Radiation Dosimetry on 18F-VAT in human

Objectives: bjective : We previously reported based on PET imaging in nonhuman primates human the radiation dosimetry estimates for [18F]-VAT[1], a novel radiotracer for vesicular acetylcholine transporter, (-)-(1-((2R,3R)-8-(2-[(18)F]fluoro-ethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone ([18F]VAT). This work estimates human radiation dosimetry from human PET images using this agent and compares the biodistribution relative to non-primate data.

Methods: Three human volunteers were imaged on an ECAT HR+ using the whole-body acquisition mode and multiple time points following injection of 370MBq of [18F]-VAT. Three dimensional region of interest that encompass the entire organs or sample of the organ to calculate average organ activity, were drawn on the organs showing visible uptake on the PET images. Organ time activity curves were created and organ residence times were calculated by analytical integration of multi-exponential fits. Residence times were entered in OLINDA/EXM for the adult anthropomorphic hermaphrodite model. All activity non-accounted for was assigned to the remainder of the body. Results: Organ radiation dosimetry revealed that the critical organ is the gallbladder with a dose of 104 uSv/MBq followed by the liver at 31 uSv/MBq. The effective Dose is 12 uSv/MBq. The human biodistribution revealed a similar biodistribution to the previously reported macaque study data but with less accumulation in the gallbladder. Conclusions: Both human and macaque biodistribution data showed high retention of [18F]-VAT in the liver and gallbladder consistent with hepatobiliary clearance. These dosimetry data support that relatively safe doses of [18F]-VAT can be administered to obtain imaging in humans. [1] Radiation dosimetry of [18F]VAT in nonhuman primates, M. Karimi, Z.Tu, X.Yue, X.Zhang, J. Jin, J. Perlmutter, R. Laforest, EJNMMI Res. 2015; 5:73.