Systems, methods and devices for in vivo monitoring of a localized response via a radiolabeled analyte in a subject

• US 7,011,814 B2
• Filed: 04/22/2002
• Issued: 03/14/2006
• Est. Priority Date: 04/23/2001
• Status: Active Grant

• Current Assignee: SNC Holdings Corp.
• Original Assignee: Sicel Technologies, Inc.
• Inventors: Black, Robert D., Scarantino, Charles W., Suddarth, Steven
• Primary Examiner(s): HARTLEY, MICHAEL G
• Application Number:
  US10/127,207
• Publication Number:
  US 20030012731A1
• Time in Patent Office: 1,422 Days
• Field of Search: 424/9.2, 424/9.1, 424/1.81, 600/300, 600/301, 600/407, 600/326
• US Class Current: 424/9.2
• CPC Class Codes: A61B 6/037 Emission tomography
• CPC Class Codes: A61B 6/486 involving generating temporal series of image data
• CPC Class Codes: A61B 6/507 for determination of haemodynamic parameters, e.g. perfusion CT
• CPC Class Codes: A61B 6/508 for non-human patients
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers

Abstract

Methods, systems, devices and computer program products monitor in vivo detected radiation in a target localized site within a subject, over a selected time period, to do one or more of: (a) quantify a radiation dose received at a local site; (b) assess bioreceptiveness to a particular treatment time or type; (c) evaluate the pharmacokinetics of a radiolabeled analyte corresponding to a non-radiolabeled analyte; (d) monitor or evaluate metabolic activity; or (e) evaluate a tumor prior to or after a therapeutic treatment.

Claims

1. A method for determining whether to administer a therapeutic amount of a chemotherapeutic drug for tumor treatment by determining an in vivo localized uptake response in solid tissue in a patient, comprising the steps of:

positioning at least one sensor in vivo in solid tissue in a region of interest in the body of the patient;

administering a test dose of a C-14 radiolabeled chemotherapeutic drug to the patient;

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

monitoring the signal over time to determine a localized uptake response in the solid tissue of the patient based on the administered test dose; and

determining whether to administer a therapeutic amount of a non-radiolabled version of the chemotherapeutic drug based on the determined localized uptake response to the test dose.

2. A method according to claim 1, further comprising:

wirelessly relaying the data to an external reader; and

processing the relayed signal to electronically generate a time dependent measurement profile of radioactivity in localized solid tissue to identify at least one predictor variable of interest to assess the drug uptake response in the solid tissue.

3. A method according to claim 1, wherein said determining step determines whether uptake and retention of the radiolabeled test dose in the localized solid tissue is above a predetermined threshold level.

4. A method according to claim 3, wherein said determining step determines the rate of the increase and decay in the signal strength over time.

5. A method according to claim 1, wherein said determining step determines at least one of the following;

the amount of time the detected signal remains above a threshold level, the time the signal takes to reach a peak level, the time the signal takes to decay to below a threshold value, and the rate of decay from the peak to the threshold value.

6. A method according to claim 1, wherein said monitoring step monitors, over a period of at least about 15 minutes from the time said administering step is initiated, and wherein said determining step determines at least one kinetic and/or static predictor variable associated with the uptake response of the radiation in the localized solid tissue, the predictor variable including at least one of the following:

(a) a time at which a detected peak radiation occurs;

(b) biological ½

life of the detected radiation;

(c) rate of increase of detected radiation;

(d) rate of decrease of detected radiation;

(e) a time at which the detected radiation falls a predetermined amount below the peak detected value;

(f) a duration of time that the detected radiation signal increases in strength; and

(g) a time during the monitored period when the detected radiation signal begins to decay.

7. A method according to claim 1, wherein the test dose is administered to the subject locally proximate to the region of interest.

8. A method according to claim 1, wherein the test dose is administered to the subject directly to the region of interest.

