Methods, systems, and associated implantable devices for dynamic monitoring of physiological and biological properties of tumors

• US 6,963,770 B2
• Filed: 04/24/2003
• Issued: 11/08/2005
• Est. Priority Date: 09/30/1998
• Status: Expired due to Term

• 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.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US10/422,120
• Publication Number:
  US 20030195396A1
• Time in Patent Office: 929 Days
• Field of Search: 600/436, 600/302, 128/903
• 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 of monitoring and evaluating the status of a tumor undergoing treatment includes monitoring in vivo at least one physiological parameter associated with a tumor in a subject undergoing treatment, transmitting data from an in situ located sensor to a receiver external of the subject, analyzing the transmitted data, repeating the monitoring and transmitting steps at sequential points in time and evaluating a treatment strategy. The method provides dynamic tracking of the monitored parameters over time. The method can also include identifying in a substantially real time manner when conditions are favorable for treatment and when conditions are unfavorable for treatment and can verify or quantify how much of a known drug dose or radiation dose was actually received at the tumor. The method can include remote transmission from a non-clinical site to allow oversight of the tumor'"'"'s condition even during non-active treatment periods (in between active treatments). The disclosure also includes monitoring systems with in situ in vivo biocompatible sensors and telemetry based operations and related computer program products.

Claims

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

positioning at least one wireless sensor in tissue in a region of interest in the body of a patient being treated for cancer;

administering a therapeutic radiolabeled analyte to the patient;

detecting in vivo from the at least one sensor a signal corresponding to radiation in the region of interest in the patient responsive to the administering step;

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

monitoring the signal over time to determine the localized response of the patient to the administered analyte to provide patient-specific response data that can be used to develop a patient specific cancer treatment strategy and/or evaluate the clinical efficacy of the treatment in the patient.

2. A method according to claim 1, wherein the therapeutic radiolabeled analyte is a beta labeled analyte.

3. A method according to claim 2, further comprising determining drug uptake and/or utilization based on the monitored signal response data.

4. A method according to claim 2, further comprising evaluating blood flow proximate to, on and/or in a tumor in the localized region based on said monitored signal response data.

5. A method according to claim 2, further comprising evaluating the patient'"'"'s sensitivity to at least one selected cancer therapeutic drug based on said monitored signal response data.

6. A method according to claim 2, further comprising determining drug distribution in a localized region in the patient based on said monitored signal response data.

7. A method according to claim 2, wherein the localized region is a cancerous tumor, and wherein said method further comprises determining cancer cell sensitivity or receptiveness to a predetermined therapeutic drug treatment in the tumor.

8. A method according to claim 2, wherein the patient is a human subject, and wherein the localized region comprises a tumor treatment site, said method further comprising determining a dose of radiation delivered to the tumor treatment site by the radiolabeled analyte based on said monitoring step.

9. A method according to claim 2, wherein said sensor is positioned spatially proximate to a tumor in the patient, and wherein said administering step is first carried out at a time which is proximate to a first planned therapeutic treatment, and wherein said detecting step further comprises determining if the tumor is likely to be responsive to the planned treatment based on said detecting and monitoring steps.

10. A method according to claim 2, further comprising selecting a pharmaceutical therapeutic treatment drug based on said monitoring step.

11. A method according to claim 1, further comprising evaluating cell proliferation proximate to and/or in a tumor treatment site based on said monitored signal response data.

12. A method according to claim 1, further comprising generating a predictive treatment outcome based on the monitored response data.

13. A method according to claim 1, wherein the monitoring step is carried out in substantially real time.

14. A method according to claim 1, further comprising excluding certain types of treatment as being unlikely to be clinically effective based on the response data obtained by said monitoring step.

15. A method according to claim 1, wherein the step of positioning is carried out so that at least one sensor is positioned in the body such that it resides proximate to, on and/or in a cancerous tumor.

16. A method according to claim 15, wherein the step of positioning is carried out so that the sensor is chronically implanted in the subject.

17. A method according to claim 16, wherein the sensor is a unitary body implantable sensor configured to detect radiation in at least one of a direct or indirect mode of detection and wirelessly communicate the detected radiation data to an externally located reader.

18. A method according to claim 15, wherein the sensor includes a sensor probe body connected to and spaced apart from a processor body, and wherein the step of positioning comprises implanting the sensor probe body at a first location proximate to or in the tumor site so that it can detect radiation in a direct and/or indirect radiation detection mode and implanting the processor body at a second subcutaneous location proximate normal tissue, the second location being spaced apart from the first location.

19. A method according to claim 1, wherein said at least one sensor is a plurality of sensors configured to detect the emitted radiation from the radiolabeled analyte at a plurality of different locations in vivo within the region of interest.

20. A method according to claim 19, wherein the step of positioning is carried out so that at least one sensor is positioned proximate to cancerous tissue and another sensor is positioned proximate to normal tissue, and wherein said detecting step detects the radiation corresponding to the sensors located proximate to both normal and cancerous tissue.

21. A method according to claim 1, wherein said monitoring step determines cell sensitivity or receptiveness to uptake and/or retention of at least one of a selected group of chemotherapeutic agents.

