Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
EJNMMI Research
Published in: EJNMMI Research 1/2019

Open Access 01-12-2019 | Positron Emission Tomography | Original research

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

Authors: Bert-Ram Sah, Michael Sommerauer, Linjing Mu, Gloria Pla Gonzalez, Susanne Geistlich, Valerie Treyer, Roger Schibli, Alfred Buck, Geoffrey Warnock, Simon M. Ametamey

Published in: EJNMMI Research | Issue 1/2019

Login to get access

Abstract

Purpose

(E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone O-(3-(2-[18F]-fluoroethoxy)propyl) oxime ([18F]-PSS232) is a new PET tracer for imaging of metabotropic glutamate receptor subtype 5 (mGlu5), and has shown promising results in rodents and humans. The aim of this study was to estimate the radiation dosimetry and biodistribution in humans, to assess dose-limiting organs, and to demonstrate safety and tolerability of [18F]-PSS232 in healthy volunteers.

Methods

PET/CT scans of six healthy male volunteers (mean age 23.5 ± 1.7; 21–26 years) were obtained after intravenous administration of 243 ± 3 MBq of [18F]-PSS232. Serial whole-body (vertex to mid-thigh) PET scans were assessed at ten time points, up to 90 min after tracer injection. Calculation of tracer kinetics and cumulated organ activities were performed using PMOD 3.7 software. Dosimetry estimates were calculated using the OLINDA/EXM software.

Results

Injection of [18F]-PSS232 was safe and well tolerated. Organs with highest absorbed doses were the gallbladder wall (0.2295 mGy/MBq), liver (0.0547 mGy/MBq), and the small intestine (0.0643 mGy/MBq). Mean effective dose was 3.72 ± 0.12 mSv/volunteer (range 3.61–3.96 mSv; 0.0153 mSv/MBq).

