Development of a non-radiometric method for measuring the arterial input function of a 11C-labeled PET radiotracer

Shetty, Hitesh; Zoghbi, Sami S.; Morse, Cheryl L.; Kowalski, Aneta; Hirvonen, Jussi; Innis, Robert B.; Pike, Victor W.

doi:10.1038/s41598-020-73646-4

Cited by 3 publications

(4 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have earlier reported an LC–MS/MS method for measuring the constituent carbon-11 and carbon-13 isotopologues in 11 C-labeled tracer preparations as a basis for a nonradiometric method for measuring their molar activities . Subsequently, we extended this nonradiometric approach into the development of a method to measure the arterial input function for a 11 C-labeled tracer being used for PET on human subjects . In the method for measuring molar activity, the carrier M +1 isotopologue (carbon-13 isotopologue plus natural abundance of 2 H and 17 O isotopologues) was measured to avoid the possible saturation of the MS/MS detector with the far more abundant carrier carbon-12 isotopologue during the concurrent measurement of the carbon-11 isotopologue.…”

Section: Resultsmentioning

confidence: 99%

“…19 Subsequently, we extended this nonradiometric approach into the development of a method to measure the arterial input function for a 11 C-labeled tracer being used for PET on human subjects. 20 In the method for measuring molar activity, the carrier M+1 isotopologue (carbon-13 isotopologue plus natural abundance of 2 H and 17 O isotopologues) was measured to avoid the possible saturation of the MS/MS detector with the far more abundant carrier carbon-12 isotopologue during the concurrent measurement of the carbon-11 isotopologue. The LC−MS/MS peak area for carrier M+1 isotopologue was accurately transformed to that of carbon-12 isotopologue using a separately measured carrier M+1 to carbon-12 isotopologue ratio.…”

Section: Background and Approach To Lc−ms/ms Measurement Of Radioacti...mentioning

confidence: 99%

See 1 more Smart Citation

Tandem Mass Spectrometry as an Independent Method for Corroborating Fluorine-18 Radioactivity Measurements in Positron Emission Tomography

2022

Self Cite

View full text Add to dashboard Cite

Positron emission tomography (PET) uses many tracers labeled with fluorine-18 (t 1/2 = 109.8 min; β + 97%) for quantitative imaging of biochemical and physiological processes in animal and human subjects. In PET methodology, the radioactivity in a dose of an 18 F-labeled tracer to be administered to a living subject is measured with a calibrated ionization chamber. This type of detector measures the radioactivity of a sample relative to those of certified amounts of longer-lived surrogate isotopes that are recommended for detector calibration. No alternative means for corroborating widely varying fluorine-18 radioactivity measurements from calibrated ionization chambers has been available. Here, we describe an independent nonradiometric method for this purpose. In this method, highly sensitive liquid chromatography−tandem mass spectrometry (LC−MS/MS) is used to quantify the relative masses of the radioactive isotopologue ([ 18 F]1) and the accompanying nonradioactive counterpart (carrier 1) in an 18 F-labeled tracer preparation to give the mole ratio of [ 18 F]1. High-performance liquid chromatography (HPLC) with a mass-calibrated absorbance detection is used alongside to provide a separate measurement of the aggregate mass of all isotopologues. The radioactivity of the radiotracer is then derived in becquerels (Bq) from these two measurements, plus Avogadro's number and the decay constant of fluorine-18. For the chosen example [ 18 F]LSN3316612, the radioactivity values determined nonradiometrically and with a selected ionization chamber were in fair agreement. In addition, LC−MS/MS alone was found to provide an accurate measure of the half-life of fluorine-18.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Background and Approach To Lc−ms/ms Measurement Of Radioacti...mentioning

confidence: 99%

Tandem Mass Spectrometry as an Independent Method for Corroborating Fluorine-18 Radioactivity Measurements in Positron Emission Tomography

2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The physiological role of this protein remains enigmatic, especially considering recent data that suggest that, contrarily to rodents, humans do not overexpress TSPO transcripts and proteins in microglia of cases with Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis relative to controls [ 1 ]. Nevertheless, TSPO remains the most studied biomarker of neuroinflammation using positron emission tomography (PET) in neurologic [ 2 ] and psychiatric [ 3 ] disorders. The first PET radioligand for TSPO was [ 11 C]PK11195 [ 4 ], which suffered from low specific signal and high nonspecific binding [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of a novel 18F-labeled PET radioligand for translocator protein 18 kDa (TSPO) in monkey brain

