Methods, systems, and associated implantable devices for detecting radiation in patients undergoing treatment for cancer

• US 7,787,937 B2
• Filed: 07/20/2005
• Issued: 08/31/2010
• Est. Priority Date: 09/30/1998
• Status: Expired due to Fees

• Current Assignee: SNC Holdings Corp.
• Original Assignee: Sicel Technologies, Inc., North Carolina State University (University of North Carolina System)
• Inventors: Mueller, Jeffrey, Nagle, H. Troy, Scarantino, Charles W., Hall, Lester C., Kermani, Bahram G.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US11/185,284
• Publication Number:
  US 20050251033A1
• Time in Patent Office: 1,868 Days
• Field of Search: 600/436, 600/302, 128/903, 424/9.2
• US Class Current: 600/436
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/085 combined with means for recording calibration data
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/417 the bone marrow
• CPC Class Codes: A61B 6/507 for determination of haemodynamic parameters, e.g. perfusion CT
• CPC Class Codes: A61N 5/1048 Monitoring, verifying, controlling systems and methods
• CPC Class Codes: A61N 5/1071 for verifying the dose delivered by the treatment plan
• CPC Class Codes: G16H 20/40 relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
• CPC Class Codes: G16H 40/67 for remote operation
• CPC Class Codes: Y10S 128/903 Radio telemetry
• CPC Class Codes: Y10S 128/904 Telephone telemetry
• CPC Class Codes: Y10S 128/92 Computer assisted medical diagnostics

Abstract

Methods and systems for evaluating external beam radiation therapy delivered to a subject include: (a) placing at least one wireless implantable sensor in a first subject at a target location; (b) administering a first dose of radiation therapy into the first subject; (c) obtaining radiation data from the at least one wireless implantable sensor; and (d) calculating a radiation dose amount received by the first subject at the target location based on the radiation data obtained from the at least one wireless sensor during and/or after exposure to the first administered dose of radiation to determine and/or verify a dose amount of radiation delivered to the target location.

Claims

1. A method for monitoring a tumor site of a patient undergoing treatment for cancer, comprising:

administering a radiolabeled agent to the patient subsequent to a chemotherapeutic treatment;

detecting in vivo from at least one wireless implantable sensor configured to reside adjacent solid tissue at a tumor site, a radiation signal in the solid tissue at the tumor site responsive to the administering step;

telemetrically relaying the detected radiation signal to a location external of the patient'"'"'s body;

electronically determining uptake of the radiolabeled agent in the solid tissue based on the relayed detected radiation signal; and

evaluating a patient specific response to the chemotherapeutic treatment and/or a likelihood of clinical efficacy of a subsequent cancer treatment for the patient based on the determined uptake.

2. A method according to claim 1, wherein the radiolabeled agent comprises a radiolabeled chemotherapeutic drug.

3. A method according to claim 2, wherein the relaying step is repeated a plurality of times over a desired time period, wherein the determining step uses the relayed detected radiation signals, and wherein the evaluating step is carried out to electronically provide a likelihood of a favorable or unfavorable patient response to the chemotherapeutic drug based on the determined uptake.

4. A method according to claim 1, wherein the relaying step is repeated a plurality of times over a desired time period, wherein the determining step uses the relayed detected radiation signals, and wherein the evaluating step is carried out to electronically generate a positive or negative predictive treatment outcome based on the determined uptake.

5. A method according to claim 1, wherein the relaying step is repeated a plurality of times over a desired time period, wherein the determining step uses the relayed detected radiation signals proximate in time to the administering step.

6. A method according to claim 1, wherein the evaluating step comprises electronically identifying certain types of treatment as being unlikely to be clinically effective.

7. A method according to claim 1, wherein the telemetrically relaying step comprises inductively powering the sensor, wherein the at least one sensor comprises at least one implantable radiation sensor with a MOSFET-based radiation circuit configured to detect radiation, and wherein the telemetrically relaying step is carried out to relay the radiation signal to a reader.

8. A method according to claim 1, wherein said detecting step is carried out using a plurality of discrete implantable sensors configured to detect radiation using a respective MOSFET-based radiation circuit and the relaying step is configured to telemetrically relay a respective detected radiation signal from each of the plurality of sensors.

