Publications by authors named "Marcus Hacker"

285 Publications

Impaired coronary flow reserve in patients with supra-normal left ventricular ejection fraction at rest.

Eur J Nucl Med Mol Imaging 2022 Jan 6. Epub 2022 Jan 6.

Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Purpose: Recently, a "U" hazard ratio curve between resting left ventricular ejection fraction (LVEF) and prognosis has been observed in patients referred for routine clinical echocardiograms. The present study sought to explore whether a similar "U" curve existed between resting LVEF and coronary flow reserve (CFR) in patients without severe cardiovascular disease (CVD) and whether impaired CFR played a role in the adverse outcome of patients with supra-normal LVEF (snLVEF, LVEF ≥ 65%).

Methods: Two hundred ten consecutive patients (mean age 52.3 ± 9.3 years, 104 women) without severe CVD underwent clinically indicated rest/dipyridamole stress electrocardiography (ECG)-gated  N-ammonia positron emission tomography/computed tomography (PET/CT). Major adverse cardiac events (MACE) were followed up for 27.3 ± 9.5 months, including heart failure, late revascularization, re-hospitalization, and re-coronary angiography for any cardiac reason. Clinical characteristics, corrected CFR (cCFR), and MACE were compared among the three groups categorized by resting LVEF detected by PET/CT. Dose-response analyses using restricted cubic spline (RCS) functions, multivariate logistic regression, and Kaplan-Meier survival analysis were conducted to evaluate the relationship between resting LVEF and CFR/outcome.

Results: An inverted "U" curve existed between resting LVEF and cCFR (p = 0.06). Both patients with snLVEF (n = 38) and with reduced LVEF (rLVEF, LVEF < 55%) (n = 66) displayed a higher incidence of reduced cCFR than those with normal LVEF (nLVEF, 55% ≤ LVEF < 65%) (n = 106) (57.9% vs 54.5% vs 34.3%, p < 0.01, respectively). Both snLVEF (p < 0.01) and rLVEF (p < 0.05) remained independent predictors for reduced cCFR after multivariable adjustment. Patients with snLVEF encountered more MACE than those with nLVEF (10.5% vs 0.9%, log-rank p = 0.01).

Conclusions: Patients with snLVEF are prone to impaired cCFR, which may be related to the adverse prognosis. Further investigations are warranted to explore its underlying pathological mechanism and clinical significance.
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http://dx.doi.org/10.1007/s00259-021-05566-yDOI Listing
January 2022

Active Brown Adipose Tissue is Associated With a Healthier Metabolic Phenotype in Obesity.

Diabetes 2021 Oct 18. Epub 2021 Oct 18.

Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

Obesity is associated with increasing cardiometabolic morbidity and mortality worldwide. Not everyone with obesity, however, develops metabolic complications. Brown adipose tissue (BAT) has been suggested as a promoter of leanness and metabolic health. To date, little is known about the prevalence and metabolic function of BAT in subjects with severe obesity, a population at high cardiometabolic risk. In this cross-sectional study, we included 40 individuals with WHO class II-III obesity (BMI ≥ 35 kg/m2). Employing a 150-minute personalized cooling protocol and 18F-fluorodeoxyglucose positron emission tomography/computed tomography, cold-activated BAT was detectable in 14 (35%) of the participants. Cold-induced thermogenesis was significantly higher in participants with detectable BAT compared to those without. Notably, individuals with obesity and active BAT had 28.8% lower visceral fat mass despite slightly higher total fat mass compared to those without detectable BAT 18F-FDG uptake. This was accompanied by lower insulin resistance and systemic inflammation and improved NAFLD parameters, all adjusted for age, sex, and percent body fat. Contrary to previous assumptions, we show here that a significant fraction of individuals with severe obesity has active BAT. We found that decreased BAT 18F-FDG uptake was not associated with adiposity per se but with higher visceral fat mass. In summary, active BAT is linked to a healthier metabolic phenotype in obesity.
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http://dx.doi.org/10.2337/db21-0475DOI Listing
October 2021

Unexpected scaffold rearrangement product of pirenzepine found in commercial samples.

Sci Rep 2021 12 3;11(1):23397. Epub 2021 Dec 3.

Department of Pharmaceutical Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria.

Pharmacovigilance aims at a better understanding of the molecular events triggered by medications to prevent adverse effects, which despite significant advances in our analytical repertoire plague the use of drugs until today. In this study, we find that clinically prescribed and commercially available pirenzepine may not be the correct compound. Pirenzepine can undergo an unexpected scaffold rearrangement from the pharmaceutical active ingredient (API) to a previously uncharacterized benzimidazole. The rearrangement occurs under highly acidic conditions, which were believed to favour the dihydrochloride formation of pirenzepine. The rearranged products of pirenzepine and the structurally related telenzepine have significantly decreased affinity for the muscarinic acetylcholine receptor, the pharmacological target of these compounds. Fortunately, in situ rearrangement after oral application is no safety issue, as we show that reaction kinetics in gastric acid prevent rearrangement. The research community should consider appropriate measures to perform reliable receiving inspections in the commercial supply of well described and frequently used chemicals, in particular if experiments yield unexpected results.
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http://dx.doi.org/10.1038/s41598-021-02732-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642400PMC
December 2021

Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age.

