18F-Fluoride PET/CT for detection of sacroiliitis in ankylosing spondylitis

Purpose: The aim of this study was to evaluate the performance of 18F-fluoride-PET/CT (PET/CT) for the diagnosis of sacroiliac joint (SIJ) arthritis in patients with active ankylosing spondylitis (AS). Methods: Included in the study were 15 patients with AS according to the modified New York criteria (AS group) and with active disease and 13 patients with mechanical low back pain (MLBP; control group) who were investigated with whole-body 18F-fluoride PET/CT. The ratio of the uptake in the SIJ and that in the sacrum (SIJ/S) was calculated for every joint. Results: The mean SIJ/S ratio of 30 quantified joints in the AS group was 1.66 (range 1.10-3.07) with PET/CT, and the mean SIJ/S ratio of 26 quantified joints in the MLBP group was 1.12 (range 0.71-1.52). The area under the receiver operating characteristic curve for SIJ arthritis was 0.84. With plain radiography as a the gold standard and taking an SIJ/S ratio of >1.3 as the threshold, the sensitivity, specificity and accuracy on a per patient basis were 80%, 77% and 79%, respectively. On a per SIJ basis, the greatest sensitivity (94%) was found in grade 3 sacroiliitis (n = 16). Conclusion: Our results suggest that quantitative 18F-fluoride PET/CT may play a role in the diagnosis of sacroiliitis in active AS and is an alternative to conventional bone scintigraphy in times of molybdenum shortag

Assessment of successful incorporation of cages after cervical or lumbar intercorporal fusion with [(18)F]fluoride positron-emission tomography/computed tomography

The purpose of this study is to assess the successful incorporation of cages in patients after cervical or lumbar intercorporal fusion with positron-emission tomography/computed tomography (PET/CT). Twenty patients (14 female and 6 male; mean age 58years, age range 38-73years) with 30 cervical (n=13) or lumbar (n=17) intercorporal fusions were prospectively enrolled in this study. Time interval between last intercorporal intervention and PET/CT ranged from 2 to 116months (mean 63; median 77months). IRB approval was obtained for all patients, and written informed consent was obtained from all patients. About 30min prior to PET/CT scanning, 97-217MBq (mean 161MBq) 18F-fluoride were administered intravenously. Patients were imaged in supine position on a combined PET/CT system (Discovery RX/STE, 16/64 slice CT, GE Healthcare). 3D-PET emission data were acquired for 1.5 and 2min/bed position, respectively, and reconstructed by a fully 3D iterative algorithm (VUE Point HD) using low-dose CT data for attenuation correction. A dedicated diagnostic thin-slice CT was optionally acquired covering the fused region. Areas of increased 18F-fluoride uptake around cages were determined by one double-board certified radiologist/nuclear physician and one board certified radiologist in consensus. In 12/20 (60%) patients, increased 18F-fluoride uptake around cages was observed. Of the 30 intercorporal fusions, 15 (50%) showed increased 18F-fluoride uptake. Median time between intervention and PET/CT examination in cages with increased uptake was 37months (2-116months), median time between intervention and PET/CT examination in those cages without increased uptake was 91months (19-112months), p (Wilcoxon)=0.01 (one-sided). 14/29 (48%) cages with a time interval>1year between intervention and PET/CT scan showed an increased uptake. In conclusion, PET/CT frequently shows increased 18F-fluoride uptake in cervical and lumbar cages older than 1year (up to almost 8years in cervical cages and 10years in lumbar cages) possibly indicating unsuccessful fusion due to increased stress/microinstabilit

Multimodal PET-MRS Investigation of Glutamate-Dependent Neuroreceptor Plasticity in the Healthy Human Brain

In this multimodal, double-blind, randomized, placebo-controlled PET-MRS study in 20 healthy subjects, we report a pharmacological modulation of glutamate-dependent neuroreceptor plasticity in the pregenual anterior cingulate cortex following the administration of the NMDA-receptor antagonist ketamine. In order to investigate the functional interplay between the major excitatory neurotransmitter glutamate (Glu) and the density of the metabotropic glutamate receptor subtype 5 (mGluR5) we combined proton magnetic resonance spectroscopy (1H-MRS) with positron emission tomography (11C-ABP688-PET). Our findings complement previous reports of increased glutamate release during ketamine challenge by providing additional in vivo molecular imaging evidence for ketamine-induced neurotransmitter-receptor coupling

