Visual Abstract
Abstract
Although the alteration of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) distribution is believed to underlie physiologic and pathologic neuronal function, there has been no modality to evaluate AMPARs in a living human. [11C]K-2, the PET tracer we previously developed, is the first and only technology, to the best of our knowledge, to visualize AMPAR densities in the living human brain. Despite its favorable kinetics as a PET tracer, the short half-life of 11C limits the potential of [11C]K-2. We recently developed an 18F-labeled PET tracer, [18F]K-40, which demonstrated AMPAR-specific binding properties and brain distribution similar to that of [11C]K-2 in preclinical studies. The purpose of this first-in-human study is to evaluate the properties of [18F]K-40 in humans and to compare the kinetics and PET images of [18F]K-40 with those of [11C]K-2. Methods: Five healthy volunteers were enrolled and underwent dynamic PET imaging using [18F]K-40 and [11C]K-2. The nondisplaceable binding potential (BPND) with white matter as the reference was calculated by Logan graphical analysis using tissue time–activity curves (TACs), and the total distribution volume of [18F]K-40 was calculated using plasma TACs. The intraindividual correlation between BPND values obtained for [18F]K-40 and [11C]K-2 was examined. To optimize the time window for PET scanning, BPND and SUV ratio were evaluated. Results: The tissue TACs of [18F]K-40 showed curves similar to those of [11C]K-2. Logan graphical analysis using plasma TACs revealed reversible binding of [18F]K-40. The BPND obtained with [18F]K-40 and [11C]K-2 significantly correlated in each corresponding region and showed very good correlation, which indicated that K-40, as observed with K-2, can provide PET images that reflect the amount of AMPARs. A good linear relationship was observed between BPND and the summation image of SUV ratios between 40 and 50 min after radiotracer injection. Conclusion: [18F]K-40, as with [11C]K-2, has favorable binding properties as an AMPAR PET tracer. Thus, [18F]K-40 could characterize AMPAR distribution in pathophysiologic conditions of the brain and facilitate the development of novel diagnostics of neuropsychiatric disorders.
Glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are a subtype of glutamate receptors and play a pivotal role in neuronal excitatory synaptic transmission (1–8). Many animal studies have suggested that changes in the number of synaptic AMPARs underlie physiologic function, including learning and memory (1–8). Furthermore, aberrant distribution and malfunction of AMPARs are thought to underlie neuropsychiatric disorders, such as epilepsy, dementia, schizophrenia (9–11). Despite numerous animal and postmortem studies suggesting the potential of AMPARs as diagnostic and therapeutic targets for neuropsychiatric disorders, the clinical translation has been limited. This could be attributed to the lack of a modality for AMPAR quantification in the living human brain, as the trafficking of AMPARs is activity-dependent, which is difficult to characterize with postmortem brain studies.
PET is a nuclear medicine imaging modality widely used in clinical diagnosis. Despite the development of many AMPAR-targeted PET probes, the development of a practical PET probe with balanced functions of brain uptake, AMPAR-binding ability, and blood clearance poses a challenge (12–17).
A PET probe, [11C]K-2, that successfully visualizes cell-surface AMPARs in the living human brain (18–20), was used to quantify AMPAR densities in patients with 4 major psychiatric disorders, including schizophrenia, bipolar disorder, depression, and autism spectrum disorder (21), and demonstrated strong significant correlations between AMPAR density in specific brain areas and the symptomatology scores for each psychiatric disorder (21). Some brain areas showed significant differences in AMPAR density in patients with each psychiatric disorder compared with healthy subjects (21). Some of these overlapped across diseases, indicating that these areas are commonly affected regions of the brain throughout psychiatric disorders (21).
In patients with focal epilepsy, the amplitude of abnormal γ-activity was positively correlated with regional AMPAR density. Meanwhile, AMPAR densities in some regions were significantly lower compared with healthy subjects, suggesting that Hebbian plasticity and homeostatic scaling regulate epileptic brain function (22).
These results indicate that [11C]K-2 has sufficient potential to elucidate the physiologic and pathologic alterations of AMPAR density in the human brain. However, the short half-life (20 min) of the radioisotope 11C necessitates immediate postproduction administration of [11C]K-2 that warrants an on-site cyclotron. Therefore, the development of a new tracer labeled with a radioisotope with a longer half-life is desirable.
