PT  - JOURNAL ARTICLE
AU  - Syahir Mansor
AU  - Richard Laforest
AU  - Zonghua Luo
AU  - Gregory Gaehle
AU  - Michael Nickels
AU  - Tammie Benzinger
AU  - Zhude Tu
TI  - Preliminary Human Dosimetry Studies of [11C]-CS1P1, a Novel PET Tracer for Targeting Sphingosine-1-Phosphate Receptor 1 (S1P1)
DP  - 2021 May 01
TA  - Journal of Nuclear Medicine
PG  - 1591--1591
VI  - 62
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/62/supplement_1/1591.short
4100  - http://jnm.snmjournals.org/content/62/supplement_1/1591.full
SO  - J Nucl Med2021 May 01; 62
AB  - 1591Introduction: Molecular imaging of S1P1 expression in the brain provides an important biomarker for elucidating the pathophysiological roles of S1P1 in neuroinflammation and neurodegeneration. We previously reported the radiation dosimetry estimates for [11C]-CS1P1 using PET imaging and ex-vivo biodistribution in rodent. This report provides preliminary safety information from human whole-body biodistribution and dosimetry studies of [11C]-CS1P1 for its potential application in human brain imaging studies. 266.4 and 98.79 MBq of [11C]-CS1P1 was administered intravenously in two normal participants (one male and one female). Shortly after the administration of [11C]-CS1P1, whole body (WB) dynamic acquisition were initiated using Siemens Vision Biograph PET/CT (Siemens, Erlangen, Germany). The emission data were acquired for 180 minutes in 25 WB continuous bed motion sweeps from head to upper thighs. The time per sweeps were 120 s [for WB 1-10], 300 s [for WB 11-15], 600 s [for WB 16 and 20]) and 900 s [for WB 21 and 25]. A low-dose CT was performed before the PET emisision scan for PET attenuation correction and anatomical information. Scans were reconstructed using the ordered subset expectation maximization (OSEM) algorithm (4 iterations and 5 subsets) with a time of flight (TOF) and point spread function (PSF). Three-dimensional volumes of interest (VOIs) over entire organs were manually delineated on PET images using CT for anatomical localization. Eleven organs (lung, brain, kidney, gall bladder, spleen, liver, cardiac, stomach, urinary bladder, intestine and pancreas) were identified as source organs and remainder of the body that significantly took up the tracer and visually assessable amounts over the entire time frame of acquisition. Time-activity curves were obtained for each source organ by calculating the total activity (non decay corrected) in the VOIs and expressing them as the percentage of the total injected activity. Depending on the kinetics, different exponential models reflecting biodistribution and elimination of the tracer were used for different organs. The integrated-time-activity values were entered into a human biodistribution model Internal Dose Assessment by Computer (IDAC-Dose) (Ver. 2.1, Umeå University, Sweden). The IDAC-Dose software calculates effective dose (ED) from the individual organ doses with radiation weighting factors and organ weighting factors for each of the source organs based on ICRP Publications 103 for male while ICRP Publications 60 for female. The residence time for all source organs are given in Table 1. The organ with the largest residence time was the liver with 0.064 h while the smallest was the urinary bladder with 0.00030 h. The organ total absorbed doses per MBq were largest for the liver (9.88 ± 0.03 µGy/ MBq), (Table 1). The total effective dose (ED) per MBq of injected activity of [11C]-CS1P1 in human is 1.60 ± 0.15 µSv/MBq. Based on the preliminary results, the radiation doses from PET studies are minimal and any biologically harmful effects on humans are unlikely. The total radiation burden depends largely on the initial organ perfusion and its retention until it clears out (larger effective half-life). Highly perfused organs such as heart, lung, liver, kidney, and brain receive a larger fraction of the absorbed dose due to larger effective half-life; whereas, less perfused organs such as muscle or fat receive a much smaller fraction. Most radiotracer molecules are likely to be cleared via either hepatobiliary (liver, gallbladder) or renal excretion (kidneys, urinary bladder). In our preliminary findings, the liver is a critical dose-limiting organ for [11C]-CS1P1. From our preliminary results, imaging with [11C]-CS1P1 for clinical PET studies is safe. Administration of 10 mCi (370 MBq) of [11C]-CS1P1 is expected to resulting in a total human effective dose of <0.6 mSv and thus allow for multiple PET scans of the same subject per year.