9. A method according to claim 1, further comprising detecting a second radiation signal at from a site away from the tumor site using an implantable wireless sensor, and wherein the telemetrically relaying step is carried out to relay both detected radiation signals to a reader.

10. A method according to claim 1, wherein said detecting and relaying steps are carried out to provide a plurality of detected radiation signals for the determining step such that the determining step uses the detected radiation signals obtained at least periodically over a period of time proximate in time to at least one planned subsequent cancer treatment to further identify a favorable treatment time.

11. A detection system for a tumor site, comprising:

at least one wireless chronically implantable radiation sensor configured for in vivo operation, the at least one sensor being configured to detect radiation from a radiolabeled agent administered after a chemotherapeutic treatment in solid tissue proximate a tumor treatment site in the body, wherein the at least one sensor is inductively powered; and

an external reader configured to inductively power and telemetrically communicate with the at least one radiation sensor to wirelessly receive radiation signal data associated with radiation detected by the at least one radiation sensor; and

a processor in the reader or in communication with the reader configured to monitor the received radiation data over time to determine uptake of the radiolabeled agent at the tumor site and to evaluate a patient-specific tumor response to the chemotherapeutic treatment.

12. A system according to claim 11, wherein the at least one sensor is adapted to reside on and/or in a tumor at a depth in the body of a subject.

13. A system according to claim 11, wherein the at least one sensor is a plurality of discrete implantable sensors, each configured to wirelessly transmit signals associated with the in vivo detected radiation to the reader over a plurality of monitoring periods during a treatment regime extending from between about 1 week-3 months.

14. A system according to claim 11, further comprising a second at least one chronically implantable radiation sensor in communication with the external reader, the second at least one sensor configured for in vivo operation to detect radiation from the administered radiolabeled agent in solid tissue at a location which is spaced apart from the tumor treatment site in the body.

15. A computer program product for evaluating a cancer treatment regimen in a cancer patient, said computer program product comprising a computer readable non-transitory medium having computer readable program code embodied therein, the computer readable program code comprising:

computer readable program code for operating at least one wireless sensor to obtain a plurality of radiation signals over time corresponding to radiation in solid tissue at a tumor site responsive to an administration of a radiolabeled material which is administered after a chemotherapeutic treatment;

computer readable program code for determining uptake of the radiolabeled material in the solid tissue at the tumor site using the obtained radiation signals; and

computer readable program code for evaluating at least one of the following based on the determined uptake;

(a) cell proliferation of the tumor site;

(b) a patient specific response to the chemotherapeutic treatment; and

(c) a likelihood of clinical efficacy of a subsequent planned cancer treatment for the patient.

16. A computer program product according to claim 15, wherein the computer readable program code for evaluating is configured to evaluate cell proliferation at the tumor site and provide a prediction of the likelihood of a favorable or unfavorable response to the chemotherapeutic treatment.

17. A detection system for detecting in vivo radiation in a body of an oncology patient, comprising:

at least one wireless radiation sensor configured for in vivo operation, the at least one sensor being configured to detect radiation in solid tissue proximate a tumor treatment site in the body of the oncology patient in response to a radiolabeled agent administered after a chemotherapeutic treatment, wherein the at least one sensor is inductively powered; and

an external reader configured to telemetrically communicate with the at least one radiation sensor, the reader being configured to wirelessly receive radiation signal data associated with radiation detected by the at least one sensor proximate the tumor treatment site over a desired time period; and

a processor in the reader or in communication with the reader and a physician computer, the processor configured to determine uptake of the radiolabeled agent associated with the received radiation signal data and generate at least one of the following based on the determined uptake;

(a) cell proliferation data of the tumor treatment site;

(b) the patient'"'"'s response to the chemotherapeutic treatment; and

(c) a likelihood of clinical efficacy of the chemotherapeutic treatment and/or a subsequent cancer treatment.

18. A system according to claim 17, wherein the at least one radiation sensor is chronically implantable and adapted to reside proximate a tumor treatment site at a depth in the body of a subject, wherein at least one of the at least one radiation sensor is further configured to detect oxygen at the tumor treatment site, and wherein the processor is configured to assess oxygenation of the tumor site based on the detected oxygen.

19. A system according to claim 17, wherein the at least one radiation sensor is a plurality of implantable sensors, with at least one of the implantable sensors detects radiation associated with the administered radiolabeled agent at a spaced apart location from another of the sensors in the patient'"'"'s body.