Biology (Basel) 2021 Nov 19;10(11). Epub 2021 Nov 19.

Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria.

Immune checkpoint inhibitors (ICI) have transformed the management of various cancers. Serious and potentially fatal cardiovascular toxicity, as well as a progression of atherosclerosis, have been described, mainly in elderly and comorbid patients. We investigated 117 arterial segments of 12 young (under 50 years of age), otherwise healthy lymphoma patients pre/post-ICI treatment using 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Maximum FDG standardized uptake values (SUV) and target-to-background ratios (TBRs) were calculated along arterial segments. Additionally, metabolic activities (SUV) of the bone marrow, spleen, and liver were analyzed. The levels of high-sensitivity C-reactive protein (hsCRP) were assessed. ICI therapy induced arterial inflammatory activity, detected by increased TBR in arterial segments without pre-existing inflammation (TBRneg_pre = 1.20 ± 0.22 vs. TBRneg_post = 1.71 ± 0.45, < 0.001), whereas already-inflamed lesions remained unchanged. Dormant calcified segments (Hounsfield Units-HU ≥ 130) showed a significant increase in TBR values after ICI treatment (TBRcalc_pre = 1.36 ± 0.38 vs. TBRcalc_post = 1.76 ± 0.42, < 0.001). FDG uptake measured in other organs and hsCRP levels remained unchanged after ICI therapy. Although the effects of ICI therapy on arterial inflammation are still incompletely understood, cancer immunotherapy might be a critical moderator of atherosclerosis with a subsequently increased risk of future cerebro- and/or cardiovascular events in young oncological patients.
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http://dx.doi.org/10.3390/biology10111206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615286PMC
November 2021

Active Brown Adipose Tissue is Associated With a Healthier Metabolic Phenotype in Obesity.

Diabetes 2021 Oct 18. Epub 2021 Oct 18.

Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria

Obesity is associated with increasing cardiometabolic morbidity and mortality worldwide. Not everyone with obesity, however, develops metabolic complications. Brown adipose tissue (BAT) has been suggested as a promoter of leanness and metabolic health. To date, little is known about the prevalence and metabolic function of BAT in subjects with severe obesity, a population at high cardiometabolic risk. In this cross-sectional study, we included 40 individuals with WHO class II-III obesity (BMI ≥ 35 kg/m). Employing a 150-minute personalized cooling protocol and F-fluorodeoxyglucose positron emission tomography/computed tomography, cold-activated BAT was detectable in 14 (35%) of the participants. Cold-induced thermogenesis was significantly higher in participants with detectable BAT compared to those without. Notably, individuals with obesity and active BAT had 28.8% lower visceral fat mass despite slightly higher total fat mass compared to those without detectable BAT F-FDG uptake. This was accompanied by lower insulin resistance and systemic inflammation and improved NAFLD parameters, all adjusted for age, sex, and percent body fat. Contrary to previous assumptions, we show here that a significant fraction of individuals with severe obesity has active BAT. We found that decreased BAT F-FDG uptake was not associated with adiposity per se but with higher visceral fat mass. In summary, active BAT is linked to a healthier metabolic phenotype in obesity.
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http://dx.doi.org/10.2337/db21-0475DOI Listing
October 2021

Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders.

Cancer Discov 2021 Oct 11. Epub 2021 Oct 11.

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.
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http://dx.doi.org/10.1158/2159-8290.CD-21-0538DOI Listing
October 2021

First-in-human brain PET imaging of the GluN2B-containing N-methyl-D-aspartate receptor with ()-C-Me-NB1.

J Nucl Med 2021 Oct 7. Epub 2021 Oct 7.

Animal Imaging Center-PET, Switzerland.

The N-methyl-D-aspartate receptor (NMDAR) plays a crucial role in neurodegenerative diseases such as Alzheimer's disease and in the treatment of major depression by new fast-acting antidepressants such as ketamine. Given their broad implications, GluN2B-containing NMDARs have been of large interest as diagnostic and therapeutic targets. Recently, ()-C-Me-NB1 was investigated preclinically and shown to be a promising radioligand for imaging GluN2B subunits. Here, we report on the performance characteristics of this novel radioligand in a first-in-human PET study. Six healthy male subjects were scanned twice on a fully-integrated PET/MR scanner with ()-C-Me-NB1 for 120 min. Brain uptake and tracer distribution over time were investigated by standardized uptake values (SUV). Test-retest reliability was assessed with the absolute percentage difference (APD) and the coefficient of variation (COV). Exploratory total volumes of distribution (VT) were computed using an arterial input function and the Logan plot as well as a constrained two-tissue compartment model with K1/k2 coupled (2TCM). SUV was correlated with VT to investigate its potential as a surrogate marker of GluN2B expression. High and heterogeneous radioligand uptake was observed across the entire gray matter with reversible kinetics within the scan time. SUV APD ranged from 6.8 - 8.5% and COV from 4.9 - 6.0%, indicating a high test-retest reliability. A moderate correlation was found between SUV averaged from 70-90 min and VT using Logan plot (Spearman's rho = 0.44). Correlation between VT Logan and 2TCM was r= 0.76. The novel radioligand, ()-C-Me-NB1, was highly effective in mapping GluN2B-enriched NMDARs in the human brain. With a heterogeneous uptake and a high test-retest reliability, this radioligand offers promise to deepen our understanding of the GluN2B-containing NMDA receptor in the pathophysiology and treatment of neuropsychiatric disease such as Alzheimer's disease and major depression. Additionally, it could help in the selection of appropriate doses of GluN2B-targeting drugs.
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http://dx.doi.org/10.2967/jnumed.121.262427DOI Listing
October 2021

