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

Abstract

System for analyzing an in vivo response of a subject include a radiation detector for detecting radiation present in at least one localized solid tissue region of interest in a subject associated with internal activity of an administered quantity of an analyte comprising at least one of C-14 labeled glucose, a C-14 labeled constituent thereof, and a C-14 labeled glucose derivative, in the at least one solid tissue region of interest over a desired time interval of interest; and a reader in communication with the implantable detector for collecting radiation data from the detector associated with the detected radiation to determine at least one of the following; the in vivo dynamic, kinetic, and metabolic response of the subject.

1 . A system for detecting in vivo pharmacokinetic, pharmacodynamic and/or metabolic activity, comprising: 
 at least one radiation sensor configured to detect in vivo beta radiation at least intermittently over a period of time, the at least one sensor adapted to be positioned in solid tissue, and configured to detect the beta radiation as it is emitted in response to an administered analyte as the analyte is biochemically processed by the body, wherein the analyte comprises at least one of the following: radiolabeled glucose, a radiolabeled glucose constituent, and a radiolabeled glucose derivative; and    a processor operably associated with the at least one radiation sensor and configured to receive data associated with the detected radiation from the at least one sensor, wherein said processor is configured to electronically monitor selected in vivo parameters associated with one or more of the uptake, processing, and retention of at least one of the radiolabeled glucose, the radio labeled glucose constituent and the radiolabeled glucose derivative in the targeted localized solid tissue based on the data received from the at least one sensor.    
   
   
       2 . A system according to  claim 1 , wherein the radiolabel comprises C-14 (carbon 14), and wherein the processor includes 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 monitoring selected in vivo parameters associated with one or more of the uptake, processing, and retention of the C-14 labeled glucose, C-14 labeled glucose constituent or C-14 labeled derivative in the at least one targeted localized solid tissue.  
   
   
       3 . A system according to  claim 1 , wherein the sensor is configured as an implantable telemetric sensor adapted for chronic implantation in solid tissue proximate a tumor site, and wherein the processor is configured to evaluate the metabolic activity of the tumor site.  
   
   
       4 . A system according to  claim 1 , wherein the processor is held in a remote housing, and wherein the at least one sensor is configured to wirelessly transmit signals associated with the in vivo detected radiation to the processor over a period extending from at least about 1 week.  
   
   
       5 . A system according to  claim 4 , wherein the at least one sensor is inductively powered and configured to wirelessly transmit signals to the associated processor with the in vivo detected radiation over a desired investigational period.  
   
   
       6 . A system according to  claim 1 , wherein the at least one sensor is a plurality of discrete spatially separated sensors, including first and second sensors that are adapted to detect radiation emitted from respective first and second spatially separate locations in the body.  
   
   
       7 . A system according to  claim 6 , wherein the first location is associated with normal or non-diseased tissue and the second location is associated with diseased, impaired, abnormal, or cancerous tissue.  
   
   
       8 . A system according to  claim 1 , wherein the radiolabel comprises C-14, the system further comprising a remote reader configured to communicate with the at least one sensor, the reader comprising the processor and being configured to programmatically evaluate selected predictive variables or parameters associated with at least one of the uptake and retention of at least one of the C-14 labeled glucose, the C-14 labeled glucose constituent, and the C-14 labeled glucose derivative in the localized tissue to determine at least one of the following: the biological half life thereof, the amount of time the detected radiation is above a predetermined threshold level in the solid tissue, the amount of time that the radiation detected is increasing in the solid tissue, the peak value of the detected radiation in the solid tissue, the time at which the peak radiation level occurs in the solid tissue, and the decay rate of the detected radiation in the solid tissue.  
   
   
       9 . A system according to  claim 1 , wherein the radiolabel comprises C-14, and wherein the processor is configured to determine the concentration of at least one of the C-14 labeled glucose, the C-14 labeled constituent and the C-14 labeled derivative in the at least one localized region of interest.  
   
   
       10 . A system according to  claim 1 , wherein the processor is configured to determine a time-dependent profile of emitted radiation in the solid tissue.  
   
   
       11 . A system according to  claim 1 , wherein the radiolabel comprises C-14, and wherein said at least one sensor is configured to detect radiation related to biochemical processing of at least one of C-14 labeled 2-deoxyglucose and a C-14 labeled constituent thereof.  
   
   
       12 . A system according to  claim 1 , wherein the radiolabel comprise C-14, and wherein said at least one sensor is configured to detect radiation related to internal activity of C-14 labeled dextraglucose and a C-14 labeled constituent thereof.  
   
   
       13 . A system according to  claim 1 , wherein the radiolabel comprises C-14, and wherein said sensor is configured to detect radiation related to internal activity of an administered C-14 labeled glucose or C-14 glucose derivative, wherein the C-14 labeled glucose or glucose derivative is selected to have a modified glucose molecular chemical structure that is biocompatible and can be bio-chemically processed by the body.  
   