The radioisotope 18F has a longer half-life (∼110 min), and recently, we attempted the development of an 18F-labeled AMPAR PET probe.
For screening of the 18F-labeled AMPAR PET probe, the candidate compounds were synthesized on the basis of the structures of [11C]K-2, which has been previously established as an AMPAR PET tracer. The AMPAR PET suitability of the candidate compounds was evaluated by small-animal PET imaging and comparison with K-2. For the candidate compounds that provided favorable images, specificity was evaluated using rats in which the AMPAR was knocked down by short hairpin RNA technology, and K-40 was ultimately identified as the most promising compound (23).
In this clinical study, we performed both [11C]K-2 and [18F]K-40 PET scans on the same subjects to investigate the applicability of [18F]K-40 as an AMPAR PET tracer.
MATERIALS AND METHODS
Ethics Statement
The clinical study protocol was approved by Yokohama City University Human Investigation Committee in accordance with the ethical guidelines for medical and health research involving human subjects issued by the Japan Ministry of Health, Labor, and Welfare, and the study was registered (ID: jRCTs031220226). The date of the first and last treatment was September 26, 2022, and December 5, 2022, respectively. All subjects provided written informed consent.
Radiosynthesis of [18F]K-40 and [11C]K-2
[18F]K-40 and [11C]K-2 were synthesized as described previously (20,23). The specifications for [18F]K-40 and [11C]K-2 injection were set as described in Tables 1 and 2. All materials were tested for each production run. As an exception, the sterility test results were confirmed 2 wk after production and injection.
Specification of [18F]K-40
Specification of [11C]K-2
In Vitro Binding Assay
Binding affinity assays of K-40OH for AMPARs were performed as previously described (20). In vitro binding selectivity assays were performed by Sekisui Medical to examine the ability of K-40OH to interact with various receptors and channels (off-target binding assay at a concentration of 10 μM; study AL-8801). Details are described in the supplemental materials (available at http://jnm.snmjournals.org).
Human Subjects
A sample size of 5 was set, and only men were included under ethical consideration. The eligible subjects were individuals aged 20–39 y without any history of neuropsychiatric disorders and had sufficient discriminatory ability to provide consent, according to the MacArthur Competence Assessment Tool for Treatment. No subject had any current mental disorders, based on the criteria in the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, DSM-IV, DSM-5, and ICD10 (24–26). The inclusion and exclusion criteria are provided in the supplemental materials.
A total of 5 healthy subjects met the eligibility criteria and were registered (5 men; age, 25.8 ± 7.5 y). Each subject underwent MRI, PET with [18F]K-40, and arterial blood sampling. [11C]K-2 PET scanning was performed 2–4 wk after [18F]K-40 PET scanning. All tests were performed at Yokohama City University Hospital.
In Vivo PET and MRI
[18F]K-40 and [11C]K-2 were synthesized at Yokohama City University Hospital in accordance with the good manufacturing practices ordinance and certified by the Japanese Society of Nuclear Medicine. PET imaging was performed around 2:00 to 4:00 pm using a Discovery MI scanner (GE HealthCare). MRI was performed on a GE Discovery MR750 (GE HealthCare). Details of PET and MRI were described in supplemental materials.
Measurement of Arterial Contents of Unmetabolized and Metabolized [18F]K-40
During the [18F]K-40 scans, arterial blood sampling was performed to analyze the unmetabolized and metabolized fractions at 1.5, 3, 7, 12, 20, 30, and 60 min after radiotracer injection. Blood samples were centrifuged at 1,500 g for 5 min at 4°C, and the supernatant was collected as the plasma fraction. Subsequently, 0.1% trifluoroacetic acid in a 2:1 (v/v) mixture of acetonitrile and water was added to the plasma, followed by centrifugation at 15,000 g for 10 min. To measure the unmetabolized and metabolized [18F]K-40 components, the supernatant was filtered off and then analyzed by radio–high-performance liquid chromatography, using a combination of a 1260 Infinity II LC system (Agilent) with a COSMOSIL πNAP packed column (5 μm, 10-mm inner diameter × 250 mm; Nacalai Tesque) and a FlowCountPRO with a bismuth germanate detector flow-scintillation analyzer (Eckert & Ziegler). The mobile phase consisted of 0.1% trifluoroacetic acid in a 55:45 (v/v) mixture of acetonitrile and water (flow rate, 4 mL/min). Finally, the ratio of unmetabolized to metabolized [18F]K-40 was calculated.