Renal and Salivary Gland Functions after Three Cycles of PSMA-617 Therapy Every Four Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer.

Curr Oncol 2021 09 23;28(5):3692-3704. Epub 2021 Sep 23.

Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, 1090 Vienna, Austria.

Background: [Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) could affect kidney and salivary gland functions in metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods: We retrospectively analyzed clinical, renal, and salivary scintigraphy data and salivary [Ga]Ga-PSMA-11 ligand PET scan measures such as metabolic volume and SUVmax values of 27 mCRPC men (mean age 71 ± 7 years) before and 4 weeks after receiving three cycles of PSMA-RLT every 4 weeks. Twenty-two patients additionally obtained renal and salivary scintigraphy prior to each cycle. A one-way ANOVA, post-hoc Scheffé test and Cochran's Q test were applied to assess organ toxicity.

Results: In total, 54 PSMA PET scans, 98 kidney, and 98 salivary scintigraphy results were evaluated. There were no significant differences for the ejection fraction, peak time, and residual activity after 5 min for both parotid and submandibular glands prior to each cycle and 4 weeks after the last cycle. Similarly, no significant differences in serum creatinine and renal scintigraphy parameters were observed prior to each cycle and 4 weeks after the last treatment. Despite there being no changes in the metabolic volume of both submandibular glands, SUVmax values dropped significantly ( < 0.05).

Conclusion: Results evidenced no alterations in renal function and only minimal impairment of salivary function of mCRPC patients who acquired an intense PSMA-RLT regimen every 4 weeks.
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http://dx.doi.org/10.3390/curroncol28050315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482282PMC
September 2021

If It Works, Don't Touch It? A Cell-Based Approach to Studying 2-[F]FDG Metabolism.

Pharmaceuticals (Basel) 2021 Sep 9;14(9). Epub 2021 Sep 9.

Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria.

The glucose derivative 2-[F]fluoro-2-deoxy-D-glucose (2-[F]FDG) is still the most used radiotracer for positron emission tomography, as it visualizes glucose utilization and energy demand. In general, 2-[F]FDG is said to be trapped intracellularly as 2-[F]FDG-6-phosphate, which cannot be further metabolized. However, increasingly, this dogma is being questioned because of publications showing metabolism beyond 2-[F]FDG-6-phosphate and even postulating 2-[F]FDG imaging to depend on the enzyme hexose-6-phosphate dehydrogenase in the endoplasmic reticulum. Therefore, we aimed to study 2-[F]FDG metabolism in the human cancer cell lines HT1080, HT29 and Huh7 applying HPLC. We then compared 2-[F]FDG metabolism with intracellular tracer accumulation, efflux and the cells' metabolic state and used a graphical Gaussian model to visualize metabolic patterns. The extent of 2-[F]FDG metabolism varied considerably, dependent on the cell line, and was significantly enhanced by glucose withdrawal. However, the metabolic pattern was quite conserved. The most important radiometabolites beyond 2-[F]FDG-6-phosphate were 2-[F]FDMannose-6-phosphate, 2-[F]FDG-1,6-bisphosphate and 2-[F]FD-phosphogluconolactone. Enhanced radiometabolite formation under glucose reduction was accompanied by reduced efflux and mirrored the cells' metabolic switch as assessed via extracellular lactate levels. We conclude that there can be considerable metabolism beyond 2-[F]FDG-6-phosphate in cancer cell lines and a comprehensive understanding of 2-[F]FDG metabolism might help to improve cancer research and tumor diagnosis.
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http://dx.doi.org/10.3390/ph14090910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467898PMC
September 2021

Feasibility of in vivo Imaging of Fibroblast Activation Protein in Human Arterial Walls.

J Nucl Med 2021 Sep 16. Epub 2021 Sep 16.

Medical University of Vienna, Austria.

