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

• US 20030012731A1
• Filed: 04/22/2002
• Published: 01/16/2003
• 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
• Granted Patent: US 7,011,814 B2
• Time in Patent Office: Days
• US Class Current: 424/1.49
• 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 the in vivo clinical efficacy of a treatment in a subject, comprising the steps of:

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

administering a radiolabeled analyte to a subject;

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

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

monitoring the signal over time to determine the localized response of the subject to the administered analyte.

2. A method according to claim 1, wherein the radiolabel is a beta radiation label.

3. A method according to claim 1, wherein the analyte is a therapeutic pharmaceutical drug or antibody configured to treat a selected physiologic or biologic condition, impairment, or disease, and the radiolabel comprises a beta radiation label, and wherein the beta radiation label is substantially transparent to the physiologic or biologic reaction of the drug or antibody in the body, and wherein said monitoring is carried out to predict or assess the in vivo clinical efficacy of a selected treatment.

4. A method according to claim 2, wherein the radiolabeled analyte is a C-14 labeled pharmaceutical grade version of a drug configured for administration to a subject, the C-14 labeled version of the drug being substantially transparent to the in vivo pharmacokinetics of the non-labeled version, and wherein said monitoring is carried out to predict or assess the in vivo clinical efficacy of a selected pharmaceutical drug and/or the pharmacokinetics and/or pharmacodynamics thereof.

5. A method according to claim 1, further comprising the step of processing the relayed signal to electronically generate a time-dependent measurement profile of radioactivity in the localized tissue to identify at least one predictor variable of interest.

6. A method according to claim 1, wherein said monitoring step determines that at least one of the uptake and retention of the radiolabeled analyte in the localized region is above a predetermined threshold level.

7. A method according to claim 6, wherein said monitoring step determines the rate of the increase and decay in the signal strength over time.

8. A method according to claim 1, wherein said monitoring step determines 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.

9. 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, at least one kinetic or static predictor variable associated with the uptake and/or retention of the radiation in the localized tissue, the predictor variable including at least one of:

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

(b) the biological ½

life of the detected radiation;

(c) the rate of increase of detected radiation;

(d) the rate of decrease of detected radiation;

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

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

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

10. A method according to claim 1, wherein the radiolabeled analyte is administered to the subject locally proximate to the region of interest.

11. A method according to claim 1, wherein the radiolabeled analyte is administered to the subject directly to the region of interest.

12. A method according to claim 1, wherein the radiolabeled analyte is administered to the subject systemically.

13. A method according to claim 1, wherein the radiolabeled analyte is administered to the subject as a first test dose amount, said monitoring step predicts whether the response of the subject to the first dose indicates the likelihood of a favorable response to the selected pharmaceutical treatment, and wherein said method further comprises the step of administering a therapeutic dose of the selected pharmaceutical treatment to the subject if a favorable response is indicated, and wherein the second therapeutic dose amount is greater than the first dose amount.

14. A method according to claim 1, wherein said monitoring step assesses the behavior of the radiolabeled analyte in vivo in the localized tissue and generates a predictive treatment outcome of a corresponding non-radiolabeled analyte based on the monitored behavior of the radiolabeled analyte.

15. A method according to claim 3, wherein the radiolabeled analyte comprises at least one of a radiolabeled pharmaceutical grade drug, a radiolabeled metabolite, and a radiolabeled antibody.

16. A method according to claim 1, wherein the radiolabeled analyte is a radiolabeled pharmaceutical cytotoxic agent and/or radiolabeled antibody, wherein the sensor is implanted in diseased tissue, and wherein said monitoring step comprises evaluating radiation emitted from the radiolabeled pharmaceutical and/or antibody in the diseased tissue to determine the uptake and retention of the radiolabeled pharmaceutical and/or antibody in the diseased tissue.

17. A method according to claim 16, wherein the diseased tissue is a cancerous tumor, and wherein said monitoring step comprises determining cancer cell sensitivity or receptiveness to the radiolabeled pharmaceutical agent.