PET Imaging Analysis
PET images and T1-weighted MR images were normalized to Montreal Neurological Institute space using the PMOD PNEURO tool version 3.7 (PMOD Technologies) to facilitate use of the N30R83 atlas. The volumes of interest were automatically obtained using the most likely localization of the brain areas encoded in the N30R83 maximum-probability atlas (27). The volume of interest of the white matter, which was the reference region, was obtained using the original script (20). The tissue time–activity curves (tTACs) were then generated for these regions.
Logan Graphical Analysis (LGA)
LGA was applied to compute nondisplaceable binding potential (BPND) and produce the images (28,29). The BPND is a quantitative unitless index of receptor density that is defined as the ratio of the amount of available receptor sites to the disassociation rate between an administered radiopharmaceutical and its specific binding sites (30). As LGA is implemented as a linear regression, stable and fast computation is expected and is applicable to any compartment model, such as the 1-tissue–2-compartment or 2-tissue–3-compartment model. If the kinetics of the administered radioligand exhibit reversible behavior, we can compute BPND using LGA. Therefore, they are commonly used in PET receptor imaging. The tTAC in the reference region, a white matter region, was given to the LGA. The beginning of the linear regression is 20 min after administration. The total distribution volume (VT) is computed using the metabolite-unadjusted plasma time–activity curve (pTAC) and tTAC (Eq. 1 of (31)) because both the parent and metabolite fractions can enter the brain tissue via the blood–brain barrier.
Optimal Scan Protocol for SUV Ratio (SUVR) Representing AMPAR Density
We searched an optimal scan protocol to acquire SUVR images that represent the AMPAR density. The acquired dynamic data were interpolated to compute the PET values at any time, and then SUVRs were computed. The scan start time varied from 10 to 70 min after administration, and the frame widths were investigated from 5 to 20 min. These computed SUVR was compared with BPND.
Statistical Analysis
Statistical analyses were conducted in GraphPad Prism 10 (GraphPad Software), and the data are expressed as mean ± SD, unless indicated otherwise. Correlation coefficients were calculated using Pearson correlation analysis. The results are displayed as r2 values. Statistical significance was set at a P value of less than 0.05. Detailed statistical information for each experiment is provided in the corresponding figure legends.
RESULTS
Safety
Five healthy subjects underwent a PET scan with [18F]K-40 (Fig. 1) and [11C]K-2. The mean administration doses of [18F]K-40 and [11C]K-2 were 186 ± 7 MBq (range, 176–193 MBq) and 378 ± 8 MBq (range, 365–387 MBq), respectively. No significant alterations from baseline biochemistry, hematology, or urine laboratory values were noted, and no significant adverse events were observed during the 7-d observation period after the administration of [18F]K-40.
Chemical structures of [18F]K-40, [18F]K-40OH, [11C]K-2, and [11C]K-2OH.
Plasma Metabolites
Only one metabolite of [18F]K-40 was detected in the blood: [18F]K-40OH (Supplemental Fig. 1), which was formed by the hydrolysis of the terminal amide group to a carboxyl group, similarly as the previously reported AMPAR PET drug, [11C]K-2, is metabolized to [11C]K-2OH (Fig. 1) (18,20). The structure of the metabolite K-40OH was identified using the retention time of high-performance liquid chromatography, which matched that of a separately synthesized standard of K-40OH (Supplemental Fig. 1). Chemical structures of [18F]K-40, [18F]K-40OH, [11C]K-2, and [11C]K-2OH are shown in Figure 1.
pTAC Analysis
Analysis of the radioactivity and metabolites in the plasma obtained from arterial blood samplings after [18F]K-40 administration showed that plasma radiation levels increased sharply immediately after administration, quickly decreased to a low level, and decreased gradually thereafter. Figure 2A shows the mean pTAC and the parent and metabolite fractions of K-40, which was metabolized to K-40OH immediately after administration. Half of the K-40 was metabolized 3 min after administration and was almost all completely metabolized 10 min later. Figure 2B shows the mean pTAC and parent and metabolite fractions of [11C]K-2, which show similarities in the kinetics of K-40 and K-2 in humans. The detailed plasma time activities of [11C]K-2, [18F]K-40, and each metabolite are shown in Supplemental Figure 2.