9. A method according to claim 1, wherein the test dose is administered to the subject systemically.

10. A method according to claim 1, wherein said determining step comprises generating a patient specific predictive treatment outcome of a planned drug therapy based on the monitored behavior of the test dose.

11. A method according to claim 1, wherein the sensor is implanted in solid tissue at a tumor treatment site, and wherein said determining step comprises evaluating radiation emitted from the C-14 radiolabeled test dose in the localized solid tissue to predict the likelihood of the respective patient having a favorable response to a known chemotherapeutic to thereby provide a patient-specific oncologic treatment evaluation.

12. A method according to claim 11, wherein the tumor treatment site comprises cancerous and/or precancerous cells, and wherein said monitoring step comprises determining cancer cell sensitivity and/or receptiveness to the radiolabeled test dose.

13. A method according to claim 1, wherein the administered radiolabeled test dose comprises C-14 labeled glucose.

14. A method according to claim 1, wherein the administered radiolabeled test dose comprises a C-14 labeled glucose derivative, wherein the glucose derivative is selected so that it has a modified glucose molecule chemical structure that is biocompatible and can be bio-chemically processed by the body.

15. A method according to claim 1, wherein the administered radiolabeled test dose comprises C-14 labeled 2-deoxyglucose.

16. A method according to claim 1, wherein the administered radiolabeled test dose comprises C-14 labeled dextraglucose.

17. A method according to claim 1, wherein the administered C-14 radiolabeled test dose comprises C-14 labeled 5-FU.

18. A method according to claim 1, further comprising evaluating metabolic activity in the subject based on data collected during said monitoring step.

19. A method according to claim 1, wherein said sensor is positioned in solid tissue spatially proximate a tumor site, and wherein said administering step is first carried out at a time which is proximate to a first planned therapeutic cancer treatment, said method further comprising:

administering a second test dose of the C-14 radiolabeled chermotherapeutic drug after the first test dose and after after administering a therapeutic treatment to monitor changes in cell kinetics following a therapeutic treatment.

20. A method according to claim 19, further comprising the step of selecting a subsequent therapeutic treatment type based on said determining step.

21. A method according to claim 1, further comprising identifying at least one type of known cancer treatment as being unlikely to be clinically effective for the respective patient in generally real-time based on said monitoring and determining steps.

22. 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 at least one sensor resides in solid tissue proximate to and/or in a cancerous tumor site.

23. A method according to claim 22, wherein the step of positioning is carried out so that the sensor is chronically implanted in the subject.

24. A method according to claim 23, wherein the sensor is a unitary body implantable sensor configured to detect radiation in at least one of a director indirect mode of detection and wirelessly communicate the detected radiation data to an externally located reader.

25. A method according to claim 23, 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.

26. A method according to claim 1, wherein the at least one sensor is a plurality of sensors, each positioned in different locations in the body of the subject.

27. A method according to claim 1, wherein the test dose of the C-14 radiolabeled chemotherapeutic drug comprises an antibody for treating cancer.

28. 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 test dose at a plurality of different solid tissue locations in vivo within the region of interest to determine the biokinetics of the tissue at different positions thereof.

29. A method according to claim 1, 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 determining step comprises determining uptake in both normal and cancerous tissue.

30. A method according to claim 1, wherein said at least one sensor is implanted in solid tissue in the target region of interest and configured to operate wirelessly.

31. A method according to claim 1, wherein the radiolabeled test dose is is a radiolabeled version of a chemotherapeutic drug undergoing clinical evaluation, and wherein the determining step comprises generating a patient-specific time dependent response profile for determining whether the pharmaceutical product reaches the region of interest and/or the pharmacodynamics and/or pharmacokinetics thereof.

32. A method according to claim 1, wherein said monitoring step is carried out such that the radioactivity in the region of interest is monitored for a period of at least about 15 minutes, and wherein the determining step comprises predicting whether a therapeutic amount of the non-radiolabeled version of the chemotherapeutic agent is likely to be clinically effective for the particular subject based on said determining step and a priori data that defines at least one predetermined predictor variable associated with the uptake response.