The Role of Metabotropic Glutamate Receptors in Ketamine-induced Altered States of Consciousness: A Multimodal PET-MRS Approach

Background: Recent findings highlight the role of glutamate-driven synaptic plasticity in the therapeutic action of psychedelic drugs such as ketamine. Since metabotropic glutamate receptors 5 (mGluR5) interact closely with NMDA receptors and play an important role in the modulation of glutamatergic signalling, we assessed glutamate-dependent mGluR5 plasticity following ketamine-induced NMDA-R antagonism using a multimodal PET-MRS imaging approach. Methods: We quantified mGluR5 densities using 11C-ABP688-PET and glutamate levels in the pregenual anterior cingulate cortex (PACC) using 1H-MRS in 20 healthy subjects. Before scanning, either placebo or S-ketamine (i.v. bolus of 0.12 mg/kg, infusion of 0.25 mg/kg/h over 40 min) was administered in a doubleblind randomized manner. Results: Post-infusion glutamate levels and mGluR5 densities were highly correlated in the PACC following ketamine challenge but did not show any significant relation under placebo conditions. Anterior cingulate mGluR5 densities predicted psychedelic alterations of consciousness during ketamine infusion. Conclusions: To our knowledge, this is the first double-blind, randomized, placebo-controlled PET-MRS study that reports a pharmacological modulation of glutamate-dependent mGluR5 plasticity in vivo. Our findings complement previous reports of increased glutamate release during ketamine challenge by providing additional evidence for glutamate-mGluR5 coupling. Specifically, we raise the hypothesis that mGluR5 might play a critical role in mediating ketamineinduced alterations of consciousness as part of its therapeutic action

Observation of synaptic plasticity in the healthy human brain upon Ketamine infusion by 11C-ABP688-PET and 2D J-resolved 1H MRS

Introduction Information processing in the brain relies on the release and diffusion of neurotransmitter molecules across the synaptic cleft and on functional coupling to postsynaptic receptors, which in turn depends on the receptor plasticity. Here, we investigate the functional interplay between the major excitatory neurotransmitter glutamate (Glu) as measured by 1H-MRS and the density of the metabotropic glutamate receptor subtype 5 (mGluR5) assessed by PET. As a tool compound, we used the NMDA-receptor antagonist ketamine that was robustly shown to increase synaptic glutamate release (1). Methods 20 sex- and age-matched healthy subjects completed two imaging sessions (7 days apart) including 11C-ABP688-PET (2) performed on a PET/CT scanner (GE Medical Systems) followed by a 2D J-resolved PRESS 1H-MRS sequence scan (3) on a 3T whole-body MRI scanner (Philips Healthcare). Single voxel spectra were quantified using ProFit V2.0 (3). Metabolite levels were normalized to internal water and a segmentation based volume tissue composition correction was applied (4). PET data were analyzed using PMOD according to well established routines (5); averaged mGluR5 densities from the spectroscopy VOI were extracted. Before PET scanning, either placebo or S-ketamine (i.v. bolus of 0.12 mg/kg, infusion of 0.25 mg/kg/h over 40 min) was administered in a cross-over, double-blind, and randomized study design. Results We found highly significant correlations between post-infusion glutamate levels and mGluR5 densities (r = -.614, p = .005) as well as between post-infusion glutamate and choline levels (r=0.620, p=0.005) in the PACC following ketamine challenge, whereas none of these correlations were apparent under placebo conditions (Fig 2). Additional pairwise comparisons revealed increased total choline (tCho) metabolite levels (p = .044) after ketamine administration (0.440 ± 0.051) compared to placebo (0.418 ± 0.042). Conclusions Pharmacological modulation of the glutamatergic neurotransmitter – receptor system is assessed in the human brain for the first time. The increase in total choline levels along with the glutamate – choline correlation following ketamine infusion are likely to reflect an increase in synaptic glutamate release and related remodeling of cell membranes