18. A method according to claim 1, wherein the administered radiolabeled analyte comprises C-14 labeled glucose and the detected radiation is associated with radiation from the radiolabeled analyte and/or a corresponding radiolabeled biochemical constituent thereof.

19. A method according to claim 1, wherein the administered radiolabeled analyte 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.

20. A method according to claim 1, wherein the administered radiolabeled analyte comprises C-14 labeled 2-deoxyglucose.

21. A method according to claim 1, wherein the administered radiolabeled analyte comprises C-14 labeled dextraglucose

22. A method according to claim 1, wherein the administered radiolabeled analyte is C-14 labeled 5-FU.

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

24. A method according to claim 1, wherein said sensor is positioned spatially proximate a tumor, 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, said method further comprising the steps of:

administering a therapeutic treatment to the subject after said first radiolabeled analyte administering step; and

repeating said step of administering the radiolabeled analyte after said step of administering a therapeutic treatment to monitor changes in cell kinetics following a therapeutic treatment.

25. A method according to claim 1, wherein the radiolabeled analyte is a radiolabeled pharmaceutical drug and/or a radiolabeled antibody which is administered to the body in a test dose quantity, which is less than a therapeutic dose quantity.

26. A method according to claim 24, further comprising the step of selecting a subsequent pharmaceutical therapeutic treatment type based on said detecting and monitoring steps.

27. A method according to claim 25, further comprising the step of excluding certain types of treatment as being unlikely to be clinically effective based on said detecting and monitoring steps.

28. 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 or in a cancerous tumor.

29. A method according to claim 28, wherein the step of positioning is carried out so that the sensor is chronically implanted in the subject.

30. A method according to claim 29, 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.

31. A method according to claim 29, 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.

32. A method according to claim 1, wherein the sensor includes a fiber optic cable in communication with a photomultiplier tube (PMT), and wherein the step of positioning is carried out to place the fiber optic cable in the subject proximate the target site and the PMT external of the body.

33. 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.

34. A method according to claim 1, wherein the radiolabeled analyte is an antibody configured to provide radioimmunotherapy to the region of interest, and wherein said monitoring step determines the dose amount of radioimmunotherapy delivered to the region of interest.

35. 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 to determine the biokinetics of the tissue at different positions thereof.

36. 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 detecting step detects the biokinetics of both normal and cancerous tissue.

37. A method according to claim 1, wherein at least one of said sensors is implanted in localized tissue in the target region of interest and configured to operate wirelessly such that said relaying step is carried out telemetrically.

38. 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.

39. A method according to claim 1, wherein the radiolabeled analyte is a radiolabeled version of a pharmaceutical product undergoing clinical evaluation, and wherein the clinical efficacy evaluated in said monitoring step comprises determining whether the pharmaceutical product reaches the region of interest and/or the pharmacodynamics and/or pharmacokinetics thereof.

40. 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 clinical efficacy evaluated in said monitoring step comprises determining whether the pharmaceutical product is likely to be clinically effective or performs as intended based on said detecting step.

41. 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.

42. A method according to claim 1, wherein said monitoring step identifies the biological ½

life of the radiolabeled analyte and/or a radiolabeled biochemical constituent thereof at the region of interest.

43. A method according to claim 1, wherein said monitoring step determines the radiation activity 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 analyte or radiolabeled biochemical constituent thereof in tissue in the region of interest.

44. A method for determining the clinical efficacy of a pharmaceutical, antibody, and/or chemical product in a subject, comprising the steps of:

administering a first quantity of a C-14 radiolabeled version of a pharmaceutical product including a drug or antibody to a subject;

detecting a signal from an in situ sensor, the signal corresponding to the radiation responsive to the administered radiolabeled pharmaceutical product in a region of interest in the subject;

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

repeating said detecting and relaying steps over a duration of at least about 0.25-12 hours; and

monitoring the signals over time to determine the dynamic activity of the radiolabeled pharmaceutical product and/or a radiolabeled biochemical constituent in the region of interest of the subject.