22. A method according to claim 1, wherein said monitoring step is carried out such that the radiation in the region of interest is monitored at least periodically over a period of time extending for at least between about 0.25-48 hours proximate in time to each of a plurality of planned and/or delivered therapeutic treatments.

23. A method according to claim 22, wherein said administering step is carried out proximate in time to a planned therapeutic treatment, and wherein based on said detecting and monitoring steps, a clinician selects at least one of (a) a suitable chemotherapy treatment and (b) a treatment time.

24. A detection system for detecting radiation emitted from an internally administered radiolabeled analyte, comprising:

at least one wireless implanted radiation sensor contigtzred for in vivo operation, the at least one sensor being configured to directly and/or indirectly detect beta radiation from an internally administered beta radiolabeled analyte proximate to a targeted cancer treatment site in the body, wherein the at least one sensor is configured to detect, at least intermittently, over a period of desired time; and

an external reader operably associated with the at least one radiation sensor and configured to receive signal data associated with the direct and/or indirectly detected radiation from the at least one sensor, wherein said system is configured to dynamically monitor selected in vivo parameters associated with one or more of the dose, uptake and/or processing of the radiation from the internally administered radiolabeled analyte at the targeted cancer treatment site.

25. A system according to claim 24, wherein the sensor is configured as a chronically implanted sensor configured for at least one of direct or indirect detection of radiation and adapted to reside on and/or in a tumor at any depth in the body of a subject.

26. A system according to claim 24, wherein the at least one sensor is configured to wirelessly transmit signals associated with the in vivo detected radiation over a plurality of monitoring periods during a treatment regime extending from between about 1 week-3 months.

27. A system according to claim 24, wherein the internally administered radiolabeled analyte comprises a therapeutic radiolabled analyte, wherein the at least one sensor is configured to detect radiation from the therapeutic radiolabled analyte and wirelessly transmit signals associated with the in vivo detected radiation at desired spaced apart monitoring intervals corresponding to a plurality of different treatment sessions that are delivered over at least about a one month time period.

28. A system according to claim 24, wherein the at least one sensor is a plurality of sensors, including first and second sensors that are adapted to detect radiation emitted from respective first and second spatially separate locations in the target treatment site.

29. A system according to claim 24, wherein the at least one sensor is a plurality of sensors configured to be individually operable.

30. A system according to claim 29, wherein the plurality of sensors includes a first sensor adapted to be held at a first location associated with normal or non-diseased tissue, and a second sensor adapted to be held at a second location associated with excised, diseased, abnormal, and/or cancerous tissue.

31. A computer program product for evaluating radiation dose received at a target treatment site from a radiolabeled analyte administered in response to a cancer treatment regimen, said computer program product comprising:

computer readable program code for receiving a plurality of measurements of radiation detected in vivo in tissue from a chronically implanted sensor located about a local targeted cancer treatment site in the body of a human subject undergoing treatment for cancer, the detected radiation corresponding to radiation emitted from a selected beta radiolabeled analyte administered internally to the subject; and

computer readable program code for computing one or more of a patient specific in vivo radiation dose, uptake, or processing of the radiolabeled analyte received at a cancer treatment site in a human subject based on the plurality of received measurements.

32. A computer program product according to claim 31, wherein the computer code for computing the dose is adapted to determine a patient-specific radiation dose received at a primary tumor site and at least one metastatic site.

33. A computer program product according to claim 31, further comprising computer readable program code for initiating operation of at least one implanted telemetric sensor proximate in time to each of a plurality of therapy sessions to obtain a plurality of discrete doses administered at temporally different points in time.

34. A computer program product according to claim 33, wherein further comprising computer program code for calculating a cumulative dose received at the target treatment site corresponding to a plurality of separate administered therapeutic doses of radiolabeled analytes.

35. A computer program product according to claim 33, further comprising computer readable program code for individually operating a plurality of telemetrically operable implanted sensors held in the subject to assess the amount of internal radiation received at a plurality of different sites.

36. A computer program product according to claim 35, wherein said computer program product includes computer program code for initiating the receipt of the measurements from a plurality of different sensors so as to wirelessly obtain a plurality of measurements from different sites, at least one in non-targeted treatment tissue and at least one in the target cancer treatment site, in the body over an active treatment period extending over a plurality of temporally spaced apart treatment sessions.

37. A computer program product according to claim 31, wherein the radiolabeled analyte is a therapeutic radiolabeled analyte, and wherein the computer readable program code for computing comprises computer readable program code for monitoring the uptake and utilization of the internally administered radiolabeled analyte at the cancer treatment site over a desired monitoring period.

38. A method for monitoring a patient undergoing treatment for cancer, comprising:

positioning at least one wireless sensor in tissue in a region of interest in the body of a patient being treated for cancer;

administering a therapeutic radioactive analyte internally to the patient;

detecting in vivo from the at least one sensor a signal corresponding to radiation in the region of interest in the patient responsive to the administering step;

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

monitoring the signal over time to determine the localized response of the patient to the administered analyte to provide patient-specific response data that can be used to develop a patient specific cancer treatment strategy and/or evaluate the clinical efficacy of the treatment in the patient.

39. A method according to claim 38, further comprising determining radiation dose, uptake and/or utilization based on the monitored signal response data.