Increased expression of fibroblast activating protein (FAP) in fibrous caps may contribute to progression of atherosclerotic plaques. Forty-one patients who underwent gallium-68-conjugated quinoline-based FAP inhibitor (Ga-FAPI-04) PET/CT for non-cardiovascular indications were retrospectively analyzed. Correlations were assessed between the uptake of Ga-FAPI-04 in large arterial walls (SUV and target-to-background ratio, TBR) and degree of calcification and cardiovascular risk factors. Focal arterial uptake of Ga-FAPI-04 or calcification was detected in 1,177 arterial segments in all 41 patients. TBR was negatively correlated with the degree of calcification (HU) (r = -0.27, < 0.01). Mean TBR in higher-risk patients was greater than lower-risk patients (2.2 ± 0.3 vs. 1.8 ± 0.3, < 0.01). Immunohistochemical labeling of carotid plaques exhibited prominent FAP expression in a thin fibrous cap and moderate FAP expression in a thick cap. Ga-FAPI-04 PET/CT might have potential for imaging fibroblastic activation in the arterial wall.
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http://dx.doi.org/10.2967/jnumed.121.262863DOI Listing
September 2021

CXCR4 PET/MRI for follow-up of gastric mucosa-associated lymphoid tissue lymphoma after first-line Helicobacter pylori eradication.

Blood 2022 Jan;139(2):240-244

Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, and.

Posttreatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G protein-coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate positron emission tomography (PET) with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow up biopsies for assessment of residual disease (noncomplete remission [CR]) after first-line Helicobacter pylori eradication. Forty-six post-H pylori eradication [68Ga]Pentixafor-PET/magnetic resonance imaging (MRI) examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor-PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard and showed CR in 6 cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive values of [68Ga]Pentixafor-PET for detection of residual gastric MALT lymphoma at follow-up were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r = 0.51 and r = 0.52 (P = .008 and P = .006). In summary, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after H pylori eradication.
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http://dx.doi.org/10.1182/blood.2021013239DOI Listing
January 2022

[68Ga]DOTA-TATE PET for the detection of early transplant rejection in a heterotopic allograft heart transplantation model of the rat. A pilot study.

Q J Nucl Med Mol Imaging 2021 Sep 3. Epub 2021 Sep 3.

Department of Nuclear Medicine, University of Munich, Munich, Germany.

Background: The most important cause of heart transplant loss is early acute allograft rejection, caused by the infiltration of lymphocytes, development of edema and myocardial necrosis. It has been propagated that [68Ga]DOTA-TATE PET might be suitable to quantify the presence of SSTR over-expressing lymphocytes. With heterotopic allogenic heart transplant models in the rat readily available, we aimed to investigate, if monitoring and quantification of acute allograft rejection after heterotopic allogenic heart transplantation was feasible by non-invasive serial [68Ga]DOTA-TATE PET.

Methods: 17 Lewis rats (9 for serial PET imaging, 8 for histological correlation) received allogenic heterotopic heart transplants from 17 Brown-Norway rats. On days 4, 6 and 7 a [68Ga]DOTA-TATE PET scan was performed.

Results: Imaging of acute transplant rejection until 7 days after allogenic heart transplantation in the rat is feasible. Heterotopic allografts showed significantly increased tracer uptake on day 4 until day 7 after transplantation, reflecting the process of histologically detected myocardial lymphocytic infiltration. Both the area of infarction and the amount of necrosis increased over the course of 7 days, with necrosis reaching statistical significance.

Conclusions: We purport that the detected PET signal is primarily a specific marker of lymphocyte infiltration and only to a lesser extent an unspecific marker of infarction and necrosis. Thus, [68Ga]DOTA-TATE PET might be a suitable tool for serial imaging and quantification of lymphocyte infiltration as a direct mediator of acute allograft rejection at an early stage after heart transplantation.
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http://dx.doi.org/10.23736/S1824-4785.21.03387-2DOI Listing
September 2021

Combining body mass index with waist circumference to assess coronary microvascular function in patients with non-obstructive coronary artery disease.

J Nucl Cardiol 2021 Sep 3. Epub 2021 Sep 3.

Department of Nuclear Medicine, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan, 030001, Shanxi, China.

Background: Coronary microvascular dysfunction (CMD) may precede clinically overt coronary artery disease (CAD). Overall and central obesity (CO) are major risk factors for CAD. This study sought to investigate the subclinical significance of body adiposity patterns based on the CMD risk.

Methods: A total of 128 patients with non-obstructive CAD were prospectively enrolled. Patients were categorized into 4 anthropometric groups: normal weight and non-CO (NWNCO, n = 41), normal weight and CO (NWCO, n = 20), excess weight and non-CO (EWNCO, n = 26), and excess weight and CO (EWCO, n = 41). Patients underwent rest/stress electrocardiography-gated N-ammonia positron emission tomography to measure absolute myocardial blood flow (MBF), myocardial flow reserve (MFR), hemodynamic parameters, and cardiac function.

Results: Resting MBF did not differ between groups (P = .36). Compared with the NWNCO group, hyperemic MBF and MFR were significantly lower in the NWCO and EWCO groups. Notably, patients with NWCO presented the lowest hyperemic MBF and MFR and the highest incidence of CMD. Waist circumference was an independent risk factor for CMD (OR 1.05, 95% CI 1.01 to 1.10, P = .02).