20. A system according to claim 17, wherein the at least one radiation sensor system is configured to detect at least one additional parameter including at least one of the following:

(i) oxygen level;

(ii) pH; and

(iii) temperature at the tumor treatment site and telemetrically relay the detected additional parameter, and

wherein the processor is configured to provide at least one of the following tumor related parameters to the physician computer based on the detected radiation and/or the additional detected parameter;

(a) cell proliferation status;

(b) hypoxia;

(c) cell kinetics; and

(d) a cell proliferation rate.

21. A system according to claim 17, wherein the processor system is configured to provide cell proliferation data in response to the determined uptake of the radiolabeled agent.

22. A method for monitoring a tumor site of a patient, comprising:

detecting from at least one sensor adjacent or in solid tissue at the tumor site a radiation signal in response to a radiolabeled substance administered after a chemotherapeutic treatment;

relaying the detected radiation signal to a location external of the patient'"'"'s body; and

electronically determining at least one tumor physiologic parameter based on the relayed radiation signal; and

evaluating the patient'"'"'s response to the chemotherapeutic treatment and/or whether to administer a subsequent treatment to the patient based on the determined tumor parameter.

23. A method according to claim 22, further comprising administering a chemotherapeutic treatment to the patient, then administering the radiolabeled substance to the patient proximate in time but before the detecting step.

24. A method according to claim 23, wherein the radiolabeled substance comprises a radio-tagged ligand, wherein the administering is carried out proximate in time to the detecting step, and wherein the determining step determines cell proliferation data and the evaluating step is carried out to assess the patient'"'"'s response to the chemotherapeutic treatment.

25. A method according to claim 22, wherein the radiolabeled substance comprises a radioactive tagged ligand and the method further comprises administering the radioactive tagged ligand to the patient before the detecting step.

26. A system for monitoring a tumor site in an oncology patient, comprising:

at least one wireless implantable radiation sensor configured to be positioned adjacent solid tissue proximate a tumor treatment site, the at least one sensor being configured to detect radiation associated with radiolabeled agent in the solid tissue proximate the tumor treatment site in the body, wherein the radiolabeled agent is administered to the patient after a chemotherapeutic treatment; and

an external reader operably associated with the at least one radiation sensor, the reader being configured to wirelessly receive radiation signal data from the at least one sensor, wherein said reader comprises a processor configured to monitor the detected radiation at the tumor site over time to determine uptake of the radiolabeled agent at the tumor treatment site to assess at least one of the following tumor physiology parameters subsequent to the chemotherapeutic treatment;

(a) cell proliferation status;

(b) cell kinetics; and

(c) a cell proliferation rate.

27. A system according to claim 26, wherein the reader is configured to determine a change in cell proliferation to assess the patient'"'"'s response to the chemotherapeutic treatment.

28. A system according to claim 26, wherein the at least one sensor is a plurality of spaced apart implantable sensors configured to be placed at different positions at the tumor treatment site and/or in the patient'"'"'s body, and wherein the reader is configured to receive signal data from the sensors and determine changes in cell proliferation after the chemotherapeutic treatment.

29. A system for monitoring a tumor site in an oncology patient, comprising:

at least one wireless sensor configured to reside adjacent to and detect a radiation signal and an oxygen signal from cells in solid tissue proximate a tumor treatment site in the body; and

an external reader operably associated with the at least one sensor, the reader being configured to wirelessly receive signal data from the at least one sensor including radiation signal data obtained over a desired time associated with a radiolabeled agent administered to the patient after a chemotherapeutic treatment;

and a processor in the reader or in communication with the reader configured to determine uptake of the radiolabeled agent in the solid tissue at the tumor treatment site using the radiation signal data obtained over time to assess at least one of the following tumor site physiology or biologic parameters after the chemotherapeutic treatment;

(a) cell proliferation status;

(b) cell kinetics; and

(c) a cell proliferation rate.

30. A system according to claim 29, wherein the reader is configured to obtain oxygen signal data from the at least one sensor, and wherein the processor is configured to use the received oxygen signal to assess hypoxia of the tumor site and evaluate a patient specific response to the chemotherapeutic treatment and/or a likelihood of clinical efficacy of a planned subsequent cancer treatment for the patient based on the determined uptake and whether the tumor site has hypoxia.