Amyloid plaque imaging agent [C-11]-6-OH-BTA-1: biodistribution and radiation dosimetry in baboon.
BACKGROUND
The amyloid neuritic plaque is considered to be a toxic collection of amyloid-ss protein found in brain tissue in Alzheimer's disease. A neutral analogue of the amyloid-binding thioflavin-T (BTA), has been radiolabeled as [C-11]-6-OH-BTA-1. It crosses the blood brain barrier, and is a promising tracer for imaging plaques in vivo using positron emission tomography. We now report the biodistribution and dosimetry of [C-11]-6-OH-BTA-1 in baboons.


METHODS
Four 2-hour whole body studies were acquired in an ECAT ACCEL camera in two baboons after the bolus injection of [C-11]-6-OH-BTA-1. After 3.5 minute transmission scans performed per bed position prior to injection, emission scans were collected in 2-D mode over five bed positions. Regions of interest (ROI) were drawn around the brain, left and right lungs, heart, liver, gall bladder, left and right kidneys, spleen and urinary bladder. Since no fluid was removed from the baboons, total body radioactivity was calculated using the injected dose and a calibration factor determined from a cylinder phantom. The area under the curve (AUC) for each ROI was determined by trapezoidal integration of the first few points with subsequent points fit by a decreasing monoexponential. The AUC was then divided by counts in the total body, and resulting residence times were entered into the MIRDOSE3 program.


RESULTS
The animals tolerated the procedure well. The ligand was eliminated via the hepatobiliary and renal systems. In the adult male and female reference the gallbladder received the highest estimated radiation dose and was the critical organ (3.9E-02 mGy/MBq and 4.3E-02 mGy/MBq respectively).


CONCLUSIONS
In the United States, the absorbed dose to the gallbladder would limit [C-11]-6-OH-BTA-1 administered with the approval of a Radioactive Drug Research Committee (RDRC) to a single injection of 1295 MBq (35 mCi) in the adult male, and 1314 MBq (35 mCi) in the adult female.
Parsey
Ramin V
RV
Department of Psychiatry, Columbia University College of Physicians and Surgeons and Division of Brain Imaging cDepartment of Neuroscience, New York State Psychiatric Institute, New York 10032, USA. rparsey@neuron.cpmc.columbia.edu
Sokol
Levi O
LO
Bélanger
Marie-José
MJ
Kumar
J S Dileep
JS
Simpson
Norman R
NR
Wang
Theodore
T
Pratap
Mali
M
Van Heertum
Ronald L
RL
John Mann
J
J
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D010215:Papio; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011829:Radiation Dosage; D011874:Radiometry; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013844:Thiazoles / Q000032:analysis / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014915:Whole-Body Counting
C507573:(N-methyl-C-11)-2-(4-methylamino-phenyl)-6-hydroxybenzothiazole; D019275:Radiopharmaceuticals; D013844:Thiazoles