Conclusion: In patients with non-obstructive CAD, CO may be associated with an increased risk of CMD to better fit the study findings which did not assess management or monitoring of MBF and MFR.
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http://dx.doi.org/10.1007/s12350-021-02788-3DOI Listing
September 2021

High-dose testosterone treatment reduces monoamine oxidase A levels in the human brain: A preliminary report.

Psychoneuroendocrinology 2021 11 6;133:105381. Epub 2021 Aug 6.

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria. Electronic address:

The sex hormones testosterone and estradiol influence brain structure and function and are implicated in the pathogenesis, prevalence and disease course of major depression. Recent research employing gender-affirming hormone treatment (GHT) of gender dysphoric individuals and utilizing positron emission tomography (PET) indicates increased serotonin transporter binding upon high-dosages of testosterone treatment. Here, we investigated the effects of GHT on levels of monoamine oxidase A (MAO-A), another key target of antidepressant treatment. Participants underwent PET with the radioligand [C]harmine to assess cerebral MAO-A distribution volumes (V) before and four months after initiation of GHT. By the time this study was terminated for technical reasons, 18 transgender individuals undergoing GHT (11 transmen, TM and 7 transwomen, TW) and 17 cis-gender subjects had been assessed. Preliminary analysis of available data revealed statistically significant MAO-A V reductions in TM under testosterone treatment in six of twelve a priori defined regions of interest (middle frontal cortex (-10%), anterior cingulate cortex (-9%), medial cingulate cortex (-10.5%), insula (-8%), amygdala (-9%) and hippocampus (-8.5%, all p<0.05)). MAO-A V did not change in TW receiving estrogen treatment. Despite the limited sample size, pronounced MAO-A V reduction could be observed, pointing towards a potential effect of testosterone. Considering MAO-A's central role in regulation of serotonergic neurotransmission, changes to MAO-A V should be further investigated as a possible mechanism by which testosterone mediates risk for, symptomatology of, and treatment response in affective disorders.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105381DOI Listing
November 2021

Single-lesion Prostate-specific Membrane Antigen Protein Expression (PSMA) and Response to [Lu]-PSMA-ligand Therapy in Patients with Castration-resistant Prostate Cancer.

Eur Urol Open Sci 2021 Aug 30;30:63-66. Epub 2021 Jun 30.

Department of Urology, Medical University of Vienna, Vienna, Austria.

Initial reports of a clinical response in patients treated with the radioligand [Lu]-PSMA-617 for castration-resistant prostate cancer (CRPC) are promising, despite known inter- and intrapatient heterogeneity. In metastatic CRPC, we examined the association of baseline immunohistochemical (IHC) expression of prostate-specific membrane antigen (PSMA) in a single lesion and responsiveness to [Lu]-PSMA-617 therapy, measured as the PSMA maximum standardized uptake value (SUV). Between 2015 and 2020, 19 patients with multiple metastases underwent single-lesion biopsy, [Ga]-PSMA positron emission tomography (PET) imaging, and treatment with [Lu]-PSMA-617. A monoclonal anti-PSMA antibody was used to semiquantitatively assess PSMA IHC in the biopsy specimen. Imaging evaluation of the biopsied single lesion and overall response was performed according to Positron Emission Tomography Response Criteria in Solid Tumors. The PSMA IHC histoscore correlated positively with pretreatment same-site PSMA SUV (  = 0.6). Nine patients had imaging after three cycles of [Lu]-PSMA-617 and were included in the lesion-specific analysis. Of these, five patients (55.6%) had an SUV response at the biopsy site, but three experienced overall progression. The histoscore was unable to predict the lesion-specific change in SUV (95% confidence interval [CI] -44.2 to 69.2) or PSA (95% CI-125.2 to 17.2). There was no correlation between single-lesion SUV and overall progression (  = 0.1) on [Ga]-PSMA PET imaging. Additional studies need to interrogate the clinical consequence of PSMA expression heterogeneity in metastases and the association with response to [Lu]-PSMA-671.

Patient Summary: Treatment with a radioactive binding molecule called [Lu]-PSMA-617 for men with prostate cancer resistant to castration (CRPC) is showing promise. We investigated the association between the presence of PSMA protein in metastatic lesions at biopsy and response to [Lu]-PSMA-617 among men with metastatic CRPC. We found that assessment of PSMA presence at biopsy is not a reliable predictor of response to [Lu]-PSMA-617. Additional studies are needed to better determine which CRPC metastatic sites will respond to this therapy.
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http://dx.doi.org/10.1016/j.euros.2021.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317820PMC
August 2021

Characterization of endogenous bile acid composition in individuals with cold-activated brown adipose tissue.

Mol Cell Endocrinol 2021 10 28;536:111403. Epub 2021 Jul 28.

Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address:

Introduction: Bile acid signaling has been suggested to promote BAT activity in various experimental models. However, little is known if and how physiologic bile acid metabolism is linked to BAT function in humans. Here we investigated the association between BAT activity and circulating bile acid concentrations in lean and obese individuals.

