The present application claims priority to Provisional Application No. 60/989,629, filed Nov. 21, 2007, the entire contents of which are incorporated herein by reference, including any references cited therein.
FIELD OF THE INVENTION
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The present invention relates to an apparatus and methods for the non-invasive diagnosis and/or treatment of diseased tissue. In particular, the present invention relates to an apparatus and related methods for the non-invasive diagnosis and/or treatment of tumors and metastatic cancer with High Intensity Focused Ultrasound (HIFU).
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Diseased tissue, such as a cancerous tumor, is commonly diagnosed by taking a biopsy of the tissue for pathology. The biopsy procedure, however, is invasive and involves the removal of a portion of the tissue for analysis. Clearly, it is much more desirable to have a non-invasive method for such diagnosis.
One approach to the treatment of diseased tissue, particularly tumors, is surgical removal. Surgical removal, however, is invasive and can be quite complex and time consuming. Additionally, surgical treatment requires the selective treatment of each individual diseased tissue. Surgical treatment can also result in serious complications, such as from anesthesia. Clearly, a more comprehensive and non-invasive treatment of similar or better efficacy than surgical removal is desirable.
High Intensity Focused Ultrasound (HIFU) has been demonstrated to be a safe modality to treat diseased tissue noninvasively. For example, HIFU has been used to treat prostrate cancer, kidney cancer, and testicular cancer. An exemplary system used to administer HIFU is the Sonablate® 500 (SB500) system available from Focus Surgery, located at 3940 Pendleton Way, Indianapolis, Ind. 46226.
Further exemplary embodiments of systems used to administer HIFU are disclosed in U.S. Patent Publication No. US2007/0010805, filed Jul. 8, 2006, titled “Method and Apparatus for Treatment of Tissue;” U.S. Patent Application Publication No. US 2005/0240127, filed Mar. 2, 2005, titled “Ultrasound Phased Arrays;” U.S. Provisional Patent Application Publication No. US2008/0091123, filed May 6, 2004, titled “Treatment of Spatially Oriented Disease with a Single Therapy, Imaging, and Doppler Ultrasound Transducer;” PCT Patent Application Serial No. US2005/015648, filed May 5, 2005, designating the US, titled “Method and Apparatus for the Selective Treatment of Tissue;” U.S. Pat. No. 4,084,582; U.S. Pat. No. 4,207,901; U.S. Pat. No. 4,223,560; U.S. Pat. No. 4,227,417; U.S. Pat. No. 4,248,090; U.S. Pat. No. 4,257,271; U.S. Pat. No. 4,317,370; U.S. Pat. No. 4,325,381; U.S. Pat. No. 4,586,512; U.S. Pat. No. 4,620,546; U.S. Pat. No. 4,658,828; U.S. Pat. No. 4,664,121; U.S. Pat. No. 4,858,613; U.S. Pat. No. 4,951,653; U.S. Pat. No. 4,955,365; U.S. Pat. No. 5,036,855; U.S. Pat. No. 5,054,470; U.S. Pat. No. 5,080,102; U.S. Pat. No. 5,117,832; U.S. Pat. No. 5,149,319; U.S. Pat. No. 5,215,680; U.S. Pat. No. 5,219,401; U.S. Pat. No. 5,247,935; U.S. Pat. No. 5,295,484; U.S. Pat. No. 5,316,000; U.S. Pat. No. 5,391,197; U.S. Pat. No. 5,409,006; U.S. Pat. No. 5,443,069, U.S. Pat. No. 5,470,350, U.S. Pat. No. 5,492,126; U.S. Pat. No. 5,573,497, U.S. Pat. No. 5,601,526; U.S. Pat. No. 5,620,479; U.S. Pat. No. 5,630,837; U.S. Pat. No. 5,643,179; U.S. Pat. No. 5,676,692; U.S. Pat. No. 5,840,031; U.S. Pat. No. 5,762,066; U.S. Pat. No. 6,685,640; U.S. Abandoned patent application Ser. No. 07/840,502 filed Feb. 21, 1992; Australian Patent No. 5,732,801; Canadian Patent No. 1,332,441; and Canadian Patent No. 2,250,081 (collectively the “HIFU patents”), the disclosures of all of which are expressly incorporated herein by reference in their entireties.
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OF THE INVENTION
The present invention provides a method for diagnosing the presence of a tumor in a patient. The tumor is subjected to HIFU to cause the tumor cells to release cellular material. The cellular material comprises at least one tumor marker. Biological fluid obtained from the patient is then evaluated to determine the presence and/or level of the tumor marker in the fluid. Preferably, the biological fluid is blood, urine or saliva.
The invention also provides a method of treating a malignant tumor in a patient. HIFU is delivered to the tumor to cause the tumor cells to release cellular material that provokes an immune response. In one embodiment, the patient's immune response to the tumor cells is amplified by using one or more immunotherapy techniques.
In an alternative embodiment, the invention provides a method of treating metastatic cancer in a patient, where the cancer arises from at least one malignant tumor in the patent. HIFU is delivered to the tumor, and the HIFU causes the release of cellular material from tumor cells within the tumor, thus provoking an immune response that encompasses some or all of the metastatic cells. In one embodiment, the patient's immune response to the tumor cells is stimulated by using one or more immunotherapy techniques.
In yet another alternative embodiment, the invention provides a method for treating tumors that are not agitated by HIFU treatment. HIFU is delivered to a tumor, wherein the HIFU causes the release of cellular material that provokes an immune response to treat the unagitated tumors.
However, persons skilled in the art will be able to apply the apparatus and methods of the invention to human patients and to non-human mammals, such as laboratory mice and rats, dogs, cats, horses, and primates, for research, diagnostic, or treatment purposes.
Additional features of the present invention will become apparent to those skilled in the art upon consideration of the following detailed description of the illustrative embodiments exemplifying the best mode of carrying out the invention as presently perceived.
As used herein, the term “tumor marker” is any detectable molecule from a tumor in a mammal that indicates the presence of the tumor in the mammal.
BRIEF DESCRIPTION OF THE DRAWINGS
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The detailed description of the drawings particularly refers to the accompanying figures in which:
FIG. 1 is schematic view of an exemplary HIFU System.
FIG. 2 is an exemplary method of diagnosing diseased tissue with the application of a treatment to agitate or ablate a suspected region of tissue where an example of a system to apply the treatment is the HIFU System of FIG. 1.
FIG. 3 is an exemplary method of treating a tumor with HIFU and immunotherapy.
FIG. 4 is another exemplary method of treating a tumor with HIFU and immunotherapy.
FIG. 5 is a representation of the developed HIFU driving system to drive the LO-HIFU and HI-HIFU.
FIG. 6 shows acoustic probes capable of delivering LO-HIFU and HI-HIFU.
FIG. 7 shows the Total Acoustic Power (TAP) probe output for the acoustic probes when coupled to the developed driving electronics.
FIG. 8 shows the typical in-vitro result using the HI-HIFU and LO-HIFU probe.
FIG. 9 shows the instrument setup for the HIFU treatment of palpable flank tumors.
FIG. 10 shows the instrument setup for the HIFU treatment of footpad tumors.
FIG. 11 shows levels of HSP70 in serum and tumor lysate after HIFU treatment.
FIG. 12 shows the frequency of IFN-γ releasing cells in spleenocytes three days after HIFU treatment.
FIG. 13 shows tumor specific T cell response detected by IFN-γ release assay after HIFU treatment.
FIG. 14 shows cytotoxic function of tumor reactive T cells detected by CD107a mobilization assay after HIFU treatment.