45. A method according to claim 44, wherein the first quantity is less than a therapeutic quantity of a corresponding non-radiolabeled pharmaceutical product, and wherein said monitoring step is carried out to predict the in vivo clinical efficacy of a pharmaceutical product or the local tissue sensitivity or receptiveness thereto.

46. A method according to claim 44, wherein said administrating step is performed such that the radiolabeled pharmaceutical product is delivered locally to the region of interest.

47. A method according to claim 44, wherein said administrating step is performed such that the radiolabeled pharmaceutical product is injected locally.

48. A method according to claim 44, said method further comprising the step of electronically generating a time dependent measurement profile of in vivo radioactivity in the localized region of interest to provide at least one predictor variable, wherein said monitoring step evaluates whether the subject will respond favorably to a therapeutic treatment based on the at least one predictor variable.

49. A method according to claim 44, wherein the in situ sensor is positioned in vivo proximate a cancerous tumor, and wherein said administrating step is carried out proximate in time to and before a planned delivery of a therapeutic quantity of a chemotherapeutic drug or antibody to treat the tumor to thereby test the receptiveness of the tumor to the planned therapeutic treatment prior to delivering to the subject.

50. A method according to claim 44, 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 delayed treatment time.

51. A method according to claim 44, wherein the in situ sensor is placed in or proximate to a cancerous tumor in the body of a subject, and wherein said monitoring step comprises determining cancer cell sensitivity to a planned chemotherapy drug.

52. A method according to claim 44, wherein the sensor is located in a tumor, and wherein said administering step is carried out at a time proximate to a planned therapeutic treatment, and wherein said detecting step further comprising the step of determining if a tumor is likely to be responsive to the planned treatment based on said detecting and monitoring steps.

53. A method according to claim 52, wherein the radiolabeled product is administered to the body in a test dose quantity which is less than a therapeutic dose wherein said administering step is performed before and after a therapeutic treatment has been delivered to the subject.

54. A method according to claim 44, wherein the radiolabeled analyte is a radiolabeled version of a pharmaceutical product undergoing clinical evaluation, and wherein the clinical efficacy evaluated in said monitoring step comprises evaluating the pharmacokinetics and/or pharmacodynamics of the pharmaceutical product and/or the metabolic behavior of tissue in the region of interest.

55. A method according to claim 53, further comprising the step of selecting a subsequent therapeutic treatment based on said detecting and monitoring steps.

56. A method according to claim 55, further comprising the step of excluding certain types of treatment as being unlikely to be clinically effective based on said detecting and monitoring steps.

57. A method according to claim 44, wherein the sensor is positioned in the subject so that it resides proximate to or in a tumor in the region of interest, wherein the sensor is configured to directly detect emitted beta radiation in vivo.

58. A method according to claim 44, wherein the sensor is positioned in the subject so that it resides proximate to or in a tumor in the region of interest, wherein the sensor is configured to indirectly detect emitted beta radiation in vivo.

59. A method according to claim 44, wherein the sensor is chronically implantable and comprises electronics that are configured such that, in operation, the detected beta emitted radiation is wirelessly transmitted to a reader positioned external of the subject.

60. A method according to claim 59, wherein the sensor is a unitary body configured to directly and/or indirectly detect radiation.

61. A method according to claim 59, wherein the sensor includes two spaced apart bodies that are operably connected, a sensor probe body that is configured to be implanted at a target site and directly and/or indirectly detect radiation and a sensor processor body that is configured to be implanted at a lesser depth in the body so that it is subcutaneously positioned closer to the skin of the subject than the sensor probe body.

62. A method according to claim 44, wherein the sensor includes at least one fiber optic strand in communication with a photomultiplier tube, wherein, in position, the at least one fiber optic strand is configured to be positioned at the target site in the body of the subject and the photomultiplier tube is positioned in a housing located external of the body of the subject.