Averaged pTAC (left panels) and metabolic rate (right panels) of [18F]K-40 and [11C]K-2. Studies for [18F]K-40 (n = 5) (A). Studies for [11C]K-2 (n = 6) (B). Data in (B) were obtained from previous study (20). Data are shown as mean ± SD.
tTAC Analysis
The subject’s brain was divided into several volumes of interest, and Figure 3A shows a graph of the time course of radioactivity in each volume of interest based on dynamic PET imaging data using [18F]K-40. This tTAC shows rapid radiotracer uptake in the brain and regional heterogeneities, with the lowest radioactivity in white matter, in which no AMPARs were detected previously (20).
(A) Averaged time–activity curve in brain regions of healthy subjects injected with [18F]K-40 (n = 5). (B) Typical LGA plots. Estimated amount of K-40 and K-40OH was integrated in left panel, and estimated amount of K-40OH was integrated in right panel. Data are shown as mean ± SD. C and Cp are time–activity curves in tissue and arterial plasma. Cp is combined radioactivity of K-40 and K-40OH (B, left) and radioactivity of K-40OH (B, right).
LGA
LGA was performed using the plasma and tissue radioactivity concentrations obtained from the PET images. Figure 3B shows the typical LGA plots of a representative subject. As K-40 in the blood is rapidly metabolized to K-40OH, 2 types of LGA were performed: Figure 3B left, using the radioactivity value in plasma that combines the parent substance (K-40) and metabolite (K-40OH), and Figure 3B right, using only the radioactivity of the metabolite. In either case, the LGA showed a good linear relationship in all brain regions, indicating that this PET drug reached a reversible equilibrium state between binding to AMPARs and plasma. Further, these 2 LGA exhibited almost identical slopes, suggesting that [18F]K-40OH constitutes AMPAR PET image after the [18F]K-40 injection.
Affinity and Selectivity of K-40OH for AMPARs
Since [18F]K-40OH constitutes an AMPAR PET image after the [18F]K-40 injection, we focused on K-40OH for further in vitro analysis. To analyze the binding property of K-40OH for AMPARs, autoradiography was performed with [18F]K-40OH. The binding affinity (measured by the dissociation constant) was 19.5 nM, and the binding capacity was 21.9 fmol/mg of tissue (Supplemental Fig. 3). These are within the same range as those of K-2OH (20). In an off-target binding assay, K-40OH showed no marked binding to any major receptors in the central nervous system other than AMPARs (Supplemental Table 1).
VT with pTAC and BPND Using White Matter as Reference
VT of various brain regions was calculated with pTACs. VT is determined by the ratio of ligand concentration in tissue to the concentration in plasma and is an index representing the extent to which a drug has migrated into the tissue (Fig. 4A) (30). Among the brain regions, we found the smallest VT for white matter in [18F]K-40. These results suggest that the white matter is applicable as a reference region for K-40 to quantify AMPAR density. White matter is an area in which no AMPARs are present and can be considered a good reference area for AMPAR PET images using [11C]K-2 (19,20,22).
(A) VT values of various brain regions computed with pTAC from LGA plots in [18F]K-40 PET study. (B) BPND values of various brain regions calculated with Logan plot analysis using white matter as reference region (without pTAC). (C) Linear regression analysis between VT of brain regions (except white matter) computed with pTAC and BPND using white matter as reference. (D) Comparison of VT value, which corresponds to zero point of BPND, using white matter as reference (x intercept of plot in (C)) and VT of white matter computed with pTAC. n = 5. (A and B) Data are shown as mean ± SD. HC = healthy control.
Binding potential is a quantitative index of receptor density used in PET receptor imaging and is defined as the ratio of apparent binding capacity and dissociation constant (30). The BPND value for each tissue was calculated using LGA without pTAC, with the white matter as the reference region (Fig. 4B). We then plotted the relationship between VT and BPND in Figures 4A and 4B, except for white matter (Fig. 4C). VT values, which corresponded to the zero point of BPND when using white matter as a reference (x intercept of the plot in Fig. 4C), were almost identical to the VT values computed for white matter when using the pTAC (Fig. 4D). These results, in combination with the biochemical study showing no AMPAR expression in white matter (20), suggested that calculating BPND with LGA using white matter as the reference was feasible for [18F]K-40, and the applied algorithm to compute BPND of LGA is reasonable.
