim 1 , if present in the resection bed.4. The method of claim 1 , wherein the tumor associated cells include tumor associated inflammation cells and/or tumor associated macrophages.5. The method of claim 1 , wherein the light has a wavelength between 100 nm and 2500 nm.6. The method of claim 1 , wherein the molecular imaging probe is a clearance differential probe including a fluorescent label attached to a pharmacokinetic modifier that results in the molecular imaging probe clearing preferentially from the healthy tissue leaving the tumor cells and/or tumor associated cells labeled.7. The method of claim 6 , wherein the fluorescent label has optical properties in the visible spectrum of 350 nm to 670 nm.8. The method of claim 6 , wherein the pharmacokinetic modifier has a molecular weight of between 20 claim 6 ,000 g/mol and 40 claim 6 ,000 g/mol.9. The method of claim 6 , wherein the pharmacokinetic modifier is selected from the group consisting of polyethylene glycol (PEG) claim 6 , dextran claim 6 , polyethylene oxide (PEO) claim 6 , polyoxyethylene (POE) claim 6 , methoxypolyethylene glycol (MPEG) claim 6 , methoxypolypropylene glycol claim 6 , polyethylene glycol-diacid claim 6 , polyethylene glycol monoamine claim 6 , MPEG monoamine claim 6 , MPEG hydrazide claim 6 , MPEG imidazole claim 6 , copolymers of polyethylene glycol and monoxypolypropylene glycol claim 6 , branched polypropylene glycol claim 6 , polypropylene glycol claim 6 , and polylacic-polyglycolic acid.10. The method of claim 6 , wherein the molecular imaging probe comprises a polyethylene glycol (PEG) having a molecular weight of between 20 claim 6 ,000 g/mol and 40 claim 6 ,000 g/mol.11. The method of claim 6 , wherein the fluorescent label is selected from the group consisting of Cy3 claim 6 , Cy3.5 claim 6 , Cy5 claim 6 , Alexa 568 claim 6 , Alexa 546 claim 6 , Alexa 610 claim 6 , Alexa 647 claim 6 , ROX claim 6 , TAMRA claim 6 , Bodipy 576 claim 6 , Bodipy 581 claim 6 , Bodipy TR claim 6 , Bodipy 630 claim 6 , VivoTag 645 claim 6 , and Texas Red.12. The method of claim 1 , wherein the imaging system images the tumor bed with single-cell resolution.13. The method of claim 1 , wherein the composition is administered systemically to the subject.14. The method of claim 1 , wherein the composition is applied to a tissue surface of the subject.15. The method of claim 1 , wherein the molecular imaging probe is imaged at between 12 and 36 hours after administration.16. The method of claim 1 , wherein the image allows for selective detection of the labeled tumor cells and/or labeled tumor associated cells within about 1 cm from the surface of the tissue resection bed and excludes deep tissue emission.17. The method of claim 1 , wherein the subject is a mammal.18. The method of claim 17 , wherein the subject is a human.19. The method of claim 1 , wherein the molecular imaging probe clears preferentially from healthy tissue leaving both tumor cells and tumor associated cells labeled.20. The method of claim 1 , wherein the imaging system comprises: (a) a light source that directs the light towards the resection bed; (b) an optical receptor configured to receive light from the resection bed and obtain the in situ fluorescence image; and (c) an image processor that receives the fluorescence image from the optical receptor and detects the labeled tumor cells and/or the labeled tumor associated cells if present in the resection bed.21. The method of claim 20 , wherein the image processor comprises a field of view (FOV) greater than a diameter of a cell of the resection bed and an analysis resolution matched to the diameter of a cell of the resection bed and configured to receive and analyze light corresponding to each cell in the FOV.22. The method of claim 20 , wherein the light directed by the light source towards the resection bed excites the molecular imaging probe such that the probe emits light.23. The method of claim 20 , wherein the optical receptor comprises at least one selected from a charge-coupled device (CCD) claim 20 , an avalanche photodiode (APD) claim 20 , and a complementary metal-oxide semiconductor (CMOS).24. The method of claim 20 , wherein the optical receptor comprises an array of pixels with an analysis resolution substantially equal to a diameter of the tumor cells and/or tumor associated cells.25. The method of claim 20 , wherein the imaging system locates the labeled tumor cells and/or the labeled tumor associated cells.26. The method of claim 25 , wherein the image processor outputs camera pixel locations of the labeled tumor cells and/or the labeled tumor associated cells.27. The method of claim 20 , wherein the image processor detects the labeled tumor cells and/or the labeled tumor associated cells claim 20 , if present in the resection bed claim 20 , by comparing a fluorescence at each location in the image with a fluorescence threshold.