Original article Amyloid plaque imaging agent [C-11]-6-OH-BTA-1: biodistribution and radiation dosimetry in baboon Ramin V. Parsey a,c , Levi O. Sokol c , Marie-Jose ´ Be ´ langer c , J.S. Dileep Kumar c , Norman R. Simpson b,c , Theodore Wang b , Mali Pratap c , Ronald L. Van Heertum c and J. John Mann a,b,c 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 biodis- tribution 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 transmis- sion 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 sub- sequent 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). Conclusion 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 Com- mittee (RDRC) to a single injection of 1295 MBq (35 mCi) in the adult male, and 1314 MBq (35 mCi) in the adult female. Nucl Med Commun 26:875–880  c 2005 Lippincott Williams & Wilkins. Nuclear Medicine Communications 2005, 26:875–880 Keywords: positron emission tomography, BTA, radiation dosimetry, amyloid Departments of a Psychiatry and b Radiology and Columbia University College of Physicians and Surgeons and Division of Brain Imaging and c Department of Neuroscience, New York State Psychiatric Institute, New York,10032, USA. Correspondence to Ramin Parsey M.D., Ph.D., New York State Psychiatric Institute, 1051 Riverside Drive, Box #42, New York,10032, USA. Tel: +1 212 543 6101; fax: +1 212 543 6017; e-mail: rparsey@neuron.cpmc.columbia.edu Received 16 March 2005 Accepted 2 June 2005 Introduction Alzheimer’s disease (AD) is a common form of dementia [1]. The disease progresses from mild cognitive impair- ment to significant loss of memory, decline in motor activity, and ultimately death [2]. Alzheimer’s disease is characterized by extracellular deposition of b-amyloid- containing senile plaques (SPs) and intracellular neurofi- brillary tangles (NFTs) comprised of a hyperphosphory- lated tau protein [3,4]. Since the progression of Alzheimer’s disease shows a significant correlation with levels of b-amyloid protein in brain, imaging agents for b-amyloid would potentially enable earlier diagnosis of AD, monitoring of the progression and regression of the disease, and be a biomarker of treatment response particularly for treatments considered to work by redu- cing amyloid protein load. Several small molecules have been identified as potential PET and SPECT tracers for AD [5]. [C-11]-6-OH-BTA-1 is one of the most promising PET agents for the in vivo imaging of amyloid in human subjects [6–9]. However, to date no radiation dose estimates in primates have been published for this ligand. This study reports the first radiation dose estimates of [C-11]-6-OH-BTA-1 from data gathered in nonhuman primates. Materials and methods Animals The baboon studies were performed according to protocols approved by the Columbia-Presbyterian Med- ical Center Animal Care Committee. Fasted animals were immobilized with ketamine (10 mg/kg i.m.) and anesthe- tized with 1.8% isoflurane via an endotracheal tube. Temperature was kept constant at 371C with heated water blankets. An intravenous line with 0.9% saline 0143-3636  c 2005 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.