Methods: BAT F-fluorodeoxyglucose uptake was measured after a standardized cooling protocol by positron emission tomography/computed tomography. Cold-induced thermogenesis was assessed by indirect calorimetry. Fasting bile acid concentrations were determined by high performance liquid chromatography-high-resolution mass spectrometry.

Results: In a cohort of 24 BAT-negative and 20 BAT-positive individuals matched by age, sex, and body mass index, circulating bile acid levels were similar between groups except for higher ursodeoxycholic acid and a trend towards a lower 12α-OH/non-12α-OH bile acid ratio in lean participants with active BAT compared to those without. Moreover, the 12α-OH/non-12α-OH ratio, a marker of CYP8B1 activity, correlated negatively with BAT volume and activity.

Conclusion: Fasting concentrations of major bile acids are not associated with cold-induced BAT activity in humans. However, the inverse association between BAT activity and 12α-OH/non-12α-OH ratio may suggest CYP8B1 as a potential new target in BAT function and warrants additional investigation.
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http://dx.doi.org/10.1016/j.mce.2021.111403DOI Listing
October 2021

Functional characterization of adrenocortical masses in nononcological patients using [Ga]-pentixafor.

J Nucl Med 2021 Jul 22. Epub 2021 Jul 22.

The Medical University of Vienna.

We aimed to investigate the diagnostic and prognostic value of Ga-pentixafor positron emission tomography (PET)/computed tomography (CT) imaging in non-cancer patients with suspected adrenal masses. Sixty-four patients who had benign adrenal masses on CT were retrospectively included in our study. All patients underwent Ga-pentixafor PET/CT scans, and 56 of these patients subsequently underwent adrenalectomy. The subtypes of 81 adrenal tumors including 14 nonfunctioning adrenal nodules, 4 cortisol-producing adenomas, 41 aldosterone-producing adenomas, 5 suspected unilateral adrenal hyperplasia, 15 idiopathic aldosterone hyperplasia and 2 pheochromocytomas, were determined by histology or follow-up evaluations. The functional lateralization diagnosis efficiency was calculated by visual analysis. Semi-quantitative parameters of these lesions including maximum standardized uptake value (SUV), the ratio of lesional SUV to normal liver SUVmean (LLR), and the ratio of lesional SUV to contralateral adrenal tissue SUVmean (LCR) have also been calculated. Dynamic analysis has also been performed on fifteen patients. Besides, clinical outcomes were assessed and compared in patients who underwent adrenalectomy. The sensitivity and specificity of Ga-pentixafor PET for functional lateralization of patients with adrenocortical lesions were 97.8% (45/46) and 87.5% (14/16) respectively. The two pheochromocytoma lesions had lower pentixafor uptake compared to the normal adrenal glands. Functioning (active) adrenocortical adenomas showed an elevated SUV of 16.3±7.9 in comparison to 4.4±1.7 in nonfunctioning (inactive) adenomas and 5.5±2.7 in hyperplasia lesions (P<0.0001). To identify active adrenocortical adenomas, a cutoff value of 7.1 for SUV showed a sensitivity of 90.9% and a specificity of 85.3% (AUC=0.96, P<0.0001); a cutoff value of 2.5 for LLR showed a sensitivity of 95.5% and a specificity of 88.2% (AUC=0.97, P<0.0001); and a cutoff value of 2.4 for LCR showed a sensitivity of 88.6% and a specificity of 91.8% (AUC=0.95, P<0.0001). The graphical Ki of active adrenocortical adenomas was significantly higher than in-active adenomas. Uptake values for Ga-pentixafor were significantly higher in patients with preferable outcomes (cured/improved) (SUV=15.5±8.0, LLR=6.5±4.3, LCR=6.2±5.0) than in patients with nonpreferable outcomes (no improvement) (SUV=4.2±0.5, LLR=1.3±0.2, LCR =1.5±0.6, all P<0.0001). Ga-pentixafor PET/CT imaging exhibits great potential for noninvasive functional lateralization and characterization of patients with adrenocortical masses.
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http://dx.doi.org/10.2967/jnumed.121.261964DOI Listing
July 2021

ABCB1 and ABCG2 Together Limit the Distribution of ABCB1/ABCG2 Substrates to the Human Retina and the Single Nucleotide Polymorphism Q141K (c.421C> A) May Lead to Increased Drug Exposure.

Front Pharmacol 2021 16;12:698966. Epub 2021 Jun 16.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, VIE, Austria.

