VA Greater Los Angeles Healthcare System VAGLAHS

Los Angeles, CA, United States

VA Greater Los Angeles Healthcare System VAGLAHS

Los Angeles, CA, United States
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Brody A.L.,University of California at Los Angeles | Okita K.,VA Greater Los Angeles Healthcare System VAGLAHS | Shieh J.,VA Greater Los Angeles Healthcare System VAGLAHS | Liang L.,VA Greater Los Angeles Healthcare System VAGLAHS | And 4 more authors.
Nuclear Medicine and Biology | Year: 2014

Introduction: When microglia become activated (an integral part of neuroinflammation), cellular morphology changes and expression of translocator protein (TSPO) 18 kDa is increased. Over the past several years, [11C]DAA1106 has emerged as a reliable radiotracer for labeling TSPO with high affinity during positron emission tomography (PET) scanning. While [11C]DAA1106 PET scanning has been used in several research studies, a radiation dosimetry study of this radiotracer in humans has not yet been published. Methods: Twelve healthy participants underwent full body dynamic [11C]DAA1106 PET scanning, with 8 sequential whole body scans (approximately 12 bed positions each), following a single injection. Regions of interest were drawn manually, and time activity curves (TACs) were obtained for 15 organs. OLINDA/EXM 1.1 was used to compute radiation absorbed doses to the target organs, as well as effective dose (ED) and effective dose equivalent (EDE). Results: The ED and EDE were 4.06 ± 0.58 μSv/MBq and 5.89 ± 0.83 μSv/MBq, respectively. The highest absorbed doses were to the heart wall, kidney, liver, pancreas, and spleen. TACs revealed that peak dose rates are during the first scan (at 6 min) for all organs other than the urinary bladder wall, which had its peak dose rate during the fourth scan (at 30 min). Conclusions: The recently developed radiotracer [11C]DAA1106 has its EDE and target-organ absorbed dose such that, for a single administration, its radiation dosimetry is well within the U.S. FDA guidelines for basic research studies in adults. This dose level implies that the dosimetry for multiple [11C]DAA1106 scans within a given year also falls within FDA guidelines, and this favorable property makes this radiotracer suitable for examining microglial activation repeatedly over time, which may in the future be useful for longitudinal tracking of disease progression and monitoring of therapy response in conditions marked by neuroinflammation (e.g., head trauma and multiple sclerosis).


Koek R.J.,VA Greater Los Angeles Healthcare System VAGLAHS | Koek R.J.,University of California at Los Angeles | Langevin J.-P.,University of California at Los Angeles | Krahl S.E.,University of California at Los Angeles | And 10 more authors.
Trials | Year: 2014

Background: Combat post-traumatic stress disorder (PTSD) involves significant suffering, impairments in social and occupational functioning, substance use and medical comorbidity, and increased mortality from suicide and other causes. Many veterans continue to suffer despite current treatments. Deep brain stimulation (DBS) has shown promise in refractory movement disorders, depression and obsessive-compulsive disorder, with deep brain targets chosen by integration of clinical and neuroimaging literature. The basolateral amygdala (BLn) is an optimal target for high-frequency DBS in PTSD based on neurocircuitry findings from a variety of perspectives. DBS of the BLn was validated in a rat model of PTSD by our group, and limited data from humans support the potential safety and effectiveness of BLn DBS.Methods/Design: We describe the protocol design for a first-ever Phase I pilot study of bilateral BLn high-frequency DBS for six severely ill, functionally impaired combat veterans with PTSD refractory to conventional treatments. After implantation, patients are monitored for a month with stimulators off. An electroencephalographic (EEG) telemetry session will test safety of stimulation before randomization to staggered-onset, double-blind sham versus active stimulation for two months. Thereafter, patients will undergo an open-label stimulation for a total of 24 months. Primary efficacy outcome is a 30% decrease in the Clinician Administered PTSD Scale (CAPS) total score. Safety outcomes include extensive assessments of psychiatric and neurologic symptoms, psychosocial function, amygdala-specific and general neuropsychological functions, and EEG changes. The protocol requires the veteran to have a cohabiting significant other who is willing to assist in monitoring safety and effect on social functioning. At baseline and after approximately one year of stimulation, trauma script-provoked 18FDG PET metabolic changes in limbic circuitry will also be evaluated.Discussion: While the rationale for studying DBS for PTSD is ethically and scientifically justified, the importance of the amygdaloid complex and its connections for a myriad of emotional, perceptual, behavioral, and vegetative functions requires a complex trial design in terms of outcome measures. Knowledge generated from this pilot trial can be used to design future studies to determine the potential of DBS to benefit both veterans and nonveterans suffering from treatment-refractory PTSD. © 2014 Koek et al.; licensee BioMed Central Ltd.


Brody A.L.,VA Greater Los Angeles Healthcare System VAGLAHS | Brody A.L.,University of California at Los Angeles | Okita K.,VA Greater Los Angeles Healthcare System VAGLAHS | Okita K.,University of California at Los Angeles | And 7 more authors.
Nuclear Medicine and Biology | Year: 2014