PET Imaging of [18F]K-40 and [11C]K-2
One subject underwent AMPAR PET imaging with both of [18F]K-40 and [11C]K-2, and the computed BPND images of [18F]K-40 and [11C]K-2 were compared. Figure 5A shows that BPND images in each case represented similar regional distributions, with a very good correlation between the BPND values of [18F]K-40 and [11C]K-2 of each region (Fig. 5B). The linear relationship between BPND of [18F]K-40 and [11C]K-2 for 5 subjects on average was y = 0.75x + 0.18 (R2 = 0.85). The variation in slope between subjects was sufficiently small, and the y-intercept was also sufficiently small compared with the BPND value. These results suggest that [18F]K-40 can be used as an AMPAR PET tracer with a half-life longer than that of [11C]K-2.
(A) Comparison between [11C]K-2 BPND PET images and [18F]K-40 BPND PET images. (B) Correlation between [11C]K-2 and [18F]K-40 BPND values in brain regions in healthy subjects. HC = healthy control.
Optimization of Time Frame for [18F]K-40 PET Imaging
For clinical use, using Bland–Altman plots, we explored the time frame showing the best correlation between BPND and SUVR.
The time frame showing the best correlation between BPND and SUVR, with white matter as a reference, was examined. The tTAC time frame was seamlessly supplemented, and an SUVR-based Bland–Altman analysis was performed by calculating the data accumulated for 10 min from x min after administration, with BPND, which used the white matter as the reference region. The difference between SUVR−1 and BPND was plotted against the start of the scan (Fig. 6A). The smallest difference between SUVR−1 and BPND was observed approximately 45 min after administration. The limit of agreement, which is defined as a 95% CI of the difference and describes the stability of the difference between BPND and SUVR−1, is adequately small in the 10-min time frame from 30 to 55 min after administration. On the basis of these results, we found that BPND and SUVR from 40 to 50 min after administration were highly correlated (Fig. 6B). Averaged across all subjects, the linear relationship between SUVR40–50min−1 and BPND was represented as y = 1.00x – 0.01 (R2 = 0.98). Figure 6C shows the BPND and SUVR images of each subject, and they are highly identical. Thus, the SUVR at 40–50 min is an appropriate surrogate outcome measure for AMPAR density.
(A) Change in limit of agreement on difference in BPND and SUVR with varying scan start time wherein frame width is fixed at 10 min. (B) Correlation between BPND value and SUVR40–50min−1 in brain regions in healthy subjects. (C) Comparison between [18F]K-40 BPND PET images and [18F]K-40 SUVR PET images at 40–50 min.
DISCUSSION
[11C]K-2 is the world’s first AMPAR PET tracer, and its 18F-labeled tracer, K-40, was investigated in humans in this study. We have already confirmed from various angles that [11C]K-2 AMPAR PET images reflect the amount of AMPARs in the brain (18,20). K-2 is quickly metabolized to a carboxylic acid form in both the brain and blood. In an early-phase after the intravenous injection of [11C]K-2, a substantial amount of K-2 crosses the blood–brain barrier and is quickly metabolized. Only the metabolite K-2OH remains in both the brain and blood and reaches equilibrium. These kinetics, as well as our previous in vitro experiments, proved that [11C]K-2 represents cell-surface AMPARs, a physiologically crucial fraction (18,20).
This study revealed that K-40 also has similar characteristics. As obtained in previous studies, the blood concentration of K-2 decreased rapidly after administration and gradually decreased from 10 to 20 kBq/mL (Fig. 2B). Approximately half of K-2 was metabolized about 3 min after administration, and it was almost completely metabolized within 10 min (Fig. 2B). In comparison, K-40 was metabolized slightly faster than K-2, albeit with the same kinetics (Figs. 2A and 2B).
As shown in Figure 3B, K-40, as observed with K-2, showed a good linear relationship with LGA, indicating a reversible equilibrium state. Even when the amount of ligand in the blood was corrected with K-40OH and LGA was performed with the metabolite (K-40OH), a good linear relationship was also obtained (Fig. 3B). This indicated that K-40 was quickly metabolized to K-40OH after administration and reached equilibrium with the metabolite. These kinetic characteristics are important features of this PET drug. Previous research has shown that the unchanged K-2 has sufficient blood–brain barrier permeability, but the metabolite K-2OH has slower permeability through the blood–brain barrier and no permeability through cell membranes (18). Therefore, the unchanged K-40 ligand enters the brain immediately after administration and is quickly metabolized, which slows its excretion from the brain and creates an equilibrium state long enough for PET imaging. Furthermore, these results suggest that PET images with the injection of [18F]K-40 also represent cell-surface AMPARs, as we observed with [11C]K-2. Further in vitro studies are required to confirm this potential property of [18F]K-40.