Relation of dopamine receptor 2 binding to pain perception in female fibromyalgia patients with and without depression - A [(11)C] raclopride PET-study

Dopamine D2/D3 receptor availability at rest and its association with individual pain perception was investigated using the [(11)C] raclopride PET-method in 24 female Fibromyalgia (FMS) participants with (FMS+, N=11) and without (FMS-, N=13) comorbid depression and in 17 healthy women. Thermal pain thresholds (TPT) and pain responses were assessed outside the scanner. We compared the discriminative capacity, i.e. the individual׳s capacity to discriminate between lower and higher pain intensities and the response criterion, i.e. the subject׳s tendency to report pain during noxious stimulation due to psychological factors. [(11)C] raclopride binding potential (BP), defined as the ratio of specifically bound non-displaceable radioligand at equilibrium (BPND) was used as measure of D2/D3 receptor availability. We found significant group effects of BPND in striatal regions (left ventral striatum, left caudate nucleus and left nucleus accumbens) between FMS+ and FMS- compared to healthy subjects. Correlational analysis showed negative associations between TPT and D2/D3 receptor availability in the left caudate nucleus in FMS-, between TPT and D2/D3 receptor availability in the right caudate nucleus in FMS + and positive associations between TPT and D2/D3 receptor availability in the left putamen and right caudate nucleus in healthy controls. The response criterion was positively associated with D2/D3 receptor availability in the right nucleus accumbens in FMS - and negatively with D2/D3 receptor availability in the left caudate nucleus in healthy controls. Finally, no significant associations between D2/D3 receptor availability and discriminative capacity in any of the groups or regions were determined. These findings provide further support for a disruption of dopaminergic neurotransmission in FMS and implicate DA as important neurochemical moderator of differences in pain perception in FMS patients with and without co-morbid depression

Therapeutic impact of [(18)F]fluoride positron-emission tomography/computed tomography on patients with unclear foot pain

[(18)F]fluoride PET/CT has a substantial therapeutic impact on management in patients with unclear foot pain

18F-Fluoride PET/MR for painful lumbar facet joint degeneration - a randomized controlled clinical trial

BACKGROUND CONTEXT [18F]-sodium fluoride (NaF) PET/MR is a modern diagnostic modality for imaging increased bone turnover. Its merits in detecting painful facet joint osteoarthritis in patients with lumbar back pain are unknown. PURPOSE To perform a prospective randomized controlled study investigating [18F]-NaF PET/MR for detecting painful facet joints in comparison to the standard of care (SOC), including clinical examination and conventional MRI. STUDY DESIGN/SETTING Randomized controlled clinical study. PATIENT SAMPLE Thirty-nine patients. OUTCOME MEASURES Visual analog pain scale (VAS) before and at several time points after facet joint infiltration. METHODS Patients with low back pain and suspected facet joint osteoarthritis underwent lumbar [18F]-NaF PET/MR, besides conventional MRI and clinical examination. After randomization, they either received local anesthetics/ corticosteroid infiltration of facet joints as defined by clinical examination and conventional MRI (SOC), or according to the hot spots on PET/MR. VAS was documented at 15 minutes, 1 day, 1 week and 1 month after infiltration. Thirty-nine patients underwent PET/MR before the study was stopped due to new Good Manufacturing Practice requirement and new regulations by radiation protection authorities limiting staff radiation exposure during the production of this radiotracer. RESULTS Significant pain reduction compared to baseline was shown at every timepoint in both groups, except at 1 month after infiltration in the SOC group. Pain levels did not differ between SOC (n=17) and PET/MR patients (n=12) before infiltration and at 15 minutes, 1 day, 1 week and 1 month after infiltration. No significant correlation was detected between the sum of the PET/MR activity and the initial pain scores or relative reduction of pain after 15 minutes. The constructed study groups of patients with infiltration of all facet joints being PET/MR-positive (n=18) had significantly less pain after 1 months than patients with infiltration in PET/MR-negative facet joints (n=11) (VAS: 4 [0, 9] vs. 7 [2, 10], p=.046). CONCLUSIONS There is no correlation of pain to NaF activity nor a relevant superiority of [18F]-NaF PET/MR for identification of painful facet joints compared to the standard of care