The widely expressed and poly-specific ABC transporters breast cancer resistance protein (ABCG2) and P-glycoprotein (ABCB1) are co-localized at the blood-brain barrier (BBB) and have shown to limit the brain distribution of several clinically used ABCB1/ABCG2 substrate drugs. It is currently not known to which extent these transporters, which are also expressed at the blood-retinal barrier (BRB), may limit drug distribution to the human eye and whether the reduced-function single-nucleotide polymorphism (SNP) Q141K (c.421C > A) has an impact on retinal drug distribution. Ten healthy male volunteers (five subjects with the c.421CC and c.421CA genotype, respectively) underwent two consecutive positron emission tomography (PET) scans after intravenous injection of the model ABCB1/ABCG2 substrate [C]tariquidar. The second PET scan was performed with concurrent intravenous infusion of unlabelled tariquidar to inhibit ABCB1 in order to specifically reveal ABCG2 function.In response to ABCB1 inhibition with unlabelled tariquidar, c.421C > A genotype carriers showed significant increases (as compared to the baseline scan) in retinal radiotracer influx (+62 ± 57%, = 0.043) and volume of distribution (+86 ± 131%, = 0.043), but no significant changes were observed in subjects with the c.421C > C genotype. Our results provide the first evidence that ABCB1 and ABCG2 may together limit the distribution of systemically administered ABCB1/ABCG2 substrate drugs to the human retina. Functional redundancy between ABCB1 and ABCG2 appears to be compromised in carriers of the c.421C > A SNP who may therefore be more susceptible to transporter-mediated drug-drug interactions at the BRB than non-carriers.
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http://dx.doi.org/10.3389/fphar.2021.698966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242189PMC
June 2021

PSMA Expression in 122 Treatment Naive Glioma Patients Related to Tumor Metabolism in C-Methionine PET and Survival.

J Pers Med 2021 Jun 30;11(7). Epub 2021 Jun 30.

Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Apart from its expression in benign and malignant prostate tissue, prostate specific membrane antigen (PSMA) was shown to be expressed specifically in the neovasculature of solid tumors. For gliomas only little information exists. Therefore, we aimed to correlate PSMA expression in gliomas to tumor metabolism by L-[S-methyl-C]methionine (MET) PET and survival. Therefore, immunohistochemical staining (IHC) for isocitrate dehydrogenase 1-R132H (IDH1-R132H) mutation and PSMA expression was performed on the paraffin embedded tissue samples of 122 treatment-naive glioma patients. The IHC results were then related to the pre-therapeutic semiquantitative MET PET data and patients' survival. Vascular PSMA expression was observed in 26 of 122 samples and was rather specific for high-grade gliomas ([HGG] 81% of glioblastoma multiforme, 10% of WHO grade III and just 2% of grade II gliomas). Significantly higher amounts of gliomas without verifiable IDH1-R132H mutation showed vascular PSMA expression. Significantly shorter median survival times were seen for patients with vascular PSMA staining in all tumors as well as HGG only. Additionally, significantly higher numbers of PSMA staining vessels were found in tumors with high amino acid metabolic rates. Vascular PSMA expression in gliomas was seen as a high-grade specific feature associated with elevated amino acid metabolism and short survival.
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http://dx.doi.org/10.3390/jpm11070624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305688PMC
June 2021

Update on PET Tracer Development for Muscarinic Acetylcholine Receptors.

Pharmaceuticals (Basel) 2021 Jun 2;14(6). Epub 2021 Jun 2.

Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, University of Vienna, 1090 Wien, Austria.

The muscarinic cholinergic system regulates peripheral and central nervous system functions, and, thus, their potential as a therapeutic target for several neurodegenerative diseases is undoubted. A clinically applicable positron emission tomography (PET) tracer would facilitate the monitoring of disease progression, elucidate the role of muscarinic acetylcholine receptors (mAChR) in disease development and would aid to clarify the diverse natural functions of mAChR regulation throughout the nervous system, which still are largely unresolved. Still, no mAChR PET tracer has yet found broad clinical application, which demands mAChR tracers with improved imaging properties. This paper reviews strategies of mAChR PET tracer design and summarizes the binding properties and preclinical evaluation of recent mAChR tracer candidates. Furthermore, this work identifies the current major challenges in mAChR PET tracer development and provides a perspective on future developments in this area of research.
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http://dx.doi.org/10.3390/ph14060530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229778PMC
June 2021

Reliability of task-specific neuronal activation assessed with functional PET, ASL and BOLD imaging.

J Cereb Blood Flow Metab 2021 11 2;41(11):2986-2999. Epub 2021 Jun 2.

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.

Mapping the neuronal response during cognitive processing is of crucial importance to gain new insights into human brain function. BOLD imaging and ASL are established MRI methods in this endeavor. Recently, the novel approach of functional PET (fPET) was introduced, enabling absolute quantification of glucose metabolism at rest and during task execution in a single measurement. Here, we report test-retest reliability of fPET in direct comparison to BOLD imaging and ASL. Twenty healthy subjects underwent two PET/MRI measurements, providing estimates of glucose metabolism, cerebral blood flow (CBF) and blood oxygenation. A cognitive task was employed with different levels of difficulty requiring visual-motor coordination. Task-specific neuronal activation was robustly detected with all three imaging approaches. The highest reliability was obtained for glucose metabolism at rest. Although this dropped during task performance it was still comparable to that of CBF. In contrast, BOLD imaging yielded high performance only for qualitative spatial overlap of task effects but not for quantitative comparison. Hence, the combined assessment of fPET and ASL offers reliable and simultaneous absolute quantification of glucose metabolism and CBF at rest and task.
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http://dx.doi.org/10.1177/0271678X211020589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545051PMC
November 2021

Response and Toxicity to the Second Course of 3 Cycles of Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer.

