# US 11,998,765 B2 · Cancer imaging methods and cancer treatment methods using thermotherapy and drug delivery

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- Number: US 11,998,765 B2
- Document ID: US11998765B2
- Status: Granted
- Kind: B2
- Application number: 17/489,655
- Filed: 2021-09-29
- Published: 2022-03-31
- Granted: 2024-06-04
- Earliest claimed: 2020-09-29
- Assignees: Cancer Rx, LLC
- Applicants: Cancer Rx, LLC
- Inventors: Gholam A. Peyman; Michael Kolios; Celina Yang; Jahangir Tavakkoli; Elyas Shaswary; Hisham Assi; Joseph Carl Kumaradas
- Web page: https://patentgrep.com/patent/US11998765B2

## CPC

- A61N 7/02: Localised ultrasound hyperthermia
- A61B 5/01: Measuring temperature of body parts {; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue} (clinical contact thermometers G01K13/20)
- A61B 8/00: Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B 18/18: by applying electromagnetic radiation, e.g. microwaves
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 41/0033: {Sonodynamic cancer therapy with sonochemically active agents or sonosensitizers, having their cytotoxic effects enhanced through application of ultrasounds (ultrasound therapy per se A61N7/00)}
- A61K 41/0042: {Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion}
- A61M 37/0092: {using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis}
- A61N 5/062: {Photodynamic therapy, i.e. excitation of an agent}
- A61N 5/067: using laser light
- A61B 5/0095: {by applying light and detecting acoustic waves, i.e. photoacoustic measurements}
- A61B 18/14: Probes or electrodes therefor
- A61B 2018/00791: {Temperature}
- A61B 2090/378: {using ultrasound}
- A61N 2/002: {in combination with another treatment}
- A61N 5/025: {Warming the body, e.g. hyperthermia treatment}
- A61N 2005/0627: {Dose monitoring systems and methods}
- A61N 2007/0004: {Applications of ultrasound therapy}
- A61N 2007/0082: {Scanning transducers}
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}

## Abstract

Cancer imaging methods and cancer treatment methods using thermotherapy and drug delivery are disclosed herein. In one embodiment, the temperature of heated tissue is determined from radio-frequency data from an ultrasound transducer based upon a change in backscattered energy of acoustic harmonics. In another embodiment, a plurality of nanocarriers containing an anti-tumor medication are administered to a patient, and are excited in a first non-thermal ultrasound mode and/or a second thermal ultrasound mode using an ultrasound source. In yet another embodiment, a plurality of nanoparticles are administered to a patient, then at least some of the nanoparticles are heated along with tissue at a site of a tumor, and a photoacoustic imaging unit is used to determine a temperature of the heated tissue at the site of the tumor.

## Claims

### Claim 1

A cancer treatment method using ultrasound energy for targeted drug delivery, the method comprising the steps of:
administering a plurality of nanocarriers to a patient in need thereof so as to target a tumor in the patient, the administered nanocarriers containing an anti-tumor medication; and
exciting the nanocarriers in a first non-thermal ultrasound mode and/or a second thermal ultrasound mode using an ultrasound source that generates a non-thermal ultrasonic wave and/or a thermal ultrasonic wave so as to release the anti-tumor medication from one or more of the plurality of nanocarriers at a site of the tumor;
wherein the ultrasound source is a therapeutic ultrasound transducer; and
wherein the step of exciting the nanocarriers further comprises exciting the nanocarriers using the therapeutic ultrasound transducer in the first non-thermal ultrasound mode, the therapeutic ultrasound transducer emitting pulsed high intensity focused ultrasound (pHIFU) for mechanical excitation of the plurality of nanocarriers in the first non-thermal ultrasound mode so as to release the anti-tumor medication from the nanocarriers by rupturing membranes of the nanocarriers and/or peeling a polymer coating off the nanocarriers.

### Claim 2 (depends on 1)

The cancer treatment method according to claim 1, wherein the plurality of nanocarriers are selected from the group consisting of antibody-conjugated nanoparticles, aptamer-conjugated nanoparticles, liposomes, and micelles.

### Claim 3 (depends on 1)

The cancer treatment method according to claim 1, wherein at least some of the plurality of nanocarriers are conjugated with cell penetrating peptides (CPPs).

### Claim 4 (depends on 1)

The cancer treatment method according to claim 1, wherein the therapeutic ultrasound transducer has a frequency of approximately 1 megaHertz.

### Claim 5 (depends on 4)

The cancer treatment method according to claim 4, wherein the step of exciting the nanocarriers with the pulsed high intensity focused ultrasound (pHIFU) in the first non-thermal ultrasound mode further comprises generating approximately 25 millisecond pulses at a pulse repetition frequency of approximately 1 Hertz with a focal peak pressure of approximately 3.3 megapascals for a total exposure time duration of approximately 30 seconds.

### Claim 6 (depends on 5)

The cancer treatment method according to claim 5, wherein, in the first non-thermal ultrasound mode where the therapeutic ultrasound transducer is emitting the pulsed high intensity focused ultrasound (pHIFU), the therapeutic ultrasound transducer has an acoustic power of approximately 332 watts and an input voltage of approximately 500 mVpp.

### Claim 7 (depends on 4)

The cancer treatment method according to claim 4, wherein the step of exciting the nanocarriers further comprises exciting the nanocarriers using the therapeutic ultrasound transducer in the second thermal ultrasound mode, the therapeutic ultrasound transducer emitting low intensity focused ultrasound (LIFU) for thermal heating of the plurality of nanocarriers in the second thermal ultrasound mode so as to release the anti-tumor medication from the nanocarriers by thermally rupturing the nanocarriers and/or melting a polymer coating of the nanocarriers.

### Claim 8 (depends on 7)

The cancer treatment method according to claim 7, wherein the step of exciting the nanocarriers with the low intensity focused ultrasound (LIFU) in the second thermal ultrasound mode further comprises generating a thermal ultrasonic wave with the frequency of approximately 1 megaHertz at a focal peak pressure of approximately 0.35 megapascals and a 50% duty cycle for a total exposure time duration of approximately 5 minutes.

### Claim 9 (depends on 8)

The cancer treatment method according to claim 8, wherein, in the second thermal ultrasound mode where the therapeutic ultrasound transducer is emitting the low intensity focused ultrasound (LIFU), the therapeutic ultrasound transducer has an acoustic power of approximately 2.1 watts and an input voltage of approximately 160 mVpp.

### Claim 10 (depends on 8)

The cancer treatment method according to claim 8, wherein, in the second thermal ultrasound mode where the therapeutic ultrasound transducer is emitting the low intensity focused ultrasound (LIFU), the therapeutic ultrasound transducer thermally heats the plurality of nanocarriers to a temperature in a range between about 37° C. and about 47° C. under feedback control of the therapeutic ultrasound transducer by a feedback controller.

### Claim 11 (depends on 1)

The cancer treatment method according to claim 1, wherein the anti-tumor medication comprises doxorubicin.