Conclusion

[18F]-PSS232, a novel [18F]-labeled mGlu5 tracer, showed favorable dosimetry values. Additionally, the tracer was safe and well tolerated.
Literature
1.
Hess S, Blomberg BA, Zhu HJ, Hoilund-Carlsen PF, Alavi A. The pivotal role of FDG-PET/CT in modern medicine. Acad Radiol. 2014;21:232–49.CrossRef
2.
Taswell C, Villemagne VL, Yates P, Shimada H, Leyton CE, Ballard KJ, Piguet O, Burrell JR, Hodges JR, Rowe CC. 18F-FDG PET improves diagnosis in patients with focal-onset dementias. J Nucl Med. 2015;56:1547–53.CrossRef
3.
Nasrallah IM, Wolk DA. Multimodality imaging of Alzheimer disease and other neurodegenerative dementias. J Nucl Med. 2014;55:2003–11.CrossRef
4.
Galldiks N, Stoffels G, Ruge MI, Rapp M, Sabel M, Reifenberger G, Erdem Z, Shah NJ, Fink GR, Coenen HH, Langen KJ. Role of O-(2-18F-fluoroethyl)-L-tyrosine PET as a diagnostic tool for detection of malignant progression in patients with low-grade glioma. J Nucl Med. 2013;54:2046–54.CrossRef
5.
Schiepers C, Chen W, Cloughesy T, Dahlbom M, Huang SC. 18F-FDOPA kinetics in brain tumors. J Nucl Med. 2007;48:1651–61.CrossRef
6.
McGinnity CJ, Hammers A, Riano Barros DA, Luthra SK, Jones PA, Trigg W, Micallef C, Symms MR, Brooks DJ, Koepp MJ, Duncan JS. Initial evaluation of 18F-GE-179, a putative PET tracer for activated N-methyl D-aspartate receptors. J Nucl Med. 2014;55:423–30.CrossRef
7.
Sephton SM, Dennler P, Leutwiler DS, Mu L, Wanger-Baumann CA, Schibli R, Kramer SD, Ametamey SM. Synthesis, radiolabelling and in vitro and in vivo evaluation of a novel fluorinated ABP688 derivative for the PET imaging of metabotropic glutamate receptor subtype 5. Am J Nucl Med Mol Imaging. 2012;2:14–28.PubMed
8.
Sephton SM, Dennler P, Leutwiler DS, Mu L, Schibli R, Kramer SD, Ametamey SM. Development of [(18)F]-PSS223 as a PET tracer for imaging of metabotropic glutamate receptor subtype 5 (mGluR5). Chimia (Aarau). 2012;66:201–4.CrossRef
9.
Sephton SM, Herde AM, Mu L, Keller C, Rudisuhli S, Auberson Y, Schibli R, Kramer SD, Ametamey SM. Preclinical evaluation and test-retest studies of [(18)F]PSS232, a novel radioligand for targeting metabotropic glutamate receptor 5 (mGlu5). Eur J Nucl Med Mol Imaging. 2015;42:128–37.CrossRef
10.
Muller Herde A, Keller C, Milicevic Sephton S, Mu L, Schibli R, Ametamey SM, Kramer SD. Quantitative positron emission tomography of mGluR5 in rat brain with [(18) F]PSS232 at minimal invasiveness and reduced model complexity. J Neurochem. 2015;133:330–42.CrossRef
11.
Mizrahi R, Rusjan PM, Vitcu I, Ng A, Wilson AA, Houle S, Bloomfield PM. Whole body biodistribution and radiation dosimetry in humans of a new PET ligand, [(18)F]-FEPPA, to image translocator protein (18 kDa). Mol Imaging Biol. 2013;15:353–9.CrossRef
12.
Wanger-Baumann CA, Mu L, Honer M, Belli S, Alf MF, Schubiger PA, Kramer SD, Ametamey SM. In vitro and in vivo evaluation of [18F]-FDEGPECO as a PET tracer for imaging the metabotropic glutamate receptor subtype 5 (mGluR5). Neuroimage. 2011;56:984–91.CrossRef
13.
Kil KE, Zhu A, Zhang Z, Choi JK, Kura S, Gong C, Brownell AL. Development of [(123)I]IPEB and [(123)I]IMPEB as SPECT Radioligands for metabotropic glutamate receptor subtype 5. ACS Med Chem Lett. 2014;5:652–6.CrossRef
14.
Baumann CA, Mu L, Johannsen S, Honer M, Schubiger PA, Ametamey SM. Structure-activity relationships of fluorinated (E)-3-((6-methylpyridin-2-yl)ethynyl)cyclohex-2-enone-O-methyloxime (ABP688) derivatives and the discovery of a high affinity analogue as a potential candidate for imaging metabotropic glutamate recepors subtype 5 (mGluR5) with positron emission tomography (PET). J Med Chem. 2010;53:4009–17.CrossRef
15.
Honer M, Stoffel A, Kessler LJ, Schubiger PA, Ametamey SM. Radiolabeling and in vitro and in vivo evaluation of [18F]-FE-DABP688 as a PET radioligand for the metabotropic glutamate receptor subtype 5. Nucl Med Biol. 2007;34:973–80.CrossRef
16.
Treyer V, Streffer J, Ametamey SM, Bettio A, Blauenstein P, Schmidt M, Gasparini F, Fischer U, Hock C, Buck A. Radiation dosimetry and biodistribution of 11C-ABP688 measured in healthy volunteers. Eur J Nucl Med Mol Imaging. 2008;35:766–70.CrossRef
17.
Wong DF, Waterhouse R, Kuwabara H, Kim J, Brasic JR, Chamroonrat W, Stabins M, Holt DP, Dannals RF, Hamill TG, Mozley PD. 18F-FPEB, a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors: a first-in-human study of radiochemical safety, biokinetics, and radiation dosimetry. J Nucl Med. 2013;54:388–96.CrossRef
18.
Kessler RM, Seibyl J, Cowan RL, Zald D, Young JS, Ansari MS, Stabin MG. Radiation dosimetry of 18F-FPEB in humans. J Nucl Med. 2014;55:1119–21.CrossRef
19.
Ametamey SM, Treyer V, Streffer J, Wyss MT, Schmidt M, Blagoev M, Hintermann S, Auberson Y, Gasparini F, Fischer UC, Buck A. Human PET studies of metabotropic glutamate receptor subtype 5 with 11C-ABP688. J Nucl Med. 2007;48:247–52.PubMed
20.
DeGrado TR, Reiman RE, Price DT, Wang S, Coleman RE. Pharmacokinetics and radiation dosimetry of 18F-fluorocholine. J Nucl Med. 2002;43:92–6.
21.
Pauleit D, Floeth F, Herzog H, Hamacher K, Tellmann L, Muller HW, Coenen HH, Langen KJ. Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-L-tyrosine. Eur J Nucl Med Mol Imaging. 2003;30:519–24.CrossRef
Metadata
Title
Radiation dosimetry of [18F]-PSS232—a PET radioligand for imaging mGlu5 receptors in humans
Authors
Bert-Ram Sah
Michael Sommerauer
Linjing Mu
Gloria Pla Gonzalez
Susanne Geistlich
Valerie Treyer
Roger Schibli
Alfred Buck
Geoffrey Warnock
Simon M. Ametamey
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2019
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-019-0522-9

Other articles of this Issue 1/2019

EJNMMI Research 1/2019 Go to the issue

Original research

Impact of non-uniform attenuation correction in a dynamic [18F]-FDOPA brain PET/MRI study

Original research

Determination of a pharmacokinetic model for [11C]-acetate in brown adipose tissue

Original research

Prediction of the aggressiveness of non-functional pancreatic neuroendocrine tumors based on the dual-tracer PET/CT

Original research

Impact of the cerebrospinal fluid-mask algorithm on the diagnostic performance of 123I-Ioflupane SPECT: an investigation of parkinsonian syndromes

Original research

Interobserver variability of image-derived arterial blood SUV in whole-body FDG PET

Original research

A phase 0 study of the pharmacokinetics, biodistribution, and dosimetry of 188Re-liposome in patients with metastatic tumors