Introduction: When microglia become activated (an integral part of neuroinflammation), cellular morphology changes and expression of translocator protein (TSPO) 18kDa is increased. Over the past several years, [11C]DAA1106 has emerged as a reliable radiotracer for labeling TSPO with high affinity during positron emission tomography (PET) scanning. While [11C]DAA1106 PET scanning has been used in several research studies, a radiation dosimetry study of this radiotracer in humans has not yet been published. Methods: Twelve healthy participants underwent full body dynamic [11C]DAA1106 PET scanning, with 8 sequential whole body scans (approximately 12 bed positions each), following a single injection. Regions of interest were drawn manually, and time activity curves (TACs) were obtained for 15 organs. OLINDA/EXM 1.1 was used to compute radiation absorbed doses to the target organs, as well as effective dose (ED) and effective dose equivalent (EDE). Results: The ED and EDE were 4.06 ± 0.58. μSv/MBq and 5.89 ± 0.83. μSv/MBq, respectively. The highest absorbed doses were to the heart wall, kidney, liver, pancreas, and spleen. TACs revealed that peak dose rates are during the first scan (at 6. min) for all organs other than the urinary bladder wall, which had its peak dose rate during the fourth scan (at 30. min). Conclusions: The recently developed radiotracer [11C]DAA1106 has its EDE and target-organ absorbed dose such that, for a single administration, its radiation dosimetry is well within the U.S. FDA guidelines for basic research studies in adults. This dose level implies that the dosimetry for multiple [11C]DAA1106 scans within a given year also falls within FDA guidelines, and this favorable property makes this radiotracer suitable for examining microglial activation repeatedly over time, which may in the future be useful for longitudinal tracking of disease progression and monitoring of therapy response in conditions marked by neuroinflammation (e.g., head trauma and multiple sclerosis). © 2014 .


PubMed | VA Greater Los Angeles Healthcare System VAGLAHS, University of California at Irvine, University of California at Los Angeles and VAGLAHS
Type: Journal Article | Journal: Nuclear medicine and biology | Year: 2014

When microglia become activated (an integral part of neuroinflammation), cellular morphology changes and expression of translocator protein (TSPO) 18 kDa is increased. Over the past several years, [(11)C]DAA1106 has emerged as a reliable radiotracer for labeling TSPO with high affinity during positron emission tomography (PET) scanning. While [(11)C]DAA1106 PET scanning has been used in several research studies, a radiation dosimetry study of this radiotracer in humans has not yet been published.Twelve healthy participants underwent full body dynamic [(11)C]DAA1106 PET scanning, with 8 sequential whole body scans (approximately 12 bed positions each), following a single injection. Regions of interest were drawn manually, and time activity curves (TACs) were obtained for 15 organs. OLINDA/EXM 1.1 was used to compute radiation absorbed doses to the target organs, as well as effective dose (ED) and effective dose equivalent (EDE).The ED and EDE were 4.06 0.58 Sv/MBq and 5.89 0.83 Sv/MBq, respectively. The highest absorbed doses were to the heart wall, kidney, liver, pancreas, and spleen. TACs revealed that peak dose rates are during the first scan (at 6 min) for all organs other than the urinary bladder wall, which had its peak dose rate during the fourth scan (at 30 min).The recently developed radiotracer [(11)C]DAA1106 has its EDE and target-organ absorbed dose such that, for a single administration, its radiation dosimetry is well within the U.S. FDA guidelines for basic research studies in adults. This dose level implies that the dosimetry for multiple [(11)C]DAA1106 scans within a given year also falls within FDA guidelines, and this favorable property makes this radiotracer suitable for examining microglial activation repeatedly over time, which may in the future be useful for longitudinal tracking of disease progression and monitoring of therapy response in conditions marked by neuroinflammation (e.g., head trauma and multiple sclerosis).


Koek R.J.,VA Greater Los Angeles Healthcare System VAGLAHS | Langevin J.-P.,VA Greater Los Angeles Healthcare System VAGLAHS | Krahl S.E.,VA Greater Los Angeles Healthcare System VAGLAHS | Kosoyan H.J.,VA Greater Los Angeles Healthcare System VAGLAHS | And 5 more authors.
Trials | Year: 2014

BACKGROUND: Combat post-traumatic stress disorder (PTSD) involves significant suffering, impairments in social and occupational functioning, substance use and medical comorbidity, and increased mortality from suicide and other causes. Many veterans continue to suffer despite current treatments. Deep brain stimulation (DBS) has shown promise in refractory movement disorders, depression and obsessive-compulsive disorder, with deep brain targets chosen by integration of clinical and neuroimaging literature. The basolateral amygdala (BLn) is an optimal target for high-frequency DBS in PTSD based on neurocircuitry findings from a variety of perspectives. DBS of the BLn was validated in a rat model of PTSD by our group, and limited data from humans support the potential safety and effectiveness of BLn DBS.METHODS/DESIGN: We describe the protocol design for a first-ever Phase I pilot study of bilateral BLn high-frequency DBS for six severely ill, functionally impaired combat veterans with PTSD refractory to conventional treatments. After implantation, patients are monitored for a month with stimulators off. An electroencephalographic (EEG) telemetry session will test safety of stimulation before randomization to staggered-onset, double-blind sham versus active stimulation for two months. Thereafter, patients will undergo an open-label stimulation for a total of 24 months. Primary efficacy outcome is a 30% decrease in the Clinician Administered PTSD Scale (CAPS) total score. Safety outcomes include extensive assessments of psychiatric and neurologic symptoms, psychosocial function, amygdala-specific and general neuropsychological functions, and EEG changes. The protocol requires the veteran to have a cohabiting significant other who is willing to assist in monitoring safety and effect on social functioning. At baseline and after approximately one year of stimulation, trauma script-provoked 18FDG PET metabolic changes in limbic circuitry will also be evaluated.DISCUSSION: While the rationale for studying DBS for PTSD is ethically and scientifically justified, the importance of the amygdaloid complex and its connections for a myriad of emotional, perceptual, behavioral, and vegetative functions requires a complex trial design in terms of outcome measures. Knowledge generated from this pilot trial can be used to design future studies to determine the potential of DBS to benefit both veterans and nonveterans suffering from treatment-refractory PTSD.TRIAL REGISTRATION: PCC121657, 19 March 2014.

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