Yan

Siméon

Liow

et al. 2023

Eur J Nucl Med Mol Imaging

Self Cite

View full text Add to dashboard Cite

Purpose [18F]SF51 was previously found to have high binding affinity and selectivity for 18 kDa translocator protein (TSPO) in mouse brain. This study sought to assess the ability of [18F]SF51 to quantify TSPO in rhesus monkey brain. Methods Positron emission tomography (PET) imaging was performed in monkey brain (n = 3) at baseline and after pre-blockade with the TSPO ligands PK11195 and PBR28. TSPO binding was calculated as total distribution volume corrected for free parent fraction in plasma (VT/fP) using a two-tissue compartment model. Receptor occupancy and nondisplaceable uptake were determined via Lassen plot. Binding potential (BPND) was calculated as the ratio of specific binding to nondisplaceable uptake. Time stability of VT was used as an indirect probe to detect radiometabolite accumulation in the brain. In vivo and ex vivo experiments were performed in mice to determine the distribution of the radioligand. Results After [18F]SF51 injection, the concentration of brain radioactivity peaked at 2.0 standardized uptake value (SUV) at ~ 10 min and declined to 30% of the peak at 180 min. VT/fP at baseline was generally high (203 ± 15 mL· cm−3) and decreased by ~ 90% after blockade with PK11195. BPND of the whole brain was 7.6 ± 4.3. VT values reached levels similar to terminal 180-min values by 100 min and remained relatively stable thereafter with excellent identifiability (standard errors < 5%), suggesting that no significant radiometabolites accumulated in the brain. Ex vivo experiments in mouse brain showed that 96% of radioactivity was parent. No significant uptake was observed in the skull, suggesting a lack of defluorination in vivo. Conclusion The results demonstrate that [18F]SF51 is an excellent radioligand that can quantify TSPO with a good ratio of specific to nondisplaceable uptake and has minimal radiometabolite accumulation in brain. Collectively, the results suggest that [18F]SF51 warrants further evaluation in humans.

show abstract

“…Brain in ammation upregulates 18 kDa translocator protein (TSPO), which is the most studied biomarker of neuroin ammation using positron emission tomography (PET) in neurologic [1] and psychiatric [2] disorders. The rst PET radioligand for TSPO was 11 C-PK11195 [3], which suffered from low speci c signal and high nonspeci c binding [4].…”

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of a novel 18F-labeled PET radioligand for translocator protein 18kDa (TSPO) in monkey brain

Yan¹,

Siméon

Liow

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Purpose: 18F-SF51 was previously found to have high binding affinity and selectivity for 18kDa translocator protein (TSPO) in mouse brain. This study sought to further evaluate the suitability of 18F-SF51 for absolute quantification of TSPO in monkey brain. Methods: Positron emission tomography (PET) imaging was performed in monkey brain (n=3) at baseline and after pre-blockade with the TSPO ligands PK11195 and PBR28. TSPO binding was calculated as total distribution volume corrected for free parent fraction in plasma (VT/fP) using a two-tissue compartment model. Receptor occupancy and nondisplaceable uptake were determined via Lassen plot. Binding potential (BPND) was calculated as the ratio of specific binding to nondisplaceable uptake. Time stability of VT was used as an indirect probe to detect radiometabolite accumulation in the brain. In vivo and ex vivo experiments were performed in mice to determine the distribution of the radioligand. Results: After 18F-SF51 injection, the concentration of brain radioactivity peaked at 2.0 standardized uptake value (SUV) at ~10 minutes and declined to 30% of the peak at 180 minutes. VT/fP at baseline was generally high (203±15 mL· cm-3) and decreased by ~90% after blockade with PK11195. BPND of the whole brain was 7.6 ± 4.3. VT values reached levels similar to terminal 180-minute values by 70 minutes and remained relatively stable thereafter with excellent identifiability (standard errors < 5%), suggesting that no significant radiometabolites accumulated in the brain. Ex vivo experiments in mouse brain showed that 96% of radioactivity was parent. No significant uptake was observed in the skull, suggesting a lack of defluorination in vivo. Conclusion: The results demonstrate that 18F-SF51 is an excellent radioligand with a good ratio of specific to nondisplaceable uptake as well as good time stability of total receptor binding. Collectively, the results suggest that 18F-SF51 warrants further evaluation in humans.

show abstract

Development of a non-radiometric method for measuring the arterial input function of a 11C-labeled PET radiotracer

Cited by 3 publications

References 26 publications

Tandem Mass Spectrometry as an Independent Method for Corroborating Fluorine-18 Radioactivity Measurements in Positron Emission Tomography

Tandem Mass Spectrometry as an Independent Method for Corroborating Fluorine-18 Radioactivity Measurements in Positron Emission Tomography

In vivo evaluation of a novel 18F-labeled PET radioligand for translocator protein 18 kDa (TSPO) in monkey brain

In vivo evaluation of a novel 18F-labeled PET radioligand for translocator protein 18kDa (TSPO) in monkey brain

Contact Info

Product

Resources

About