63. A method according to claim 44, wherein said detecting step comprises detecting a plurality of signals from a plurality of different in situ sensors, each signal corresponding to the radiation responsive to the administered radiolabeled pharmaceutical in the region of interest.

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

at least one radiation sensor configured for in vivo operation, the at least one sensor being configured to directly and/or indirectly detect beta radiation emitted from a radioactive analyte and/or a corresponding radiolabeled biochemical constituent thereof in or proximate to targeted localized tissue in the body, wherein the at least one sensor is configured to detect emitted beta radiation, at least intermittently, over a period of time extending from about 0.25-24 hours; and

a processor 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 processor includes computer program code for dynamically monitoring selected in vivo parameters associated with one or more of the uptake, processing, and retention of the radioactive analyte and/or a corresponding radiolabeled biochemical constituent thereof in the targeted localized tissue.

65. A system according to claim 64, wherein the sensor is configured as an implantable telemetric sensor configured for at least one of direct or indirect detection of radiation, having an elongated body with a width and length which is less than or equal to about 3 mm×

25 mm, respectively.

66. A system according to claim 64, wherein the at least one sensor is configured to wirelessly transmit signals associated with the in vivo detected radiation over a period extending from at least about 1 day -3months.

67. A system according to claim 64, wherein the at least one sensor is configured to wirelessly transmit signals associated with the in vivo detected radiation over a period extending from at least about 1 week.

68. A system according to claim 64, wherein the at least one sensor is a plurality of sensors, including first and second sensors that are adapted to detect radiation emitted from first and second spatially separate locations in the target region of interest.

69. A system according to claim 64, wherein the at least one sensor is a plurality of sensors configured to be individually activatable.

70. A system according to claim 68, wherein the first location is associated with normal or non-diseased tissue and the second location is associated with diseased, abnormal, or cancerous tissue.

71. A computer program product for evaluating an individual'"'"'s response to a planned cancer treatment regimen, the computer program product comprising a computer readable storage medium having computer readable program code embodied in said medium, said computer-readable program code comprising:

computer readable program code for receiving a first measurement of radiation detected in vivo in tissue located about a local targeted site in the body of a subject, the detected radiation corresponding to radiation emitted from a radiolabeled analyte administered internally to the subject and/or radiolabeled biochemical constituent thereof;

computer readable program code for receiving a second measurement of the radiation detected in the tissue located about the targeted site after the first measurement the detected radiation corresponding to radiation emitted from the radiolabeled analyte administered internally to the subject and/or radiolabeled biochemical constituent thereof; and

computer readable program code for generating a time-dependent measurement profile for evaluating selected parameters associated with at least one of the signal intensity, concentration, uptake and retention of the radiolabeled analyte or radiolabeled biochemical constituent thereof in the localized tissue of the subject based on the first and second measurements.

72. A computer program product according to claim 71, further comprising computer readable program code for obtaining the first and second measurements proximate in time to a planned therapy.

73. A computer program product according to claim 72, further comprising computer readable program code for determining the likelihood that the planned therapy will be clinically efficacious prior to delivery of the planned therapy.

74. A computer program product according to claim 71, wherein said computer program product includes computer program code for initiating the first and second measurements a plurality of times over an active treatment period extending at least about 1 day to 3 months.

75. A computer program product according to claim 71, wherein said computer program product includes computer program code for initiating the first and second measurements a plurality of times over an active treatment period extending at least about 1 week.

76. A computer program product according to claim 71, further comprising computer program code for receiving third and fourth measurements after the targeted site has been exposed to a first therapeutic treatment.

77. A computer program product according to claim 76, further comprising computer program code for receiving third and fourth measurements after a time which is temporally spaced by at least about 24 hours from the first and second measurements.