We previously proved that white matter is the appropriate reference region for [11C]K-2, since biochemical analysis with resected tissues of patients with refractory epilepsy revealed that there were no AMPAR in the white matter and that the nondisplaceable volume in brain regions other than the white matter was almost equivalent to the VT of the white matter (20), which was the smallest in the brain. The same property was demonstrated in the current study, which proved that white matter is also an appropriate reference region for [18F]K-40 images. In addition, we found a good correlation between BPND of [11C]K-2 and that of [18F]K-40 images, with white matter as a reference (Fig. 5), demonstrating that the [18F]K-40 image also represents AMPAR density.
In AMPAR PET imaging using [18F]K-40, SUVR using a time frame of 40–50 min after administration provided the best correlation with BPND. The 10-min scan 40 min after administration is useful for clinical practice. The excellent correlation between the SUVR and BPND constitutes an excellent performance feature of this PET drug. The best correlation between SUVR and BPND was observed around 40–50 min, although the difference between SUVR and BPND was within 10% between 25–35 min and 63–73 min (Fig. 6).
Although the AMPAR-specific binding of [18F]K-40 is not related to sex in the preclinical study and the results of the present study are applicable to women, further studies to clarify the sexual difference of AMPAR distribution are desirable.
In this study, [18F]K-40 and [11C]K-2 imaging were performed on the same subjects at intervals of 2–4 wk. For all subjects, highly comparable images were obtained from the 2 PET scans. This indicates the high equivalence of [18F]K-40 and [11C]K-2, as well as the high reproducibility of AMPAR PET. In the future, test–retest studies will be conducted to further demonstrate the high reproducibility of AMPAR PET.
The small yield of [18F]K-40 synthesis (23) is a limitation of this study. This needs to be addressed in future research.
CONCLUSION
AMPAR PET was launched using an excellent PET drug, [11C]K-2. The arrival of the 18F-labeled AMPAR PET drug, [18F]K-40, further accelerated this trend. [18F]K-40 displayed kinetics similar to those of the well-validated [11C]K-2, and the BPND obtained from each showed a very good correlation. The SUVR, using white matter as the reference region, was well proportional to the BPND. Based on the evidence described in this study, [18F]K-40 is an excellent AMPAR PET drug for AMPAR quantification without blood sampling.
DISCLOSURE
Takuya Takahashi and Tomoyuki Miyazaki are the inventors of a patent application for a novel compound that specifically binds to the AMPA receptor (WO 2,017,006,931), including [11C]K-2. Takuya Takahashi, Tomoyuki Miyazaki, and Tetsu Arisawa are the founders and also stockholders of Ampametry Co. Ltd., which holds the exclusive license to use [11C]K-2. This project was supported by Special Coordination Funds for Promoting Science and Technology under Grant No. 20H05922 and AMED (Grant No. JP24wm0625304 to Takuya Takahashi). This study was also supported by Takeda Science Foundation. No other potential conflict of interest relevant to this article was reported.
KEY POINTS
QUESTION: Does the new 18F-labeled PET tracer, [18F]K-40, quantify AMPAR density in humans?
PERTINENT FINDINGS: [18F]K-40 showed similar kinetics to the existing AMPAR PET tracer, [11C]K-2, with balanced functions of brain uptake, reversible behavior, and AMPAR-specific binding ability. The white matter was applicable as a reference region. The SUVR acquired from a 10-min static scan 40 min after the administration was compatible with BPND.
IMPLICATIONS FOR PATIENT CARE: [18F]K-40 enables off-site production and distribution of the AMPAR PET tracer, accelerating the development of diagnostics for neuropsychiatric disorders.
Footnotes
Published online May 8, 2025.
- © 2025 by the Society of Nuclear Medicine and Molecular Imaging.
Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: https://creativecommons.org/licenses/by/4.0/. Details: https://jnm.snmjournals.org/page/permissions.
REFERENCES
- Received for publication December 20, 2024.
- Accepted for publication April 8, 2025.
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