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Depression in patients with brain tumors is associated with impaired quality of life and shorter survival. Altered metabolism of tryptophan to serotonin and kynurenine metabolites may play a role in tumor-associated depression. Our recent studies with alpha[11C]methyl-L-tryptophan (AMT)-PET in brain tumor patients indicated abnormal tryptophan metabolism not only in the tumor mass but also in normal-appearing contralateral brain. In the present study, we explored if tryptophan metabolism in such brain regions is associated with depression. Twenty-one patients (mean age: 57 years) with a brain tumor (10 meningiomas, 8 gliomas, and 3 brain metastases) underwent AMT-PET scanning. MRI and AMT-PET images were co-registered, and AMT kinetic parameters, including volume of distribution (VD’, an estimate of net tryptophan transport) and K (unidirectional uptake, related to tryptophan metabolism), were measured in the tumor mass and in unaffected cortical and subcortical regions contralateral to the tumor. Depression scores (based on the Beck Depression Inventory-II [BDI-II]) were correlated with tumor size, grade, type, and AMT-PET variables. The mean BDI-II score was 12 ± 10 (range: 2–33); clinical levels of depression were identified in seven patients (33 %). High BDI-II scores were most strongly associated with high thalamic AMT K values both in the whole group (Spearman’s rho = 0.63, p = 0.004) and in the subgroup of 18 primary brain tumors (r = 0.68, p = 0.004). Frontal and striatal VD’ values were higher in the depressed subgroup than in non-depressed patients (p < 0.05); the group difference was even more robust when moderately/severely depressed patients were compared to patients with no/mild depression (frontal: p = 0.005; striatal: p < 0.001). Tumor size, grade, and tumor type were not related to depression scores. Abnormalities of tryptophan transport and metabolism in the thalamus, striatum, and frontal cortex, measured by PET, are associated with depression in patients with brain tumor. These changes may indicate an imbalance between the serotonin and kynurenine pathways and serve as a molecular imaging marker of brain tumor-associated depression. ClinicalTrials.gov NCT02367469

High-performance time-of-flight (TOF) positron emission tomography (PET) systems have the capability for rapid data acquisition while preserving diagnostic image quality. However, determining a reliable and clinically applicable cut-off of the acquisition time plays an important role in routine practice. This study aimed to assess the diagnostic equivalence of short acquisition time of 57 with routine 75 seconds per bed position (s/BP) of [18F]-fluoro-deoxy-glucose (FDG) PET. Phantom studies applying EARL criteria suggested the feasibility of shortened acquisition time in routine clinical imaging by 3D TOF PET/CT scanners. Ninety-six patients with melanoma, lung or head and neck cancer underwent a standard whole-body, skull base-to-thigh or vertex-to-thigh [18F]-FDG PET/CT examination using the 3D TOF Ingenuity TF PET/CT system (Philips, Cleveland, OH). The [18F]-FDG activity applied was equal to 4MBq per kg body weight. Retrospectively, PET list-mode data were used to calculate a second PET study per patient with a reduced acquisition time of 57 s instead of routine 75 s/BP. PET/CT data were reconstructed using a 3D OSEM TOF algorithm. Blinded patient data were analysed by two nuclear medicine physicians. The number of [18F]-FDG-avid lesions per body region (head&neck, thorax, abdomen, bone, extremity) and image quality (grade 1–5) were evaluated. Semiquantitative analyses were performed by standardized uptake value (SUV) measurements using 3D volume of interests (VOI). The visual and semiquantitative diagnostic equivalence of 214 [18F]-FDG-avid lesions were analysed in the routine standard (75 s/BP) as well as the calculated PET/CT studies with short acquisition time. Statistical analyses were performed by equivalence testing and Bland–Altman plots. Lesion detection rate per patient’s body region agreed in > 98% comparing 57 s/BP and 75 s/BP datasets. Overall image quality was determined as equal or superior to 75 s in 80% and 69%, respectively. In the semiquantitative lesion-based analyses, a significant equivalence was found between the 75 s/BP and 57 s/BP PET/CT images both for SUVmax (p = 0.004) and SUVmean (p = 0.003). The results of this study demonstrate significant clinical and semiquantitative equivalence between short acquisition time of 57 s/BP and standard 75 s/BP 3D TOF [18F]-FDG PET/CT scanning, which may improve the patient’s workflow in routine practice.

Overexpression of syndecan-1 (CD138) in breast carcinoma correlates with a poor prognosis and an aggressive phenotype. The objective of this study was to evaluate the potential of targeting CD138 by immuno-PET imaging and radioimmunotherapy (RIT) using the antihuman syndecan-1 B-B4 mAb radiolabeled with either ¹²⁴I or ¹³¹I in nude mice engrafted with the triple-negative MDA-MB-468 breast cancer cell line.