33. A method according to claim 1, wherein said detecting step is at least periodically performed over a period of time extending for at least between about 0.25-24 hours.

34. A method according to claim 1, wherein said determining step identifies the biological ½

life of the test dose in the solid tissue.

35. A method according to claim 1, wherein said monitoring and/or determining steps determine the radiation activity in the solid tissue at a plurality of points in time and then determines at least one of the pharmacokinetic, the pharmacodynamic, and/or the biokinetic response to the radiolabeled test dose in solid tissue in the region of interest.

36. A method according to claim 1, wherein the radiolabeled test dose comprises a known anti-cancer chemotherapeutic drug with a priori data associating clinical efficacy to dose, retention and/or uptake of the anti-cancer drug at a tumor treatment site.

37. A method according to claim 1, wherein the determining the response profile comprises determining whether a tumor site is taking up and/or retaining the radiolabeled test dose.

38. A method according to claim 1, wherein the monitoring and determining are carried out to determine whether the radiation from the radiolabeled analyte exhibits a ½

life greater than about 15 minutes at a target localized tumor treatment site.

39. A method for predicting, on a patient-specific basis, a likelihood of response to a known chemotherapeutic agent in a tumor site of a respective patient, comprising:

chronically positioning at least one sensor in vivo in solid tissue proximate a tumor site in a patient'"'"'s body;

administering a test dose of a C-14 radiolabeled chemotherapeutic agent;

detecting in vivo from the at least one sensor a signal over time corresponding to radiation proximate the tumor site in response to the administering step;

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

determining a patient-specific in vivo uptake response of the C-14 radiolabeled test dose in solid tissue proximate the tumor site based on the relayed radiation signal; and

determining whether to administer a therapeutic amount of a non-radiolabeled version of the chemotherapeutic agent based on the determined uptake response.

40. A method according to claim 39, wherein the determining step comprises comparing at least one predetermined predictor parameter associated with the uptake response in a patient-specific response profile to a corresponding at least one a priori predictor standard indicating the C-14 radiolabeled test dose is retained at or above a target level in the solid tissue proximate the tumor site for a target time.

41. A method according to claim 40, wherein the at least one predictor parameter comprises a C-14 half-life at the tumor site that is above about 15 minutes.

42. A method according to claim 39, the method further comprising administering the therapeutic dose amount of the non-radiolabeled chemotherapeutic agent to the patient if a favorable response is predicted by said determining whether to administer step.

43. A method according to claim 39, wherein the patient is a human, and wherein the determining whether to administer step comprises evaluating the patient uptake response to determine a likely treatment outcome of the corresponding therapeutic amount of the non-radiolabeled chemotherapeutic agent based on the monitored patient-specific uptake behavior of the radiolabeled test dose in the patient.

44. A method according to claim 39, wherein the administered C-14 labeled test dose of the chemotherapeutic agent comprises C-14 labeled glucose.

45. A method according to claim 39, wherein the administered C-14 labeled test dose of the chemotherapeutic agent comprises a C-14 labeled glucose derivative, wherein the glucose derivative is selected so that it has a modified glucose molecule chemical structure that is biocompatible and can be bio-chemically processed by the body.

46. A method according to claim 39, wherein the administered C-14 labeled test dose of the chemotherapeutic agent comprises C-14 labeled 2-deoxyglucose.

47. A method according to claim 39, wherein the administered C-14 labeled test dose of the chemotherapeutic agent comprises C-14 labeled dextraglucose.

48. A method according to claim 39, wherein the administered C-14 test dose comprises C-14 labeled 5-FU.

49. A method according to claim 39, wherein the administered C-14 test dose comprises a C-14 labeled antibody.

50. A method according to claim 39, wherein the determining step comprises generating a time-dependent patient uptake response profile.