   
       14 . A system for analyzing an in vivo response of a subject, comprising: 
 an implantable radiation detector for detecting radiation present in at least one localized solid tissue region of interest in a subject associated with internal activity of an administered quantity of an analyte comprising at least one of C-14 labeled glucose, a C-14 labeled glucose constituent, and a C-14 labeled glucose derivative, in the at least one solid tissue region of interest over a desired time interval of interest; and    a reader in communication with the implantable detector for collecting radiation data from the detector associated with the detected radiation to determine at least one of the following: the in vivo dynamic, kinetic, and metabolic response of the subject.    
   
   
       15 . A system according to  claim 14 , wherein the detector is configured to detect the concentration of the analyte in the at least one localized region of interest.  
   
   
       16 . A system according to  claim 14 , wherein said detector is configured to detect radiation related to in vivo biochemical processing of C-14 labeled 2-deoxyglucose or a C-14 labeled derivative of 2-deoxyglucose.  
   
   
       17 . A system according to  claim 14 , wherein said detector is configured to detect radiation related to the internal activity of at least one of C-14 labeled dextraglucose and a C-14 labeled constituent thereof  
   
   
       18 . A system according to  claim 14 , wherein said detector is configured to detect radiation related to the internal activity of an administered C-14 labeled glucose derivative, wherein the C-14 labeled glucose derivative is selected to have a modified glucose molecule chemical structure that is biocompatible and can be bio-chemically processed by the body.  
   
   
       19 . A system according to  claim 14 , the reader further comprising a processor having a computer readable storage medium having computer readable program code embodied in said medium, said computer-readable program code comprising computer readable program code configured to receive and analyze signals associated with the biochemical processing of at least one of the C-14 labeled glucose, the C-14 labeled glucose constituent and the C-14 labeled glucose derivative and a corresponding radiolabeled biochemical constituent thereof in the body.  
   
   
       20 . A system according to  claim 14 , wherein the sensor is chronically implanted proximate a tumor treatment site, and wherein reader is configured to provide assess a likelihood of receptiveness of a tumor treatment site to a therapeutic cytotoxic treatment based on the monitored radiation data in the solid tissue proximate the tumor site.  
   
   
       21 . A system according to  claim 14 , wherein the reader is configured to repetitively obtain radiation measurement data in the solid tissue in substantially real time over a desired monitoring window to evaluate changes in physiological, biological and/or metabolic behavior of a tumor treatment site.  
   
   
       22 . A system for analyzing an in vivo response of a subject, comprising: 
 a radiation detector for detecting in vivo radiation present in at least one localized solid tissue region of interest in a subject associated with internal activity of an administered quantity of C-14 labeled 2-deoxyglucose in the at least one solid tissue region of interest over a desired time interval of interest; and    a reader in communication with the implantable detector for collecting radiation data from the detector associated with the detected radiation to determine at least one of the following: the in vivo dynamic, kinetic, and metabolic response of the subject.    
   
   
       23 . A system according to  claim 22 , wherein the reader is configured to assess whether a tumor treatment site is likely to be receptive to a therapeutic cytotoxic treatment based on the monitored radiation data in the solid tissue proximate the tumor site.  
   
   
       24 . A system according to  claim 22 , wherein the reader is configured to repetitively obtain radiation measurement data in substantially real time over a desired monitoring window to evaluate changes in physiological, biological and/or metabolic behavior of a tumor treatment site.  
   
   
       25 . A system for analyzing an in vivo response of a subject, comprising: 
 a radiation detector for detecting in vivo radiation present in at least one localized solid tissue region of interest in a subject associated with internal activity of an administered quantity of a C-14 labeled glucose derivative in the at least one solid tissue region of interest over a desired time interval of interest, wherein the glucose derivative is selected so that it has a modified glucose molecular chemical structure that is biocompatible and can be bio-chemically processed by the body; and    a reader in communication with the implantable detector for receiving and analyzing radiation data from the detector associated with at least one of the C-14 labeled glucose derivative and a C-14 labeled biochemical constituent thereof to determine at least one of the following: the in vivo dynamic, kinetic, and metabolic response of the subject.    
   
   
       26 . A system according to  claim 25 , and wherein the detected radiation is from solid tissue proximate a tumor site.  
   
   
       27 . A system according to  claim 25 , wherein the detector and reader operate proximate in time to and before a planned therapeutic treatment.  
   
   
       28 . A system according to  claim 26 , wherein the reader is configured to provide a predictive indication of a receptiveness of the tumor site to a therapeutic cytotoxic treatment based on the monitored radiation data in the solid tissue proximate the tumor site.  
   
   
       29 . A system according to  claim 25 , wherein the reader is configured to repetitively obtain radiation measurement data in substantially real time over a desired monitoring window to evaluate changes in physiological, biological and/or metabolic behavior of a tumor treatment site.  
   
   
       30 . A system for analyzing in vivo metabolic activity of a subject undergoing treatment for cancer, comprising: 
 detection means for detecting metabolic activity in vivo based on levels of radiation present in localized tissue in the subject over a time interval of interest in response to administration of a radiolabled glucose or glucose derivative; and    analyzing means for electronically analyzing the detected radiation data to determine the in vivo metabolic kinetic activity of the subject.