Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand ¹⁸F-FE-PE2I in Human Subjects

Abstract

F-()--(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'-methyl-phenyl) nortropane (F-FE-PE2I) was recently developed and has shown adequate affinity and high selectivity for the dopamine transporter (DAT). Previous studies have shown promising results for F-FE-PE2I as a suitable radioligand for DAT imaging. In this study, we investigated the whole-body biodistribution and dosimetry ofF-FE-PE2I in healthy volunteers to support its utility as a suitable PET imaging agent for the DAT. Five healthy volunteers were given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were performed immediately after injection followed by 4 whole-body PET/CT scans between 0.5 and 6 h after injection. Blood samples were drawn in connection with the whole-body scans, and all urine was collected until 6 h after injection. Volumes of interest were delineated around 17 organs on all images, and the areas under the time-activity curves were calculated to obtain the total number of decays in the organs. The absorbed doses to organs and the effective dose were calculated using the software IDAC. The highest activity concentration was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after injection. At later time points, the highest concentration was seen in the gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the highest absorbed dose (119 μGy/MBq), followed by the liver (46 μGy/MBq). The effective dose was 23 μSv/MBq (range, 19-28 μSv/MBq), resulting in an effective dose of 4.6 mSv for an administered activity of 200 MBq. The effective dose is within the same order of magnitude as other commonly used PET imaging agents as well as DAT agents. The reasonable effective dose, together with the previously reported favorable characteristics for DAT imaging and quantification, indicates thatF-FE-PE2I is a suitable radioligand for DAT imaging.

EANM practice guideline/SNMMI procedure standard for dopaminergic imaging in Parkinsonian syndromes 1.0

“…The dosimetry of [ 18 F]FE-PE2I has been estimated in nonhuman primates and human subjects [146,147]. The estimated effective dose (ED) is 0.023 mSv/MBq, which is similar to that of other 18 F-labeled radioligands for brain imaging [148].…”

“…For the tracers described in this guideline, effective dose and absorbed dose (per MBq) to the highest exposed organs has been compiled from the available literature and is given in Table 4 [40,147,155,[163][164][165][166][167][168][169]. In most cases, following this guideline will lead to effective doses below 5 mSv per examination.…”

Reliability of dopamine transporter PET measurements with [18F]FE-PE2I in patients with Parkinson’s disease

“…[ 18 F]FE-PE2I, developed in 2009 [ 1 , 2 ], has, through several validity studies, proven to be a valuable positron emission tomography (PET) radioligand for dopamine transporter (DAT) imaging [ 1 – 8 ]. A clinical PET study with [ 18 F]FE-PE2I in twenty patients with early-stage PD showed an in vivo striato-nigral gradient of DAT loss [ 9 ], in agreement with post-mortem studies in patients and animal model studies [ 10 , 11 ].…”

Reliability of Dopamine Transporter PET Measurements with [18F]FE-PE2I in patients with Parkinson´s Disease

“…[ 18 F]FE-PE2I, developed in 2009 [1,2], has, through several validity studies, proven to be a valuable positron emission tomography (PET) radioligand for dopamine transporter (DAT) imaging [1][2][3][4][5][6][7][8]. A clinical PET study with [ 18 F]FE-PE2I in 20 patients with early-stage PD showed an in vivo striato-nigral gradient of DATloss [9], in agreement with post-mortem studies in patients, and animal model studies [10,11].…”