The immunoreactivity of ¹²⁵I-B-B4 (80%) was determined, and the affinity of ¹²⁵I-B-B4 and the expression of CD138 on MDA-MB-468 was measured in vitro by Scatchard analysis. CD138 expression on established tumors was confirmed by immunohistochemistry. A biodistribution study was performed in mice with subcutaneous MDA-MB-468 and ¹²⁵I-B-B4 at 4, 24, 48, 72, and 96 h after injection and compared with an isotype-matched control. Tumor uptake of B-B4 was evaluated in vivo by immuno-PET imaging using the ¹²⁴I-B-B4 mAb. The maximum tolerated dose (MTD) was determined from mice treated with ¹³¹I-B-B4 and the RIT efficacy evaluated.

¹²⁵I-B-B4 affinity was in the nanomolar range (Kd = 4.39 ± 1.10 nM). CD138 expression on MDA-MB-468 cells was quite low (Bmax = 1.19 × 10⁴ ± 9.27 × 10² epitopes/cell) but all expressed CD138 in vivo as determined by immunohistochemistry. The tumor uptake of ¹²⁵I-B-B4 peaked at 14% injected dose (ID) per gram at 24 h and was higher than that of the isotype-matched control mAb (5% ID per gram at 24 h). Immuno-PET performed with ¹²⁴I-B-B4 on tumor-bearing mice confirmed the specificity of B-B4 uptake and its retention within the tumor. The MTD was reached at 22.2 MBq. All mice treated with RIT (n = 8) as a single treatment at the MTD experienced a partial (n = 3) or complete (n = 5) response, with three of them remaining tumor-free 95 days after treatment.

These results demonstrate that RIT with ¹³¹I-B-B4 could be considered for the treatment of metastatic triple-negative breast cancer that cannot benefit from hormone therapy or anti-Her2/neu immunotherapy. Immuno-PET for visualizing CD138-expressing tumors with ¹²⁴I-B-B4 reinforces the interest of this mAb for diagnosis and quantitative imaging.

Positron emission tomography/magnetic resonance imaging (PET/MRI) is a promising diagnostic imaging tool for the diagnosis of dementia, as PET can add complementary information to the routine imaging examination with MRI. The purpose of this study was to evaluate the influence of MRI-based attenuation correction (MRAC) on diagnostic assessment of dementia with [18F]FDG PET. Quantitative differences in both [18F]FDG uptake and z-scores were calculated for three clinically available (DixonNoBone, DixonBone, UTE) and two research MRAC methods (UCL, DeepUTE) compared to CT-based AC (CTAC). Furthermore, diagnoses based on visual evaluations were made by three nuclear medicine physicians and one neuroradiologist (PETCT, PETDeepUTE, PETDixonBone, PETUTE, PETCT + MRI, PETDixonBone + MRI). In addition, pons and cerebellum were compared as reference regions for normalization. The mean absolute difference in z-scores were smallest between MRAC and CTAC with cerebellum as reference region: 0.15 ± 0.11 σ (DeepUTE), 0.15 ± 0.12 σ (UCL), 0.23 ± 0.20 σ (DixonBone), 0.32 ± 0.28 σ (DixonNoBone), and 0.54 ± 0.40 σ (UTE). In the visual evaluation, the diagnoses agreed with PETCT in 74% (PETDeepUTE), 67% (PETDixonBone), and 70% (PETUTE) of the patients, while PETCT + MRI agreed with PETDixonBone + MRI in 89% of the patients. The MRAC research methods performed close to that of CTAC in the quantitative evaluation of [18F]FDG uptake and z-scores. Among the clinically implemented MRAC methods, DixonBone should be preferred for diagnostic assessment of dementia with [18F]FDG PET/MRI. However, as artifacts occur in DixonBone attenuation maps, they must be visually inspected to assure proper quantification.

The experimental outcomes of small-animal positron emission tomography (PET) imaging with 18F-labelled fluorodeoxyglucose (18F-FDG) can be particularly compromised by animal preparation and care. Several works intend to improve research reporting and amplify the quality and reliability of published research. Though these works provide valuable information to plan and conduct animal studies, manuscripts describe different methodologies—standardization does not exist. Consequently, the variation in details reported can explain the difference in the experimental results found in the literature. Additionally, the resources and guidelines defining protocols for small-animal imaging are scarce, making it difficult for researchers to obtain and compare accurate and reproducible data. Considering the selection of suitable procedures key to ensure animal welfare and research improvement, this paper aims to prepare the way for a future guideline on mice preparation and care for PET imaging with 18F-FDG. For this purpose, a global standard protocol was created based on recommendations and good practices described in relevant literature.