78. A computer program product according to claim 71, wherein said computer program product further comprises computer readable program code for assessing the concentration of the radiolabeled analyte delivered to the local targeted site.

79. A computer program product according to claim 71, wherein the computer readable program code for evaluating selected predictive variables or parameters associated with at least one of the uptake and retention of a radiolabeled analyte in the localized tissue evaluates at least one of:

the biological ½

life of the radiolabeled analyte and/or radiolabeled biochemical constituent thereof in the localized tissue, the amount of time the detected radiation is above a predetermined threshold level, the amount of time that the radiation detected is increasing, the peak value of the detected radiation, the time at which the peak radiation level occurs, and the decay rate of the detected radiation.

80. A computer program product according to claim 72, wherein the computer program code for determining the likelihood that the planned therapy will be clinically efficacious prior to delivery of the planned therapy is based on time-dependent radiation measurements associated with a test dose of a radiolabeled analyte administered to a subject.

81. A computer program product according to claim 71, further comprising computer readable code for intermittently obtaining the first and second measurements a plurality of times over a plurality of treatment sessions.

82. A computer program product according to claim 81, further comprising computer readable code for wirelessly transmitting the measurements from an implanted sensor in the body of the subject to a reader located external of the subject.

83. A computer program product for quantifying the amount of radiation delivered to tissue in a targeted local site in the body of a subject, the computer program product comprising a computer readable storage medium having computer readable program code embodied in said medium, said computer-readable program code comprising:

computer readable program code for receiving data associated with radiation detected in vivo in tissue located about a local targeted site in the body of a subject in response to an internally administered radioimmunology therapy;

computer readable program code for generating a time-dependent measurement profile of the detected radiation at the local site; and

computer readable program code for evaluating the amount of radiation delivered to the localized tissue based on the time-dependent measurement profile.

84. A method for quantifying the amount of radiation delivered to tissue in a targeted local site in the body of a subject in response to a selected radioimmunology internally administered therapy, comprising:

repeatedly detecting radiation in viva in tissue located about a local targeted site in the body of a subject a plurality of times over a response window; and

evaluating the signal intensity, uptake and retention of radiation in the local site over the response window to determine the amount of radiation delivered to the localized tissue from a radioimmunology therapeutic treatment based on the detecting step.

85. A method product according to claim 84, wherein the detected radiation is based on radiation which is internally administered to the subject as a therapeutic antibody or drug.

86. A system for analyzing in vivo metabolic activity of a subject, comprising:

detection means for detecting metabolic kinetic activity in vivo based on the levels of radiation present in a localized in vivo region of interest in the subject in response to an administered quantity of a radiolabeled analyte over a desired time interval of interest; and

analyzing means for analyzing data associated with the detected radiation to determine the in vivo metabolic kinetic activity of the subject.

87. A system according to claim 86, further comprising a biocompatible radiolabeled analyte configured for human or animal administration, wherein the detection means is adapted to detect the concentration activity of the radiolabeled analyte and/or radiolabeled biochemical constituent thereof in the region of interest.

88. A system according to claim 86, wherein the radiolabeled analyte is a radiolabeled version of a drug undergoing evaluation in a drug discovery program, and wherein said analyzing means comprises means for assessing the pharmacokinetics and/or pharmacodynamics of the radiolabeled version of the drug.

89. A system according to claim 86, wherein the radiolabeled analyte is a biocompatible C-14 radiolabeled analyte.

90. A system according to claim 86, wherein the radiolabeled analyte is an exogenous material that is radiolabeled.

91. A system according to claim 86, wherein the radiolabeled analyte is an endogenous material that is radiolabeled.

92. A system according to claim 86, wherein the radiolabeled analyte is a biocompatible C-14 labeled version of a selected pharmaceutical drug or antibody, wherein said analyzing means comprises means for assessing the pharmacokinetics and/or pharmacodynamics of the C-14 labeled pharmaceutical drug or antibody.

