Radiation Dosimetry of¹⁸F-FPEB in Humans

Abstract

18 F-3-fluoro-5- [(pyridin-3-yl)ethynyl]benzonitrile ( 18 F-FPEB) is a potent and specific radioligand for the metabotropic glutamate receptor subtype 5 (mGluR5). Before undertaking clinical research studies with 18 F-FPEB, we performed studies of human radiation dosimetry. Methods: Serial whole-body scans were obtained in 9 healthy human subjects (5 men, 4 women) for 190-440 min after the intravenous administration of 18 F-FPEB. Radiation doses were estimated using the OLINDA/EXM software. Results: Peak organ doses were to the urinary bladder wall, 0.258 mGy/MBq (0.955 rad/mCi), and gallbladder wall, 0.193 mGy/MBq (0.716 rad/mCi). The effective dose was 0.025 mSv/MBq (0.0922 rem/mCi). The doses to the red marrow and spleen were 0.00797 mGy/MBq (0.0295 rad/mCi) and 0.00709 mGy/ MBq (0.0262 rad/mCi), respectively. Reducing the urinary voiding interval to 60 or 90 min lowered the urinary bladder wall dose to 0.0885 mGy/MBq (0.327 rad/mCi) or 0.128 mGy/MBq (0.473 rad/ mCi), respectively, and the effective dose to 0.0149 mSv/MBq (0.0551 rem/mCi) or 0.0171 mSv/MBq (0.0634 rem/mCi), respectively. Conclusion: Urinary voiding should be performed during 18 F-FPEB studies to minimize radiation exposure to research subjects. The metabotropic glutamate receptor subtype 5 (mGluR5) is a type I metabotropic glutamatergic receptor, which is an important modulator of both N-methyl-D-aspartate and dopamine receptor signaling; it positively modulates N-methyl-D-aspartate receptor function and has complex interactions with dopamine receptor intracellular signaling (1,2). Altered function of the mGluR5 has been implicated in the pathophysiology of several neurologic and psychiatric disorders including Fragile X syndrome (3), Huntington and Parkinson disease (4,5), psychostimulant drug and alcohol abuse (6-8), depression, and anxiety as well as being involved in learning and memory (9-12). 18 F-3-fluoro-5-[(pyridin-3-yl)ethynyl] benzonitrile ( 18 F-FPEB) is a promising radioligand for imaging the mGluR5 in humans. It has a high affinity (0.11-0.15 nM) for the mGluR5 and nearly optimal lipophilicity for imaging, with a logP of 2.8 (13). Initial human imaging studies have shown high contrast between regions rich in mGluR5 levels, such as the anterior cingulated, and regions with low levels, such as the cerebellum and pons, as well as the ability to estimate regional receptor levels using both bolus administration with 2-tissue-compartment modeling and bolus-infusion administration (14,15). Given the importance of the mGluR5 in several disease states and its promise as a PET radioligand for studies of mGluR5, we undertook studies of human radiation dosimetry of 18 F-FPEB. MATERIALS AND METHODSAfter approval of this study by the appropriate institutional review boards (IRBs), all subjects provided written informed consent before enrollment. All subjects had to be 18 y or older and have a normal medical history, physical examination, and laboratory testing including a comprehensive metabolic panel, complete blood panel with differential, ...

Radiation dosimetry of [18F]-PSS232—a PET radioligand for imaging mGlu5 receptors in humans

“…Cumulated organ activity of the gall bladder might be overestimated, and of the large bowel underestimated, because it can be expected that tracer is cleared from small to large bowel within hours (Table 4 for results using ICRP 30 gastrointestinal model). Beyond that, organ doses in our study are in the same range as other lipophilic tracers [18]. The dosimetry results for [ 18 F]-PSS232 confirmed a low radiation dose to the urinary system (Table 3).…”

Amyloid pathology induces dysfunction of systemic neurotransmission in aged APPswe/PS2 mice

“…According to the Radioactive Drug Research Committee guidelines in the United States, the effective dose for the whole body should not exceed 30 or 50 mSv/year (FDA 21 CFR 361.1). Previous studies have reported that the whole-body effect dose of PET scans used in the present study was 0.015-0.021 mSv/MBq (mean 0.018 mSv/MBq, Van Laere et al, 2010;Kessler et al, 2014;Sabri et al, 2015;Srinivasan et al, 2020). For an injected dose of 370 MBq, the whole-body was 6.68 mSv/each and 33.4 mSv/five study.…”

Fragile X Mental Retardation Protein and Cerebral Expression of Metabotropic Glutamate Receptor Subtype 5 in Men with Fragile X Syndrome: A Pilot Study

“…Clinical trials of mGluR 5 NAMs for FXS were limited by the variable age groups of study participants, problematic outcome measurements, placebo effects, and potentially the absence of a tool to measure the expression of mGluR 5 in the living brains of participants with FXS [2,[42][43][44]46,56,57]. Our finding that mGluR 5 expression measured by positron emission tomography (PET) with 3-[ 18 F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([ 18 F]FPEB), a potent and safe specific mGluR 5 inhibitor (Figures 1 and 2) [58,59], is re-duced in all brain regions in men with FXS [2] compared to participants of both sexes with ASD and TD [2,42,[60][61][62], was confirmed utilizing positron emission tomography and magnetic resonance (PET/MR) imaging on an unmedicated cohort of older men with FXS and age-and sex-matched participants with TD suggesting that the current protocol may be a valuable biomarker for mGluR 5 expression in clinical trials of novel agents for humans with FXS and other subtypes of ASD [63]. We showed that [ 18 F]FPEB may be a promising tool to obtain quantitative measurements of mGluR 5 expression in individuals with FXS for clinical trials and other investigations [2,42,[64][65][66][67].…”