Yoga is increasingly popular worldwide with several physical and mental benefits, but the underlying neurobiology remains unclear. Whereas many studies have focused on pure meditational aspects, the triad of yoga includes meditation, postures, and breathing. We conducted a cross-sectional study comparing experienced yoga practitioners to yoga-naive healthy subjects using a multiparametric 2 × 2 design with simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging. 18F-FDG PET, morphometric and diffusion tensor imaging, resting state fMRI, and MR spectroscopy were acquired in 10 experienced (4.8 ± 2.3 years of regular yoga experience) yoga practitioners and 15 matched controls in rest and after a single practice (yoga practice and physical exercise, respectively). In rest, decreased regional glucose metabolism in the medial temporal cortex, striatum, and brainstem was observed in yoga practitioners compared to controls (p < 0.0001), with a significant inverse correlation of resting parahippocampal and brainstem metabolism with years of regular yoga practice (ρ < − 0.63, p < 0.05). A single yoga practice resulted in significant hypermetabolism in the cerebellum (p < 0.0001). None of the MR measures differed, both at rest and after intervention. Experienced yoga practitioners show regional long-term decreases in glucose metabolism related to years of practice. To elucidate a potential causality, a prospective longitudinal study in yoga-naive individuals is warranted.

Programmed cell death 1 (PD-1) inhibitors act as immune checkpoint inhibitors and are more effective for improving survival time with less toxicity as compared with conventional chemotherapies. In anti PD-1 therapy, it is important to evaluate metabolism in the cancer microenvironment, as this helps to clarify the pathological conditions. Herein, we investigate the early effects of PD-1 therapy on 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) uptake in vivo, focusing on cell distribution and glycolysis in both cancer and immune cells. In a B16F10 melanoma model, [18F]FDG-positron emission tomography (PET) was performed before treatment and 7 days after the start of treatment. Values were calculated as the percentage-injected activity per gram of tissue (%IA/g). Flow-cytometry was then performed to assess immune cell populations and glucose metabolism. There was a negligible difference in [18F]FDG uptake between tumors in the treatment group and non-treatment group before the treatment. In contrast, mean [18F]FDG uptake in the treatment group tumors was significantly higher (8.06 ± 0.48 %IA/g; P = 0.0074) than that in the non-treatment group (4.02 ± 1.03 %IA/g) after anti PD-1 treatment. Assessment of tumor immune cell populations showed that treatment slightly enriched CD8+ T cells and CD4+ T cells; however, infiltration of immune cells was negligible, and thus, immune cells were not responsible for the increase in [18F]FDG uptake. On the other hand, anti PD-1 treatment significantly increased glucose transporter 1 (GLUT1) and hexokinase II expression in CD45− cancer cells, indicating that anti PD-1 treatment increased glucose metabolism in cancer cells. The present study shows that anti PD-1 therapy increases glucose metabolism in cancer cells.

We aimed to assess the positivity, distribution, quantitative degree of vessel inflammation, and clinical characteristics of IgG4-related aortitis/periarteritis and periarteritis (IgG4-aortitis), and to examine the difference in these characteristics between cases with and without IgG4-aortitis, using fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) co-registered with contrast-enhanced CT (CECT). We retrospectively evaluated 37 patients with IgG4-related disease (IgG4-RD) who underwent both FDG-PET/CT and CECT. The arterial SUVmax and its value normalized to the background venous blood pool (BP)—the target-to-background ratio (TBR) in the entire aorta and the major first branches—were measured. Active vascular inflammation was considered in cases with a higher FDG uptake than BP and a thickened arterial wall (>2 mm). Fifteen (41%) patients exhibited IgG4-aortitis. Most patients (80%) showed multiple region involvement. The entire aorta, including the major first branches, were involved, typically showing a thickened wall and high FDG uptakes. The most common site was the iliac arteries (35%), followed by the infrarenal abdominal aorta (33%), thoracic aorta (8%), first branches of the thoracic aorta (8%), suprarenal abdominal aorta (6%), and the first branches of the abdominal aorta (5%). The IgG4-aortitis-positive vessel regions were thickened, with an average maximal wall thickness of 6.3 ± 2.9 mm. The SUVmax and TBR values were significantly higher in the IgG4-aortitis-positive regions (median 3.7 [1.6–5.5] and 2.1 [1.4–3.7], respectively) than in the IgG4-aortitis-negative regions (median 2.1 [1.2–3.7] and 1.3 [0.9–2.3], respectively; p < 0.0001). The IgG4-aortitis-positive group patients were older (69.5 ± 6.0 vs. 63.3 ± 12.6 years, respectively) and had a higher male predominance (80 vs. 55%, respectively) than the negative group, although the differences were not significant (p = 0.17 and p = 0.06, respectively). We investigated the image characteristics of IgG4-aortitis. The entire aorta and major branches can be involved with more than 2-fold higher FDG uptake than the venous background pool, and with wall thickening. The most common involved site is the iliac arteries, followed by the infrarenal abdominal aorta.