93. A system according to claim 92, wherein said analyzing means comprises means for assessing pharmacokinetics and/or pharmacodynamics related to the C-14 labeled pharmaceutical drug.

94. A system according to claim 86, wherein said detection means is configured to detect radiation related to the internal activity of C-14 labeled glucose and/or a C-14 labeled constituent thereof as it is biochemically processed by the body.

95. A system according to claim 86, wherein said detection means is configured to detect radiation related to the internal activity of a C-14 labeled cytotoxic agent or antibody.

96. A system according to claim 86, wherein said detection means is configured to detect radiation related to the internal activity of C-14 labeled 2-deoxyglucose.

97. A system according to claim 86, wherein said detection means is configured to detect radiation related to the internal activity of C-14 labeled dextraglucose and/or a C-14 labeled biochemical constituent thereof.

98. A system according to claim 86, wherein said detection means is configured to detect radiation related to the internal activity of 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.

99. A computer program product for evaluating an individual'"'"'s metabolic activity using an in vivo administered beta radiolabeled analyte or related radiolabeled metabolites, the computer program product comprising a computer readable storage medium having computer readable program code embodied in said medium, said computer-readable program code comprising:

computer readable program code for receiving data for a first measurement of radiation detected in vivo in tissue located about a local targeted site in the body of a subject, the detected radiation corresponding to radiation associated with a radiolabeled analyte and/or a corresponding radiolabeled biochemical constituent thereof administered internally to a subject;

computer readable program code for receiving data for a second measurement of the radiation detected in the tissue located about the targeted site after the first measurement, the detected radiation corresponding to radiation associated with the radiolabeled analyte administered internally to the subject and/or a corresponding radiolabeled biochemical constituent thereof; and

computer readable program code for monitoring the received data over time to evaluate the metabolic activity of the local targeted site.

100. A computer program product according to claim 99, wherein the radiolabeled analyte is C-14 labeled glucose, and wherein the computer program product is configured to receive and analyze signals associated with C-14 labeled glucose and/or a corresponding radiolabeled biochemical constituent thereof in the body.

101. A computer program product according to claim 99, wherein the radiolabeled analyte is C-14 labeled 2-deoxyglucose, and wherein the computer program product is configured to receive and analyze signals associated with C-14 labeled 2-deoxyglucose.

102. A computer program product according to claim 99, wherein the radiolabeled analyte is 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, and wherein the computer program product is configured to receive and analyze signals associated with C-14 labeled glucose derivative or a corresponding radiolabeled biochemical constituent thereof.

103. A computer program product according to claim 99, wherein the radiolabeled analyte is C-14 labeled cytotoxic agents, and wherein the computer program product is configured to receive and analyze signals associated with the administered C-14 labeled cytotoxic therapeutic agents.

104. A computer program product according to claim 103, wherein the cytotoxic agent is C-14 labeled 5-Fu.

105. A computer program product according to claim 99, wherein the computer program code repeatedly obtains additional first and second measurements over an active monitoring period of at least 0.25 hours.

106. A computer program product according to claim 99, wherein the active monitoring period is at least about 1 hour.

107. A computer program product according to claim 99, wherein the computer program is initiated to operate proximate in time to and before a planned therapeutic treatment.

108. A computer program product according to claim 107, wherein the computer program is initiated to operate proximate in time to and after a planned therapeutic treatment.

109. A computer program product according to claim 99, further comprising computer readable program code for evaluating the potential success of a planned therapeutic cytotoxic treatment based on the monitored data.

110. A computer program product according to claim 109, wherein the first and second received measurement data is obtained from at least first and second different spatially separate locations.

111. A computer program product according to claim 110, wherein the first location is proximate a tumor and the second location is proximate normal tissue.

112. A computer program product according to claim 99, further comprising computer program code for repetitively obtaining the first and second measurement data successively in substantially real time over a desired monitoring window to evaluate changes in physiological, biological and/or metabolic behavior.