First-in-Human PET Imaging of [<sup>18</sup>F]SDM-4MP3: A Cautionary Tale

Desmond, Kimberly L.; Lindberg, Anton; Garcia, Armando; Tong, Junchao; Harkness, Michael B.; Dobrota, Elena; Smart, Kelly; Uribe, Carme; Meyer, Jeffrey H.; Houle, Sylvain; Strafella, Antonio P.; Li, Songye; Huang, Yiyun; Vasdev, Neil

doi:10.1155/2023/8826977

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…[ 18 F]SynVesT-1 was synthesized as previously described [10], with minor modifications [16]. PET scans were acquired on a GE Discovery 5-ring PET/ CT scanner.…”

Section: Image Acquisitionmentioning

confidence: 99%

Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [¹⁸F]SynVesT-1 PET in Parkinson’s Disease

Smart,

Uribe,

Desmond

et al. 2023

Mol Imaging

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Synaptic density in the central nervous system can be measured in vivo using PET with [18F]SynVesT-1. While [18F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson’s disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [18F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [18F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential ( B P ND ) using centrum semiovale (CS) as a reference region. The SRTM2 method was used with k 2 ′ fixed to either a sample average value (0.037 min-1) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux ( p s > 0.47 ). Each fitting method produced B P ND estimates in close agreement with those derived from the 1TCM (subject R 2 s > 0.98 , bias < 10 % ), with no difference in bias between the control and PD groups. With SRTM2, B P ND estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans ( bias < 6 % ). While these are preliminary results from a small sample of patients with PD ( n = 5 ), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [18F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.

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“…[ 18 F]SynVesT-1 was synthesized as previously described [10], with minor modifications [16]. PET scans were acquired on a GE Discovery 5-ring PET/ CT scanner.…”

Section: Image Acquisitionmentioning

confidence: 99%

Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [¹⁸F]SynVesT-1 PET in Parkinson’s Disease

Smart,

Uribe,

Desmond

et al. 2023

Mol Imaging

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In vitro evaluation of PET radiotracers for imaging synaptic density, the acetylcholine transporter, AMPA-tarp-γ8 and muscarinic M4 receptors in Alzheimer’s disease

d’Orchymont

2024

Am J Nucl Med Mol Imaging

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Several therapeutics and biomarkers that target Alzheimer's disease (AD) are under development. Our clinical positron emission tomography (PET) research programs are interested in six radiopharmaceuticals to image patients with AD and related dementias, specifically [ 11 C]UCB-J and [ 18 F]SynVesT-1 for synaptic vesicle glycoprotein 2A as a marker of synaptic density, two vesicular acetylcholine transporter PET radiotracers: [ 18 F]FEOBV and [ 18 F]VAT, as well as the transmembrane AMPA receptor regulatory protein (TARP)-γ8 tracer, [ 18 F]JNJ-64511070, and the muscarinic acetylcholine receptor (mAChR) M4 tracer [ 11 C]MK-6884. The goal of this study was to compare all six radiotracers (labeled with tritium or 18 F) by measuring their density variability in pathologically diagnosed cases of AD, mild cognitive impairment (MCI) and normal healthy volunteer (NHV) human brains, using thin-section in vitro autoradiography (ARG). Region of interest analysis was used to quantify radioli gand binding density and determine whether the radioligands provide a signal-to-noise ratio optimal for showing changes in binding. Our preliminary study confirmed that all six radiotracers show specific binding in MCI and AD. An expected decrease in their respective target density in human AD hippocampus tissues compared to NHV was observed with [ 3 H]UCB-J, [ 3 H]SynVesT-1, [ 3 H]JNJ-64511070, and [ 3 H]MK-6884. This preliminary study will be used to guide human PET imaging of SV2A, TARP-γ8 and the mAChR M4 subtype for imaging in AD and related dementias.

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First-in-Human PET Imaging of [¹⁸F]SDM-4MP3: A Cautionary Tale

Cited by 2 publications

References 28 publications

Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [¹⁸F]SynVesT-1 PET in Parkinson’s Disease

Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [¹⁸F]SynVesT-1 PET in Parkinson’s Disease

In vitro evaluation of PET radiotracers for imaging synaptic density, the acetylcholine transporter, AMPA-tarp-γ8 and muscarinic M4 receptors in Alzheimer’s disease

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First-in-Human PET Imaging of [18F]SDM-4MP3: A Cautionary Tale

Cited by 2 publications

References 28 publications

Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [18F]SynVesT-1 PET in Parkinson’s Disease

Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [18F]SynVesT-1 PET in Parkinson’s Disease

In vitro evaluation of PET radiotracers for imaging synaptic density, the acetylcholine transporter, AMPA-tarp-γ8 and muscarinic M4 receptors in Alzheimer’s disease

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First-in-Human PET Imaging of [¹⁸F]SDM-4MP3: A Cautionary Tale

Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [¹⁸F]SynVesT-1 PET in Parkinson’s Disease

Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [¹⁸F]SynVesT-1 PET in Parkinson’s Disease