title: Radiation dosimetry and biodistribution of the translocator protein radiotracer [(11)C]DAA1106 determined with PET/CT in healthy human volunteers.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  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 [(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).
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System (VAGLAHS), 11301 Wilshire Blvd., Los Angeles, CA 90073; Department of Psychiatry, University of California at Los Angeles, 300 UCLA Medical Plaza, Suite 2200, Los Angeles, CA 90095. Electronic address: abrody@ucla.edu.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Brody
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System (VAGLAHS), 11301 Wilshire Blvd., Los Angeles, CA 90073; UCLA Laboratory of Molecular Imaging, 760 Westwood Plaza C8-538, Los Angeles, CA 90095.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Okita
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System (VAGLAHS), 11301 Wilshire Blvd., Los Angeles, CA 90073.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Shieh
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System (VAGLAHS), 11301 Wilshire Blvd., Los Angeles, CA 90073.
authors.forename: Lidia
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System (VAGLAHS), 11301 Wilshire Blvd., Los Angeles, CA 90073.
authors.forename: Robert
authors.initials: R
authors.lastname: Hubert
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System (VAGLAHS), 11301 Wilshire Blvd., Los Angeles, CA 90073.
authors.forename: Michael
authors.initials: M
authors.lastname: Mamoun
authors.affiliation: Department of Imaging, VAGLAHS, 11301 Wilshire Blvd., Los Angeles, CA 90073.
authors.forename: Judah
authors.initials: J
authors.lastname: Farahi
authors.affiliation: Department of Imaging, VAGLAHS, 11301 Wilshire Blvd., Los Angeles, CA 90073; Department of Physics, University of California at Irvine, 4129 Frederick Reines Hall, Irvine, CA 92697.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
mesh_terms: D000081:Acetamides / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D010647:Phenyl Ethers / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018079:Receptors, GABA / Q000378:metabolism*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; C118942:DAA 1106; D010647:Phenyl Ethers; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: Dosimetry; Neuroinflammation; Positron emission tomography; Review; Translocator protein; [(11)C]DAA1106