Cancers (Basel) 2021 May 20;13(10). Epub 2021 May 20.

Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, 1090 Vienna, Austria.

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients.

Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87-1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan-Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival.

Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6-1926 µg/L, = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer ( = 0.02), whereas the patients with bone metastases had a shorter survival ( = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS ( < 0.05, hazard ratio 2.43, 95% CI 1.01-5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded.

Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.
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http://dx.doi.org/10.3390/cancers13102489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160614PMC
May 2021

Functional dynamics of dopamine synthesis during monetary reward and punishment processing.

J Cereb Blood Flow Metab 2021 11 30;41(11):2973-2985. Epub 2021 May 30.

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.

The assessment of dopamine release with the PET competition model is thoroughly validated but entails disadvantages for the investigation of cognitive processes. We introduce a novel approach incorporating 6-[F]FDOPA uptake as index of the dynamic regulation of dopamine synthesis enzymes by neuronal firing. The feasibility of this approach is demonstrated by assessing widely described sex differences in dopamine neurotransmission. Reward processing was behaviorally investigated in 36 healthy participants, of whom 16 completed fPET and fMRI during the monetary incentive delay task. A single 50 min fPET acquisition with 6-[F]FDOPA served to quantify task-specific changes in dopamine synthesis. In men monetary gain induced stronger increases in ventral striatum dopamine synthesis than loss. Interestingly, the opposite effect was discovered in women. These changes were further associated with reward (men) and punishment sensitivity (women). As expected, fMRI showed robust task-specific neuronal activation but no sex difference. Our findings provide a neurobiological basis for known behavioral sex differences in reward and punishment processing, with important implications in psychiatric disorders showing sex-specific prevalence, altered reward processing and dopamine signaling. The high temporal resolution and magnitude of task-specific changes make fPET a promising tool to investigate functional neurotransmitter dynamics during cognitive processing and in brain disorders.
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http://dx.doi.org/10.1177/0271678X211019827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543667PMC
November 2021

Dynamic F-FDG PET imaging of liver lesions: evaluation of a two-tissue compartment model with dual blood input function.

BMC Med Imaging 2021 05 25;21(1):90. Epub 2021 May 25.

Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing, People's Republic of China.

Background: Dynamic PET with kinetic modeling was reported to be potentially helpful in the assessment of hepatic malignancy. In this study, a kinetic modeling analysis was performed on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) from dynamic FDG positron emission tomography/computer tomography (PET/CT) scans.

Methods: A reversible two-tissue compartment model with dual blood input function, which takes into consideration the blood supply from both hepatic artery and portal vein, was used for accurate kinetic modeling of liver dynamic F-FDG PET imaging. The blood input functions were directly measured as the mean values over the VOIs on descending aorta and portal vein respectively. And the contribution of hepatic artery to the blood input function was optimization-derived in the process of model fitting. The kinetic model was evaluated using dynamic PET data acquired on 24 patients with identified hepatobiliary malignancy. 38 HCC or ICC identified lesions and 24 healthy liver regions were analyzed.

Results: Results showed significant differences in kinetic parameters [Formula: see text], blood supplying fraction [Formula: see text], and metabolic rate constant [Formula: see text] between malignant lesions and healthy liver tissue. And significant differences were also observed in [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] between HCC and ICC lesions. Further investigations of the effect of SUV measurements on the derived kinetic parameters were conducted. And results showed comparable effectiveness of the kinetic modeling using either SUVmean or SUVmax measurements.

Conclusions: Dynamic 18F-FDG PET imaging with optimization-derived hepatic artery blood supply fraction dual-blood input function kinetic modeling can effectively distinguish malignant lesions from healthy liver tissue, as well as HCC and ICC lesions.
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http://dx.doi.org/10.1186/s12880-021-00623-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152049PMC
May 2021

Diagnostic Role of PET/CT Tracers in the Detection and Localization of Tumours Responsible for Ectopic Cushing's Syndrome.

Anticancer Res 2021 May;41(5):2477-2484

Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.

Background/aim: Positron emission tomography/computed tomography (PET/CT) plays an important role in cancer localization in ectopic Cushing's syndrome (ECS). However, the choice of the optimal tracer for investigation of this disease is still unclear. We aimed to evaluate the diagnostic feasibility of [F]fluoro-2-deoxyglucose ([F]FDG), [F]fluoro-L-dihydroxyphenylalanine ([F] FDOPA), and [Ga]-DOTA-1-Nal3-octreotide ([Ga]-DOTANOC) in ECS.

Patients And Methods: All PET/CT scans of patients admitted to our department for suspected ECS between 2010 and 2020 were retrospectively analysed.

Results: Collectively, 30 PET/CT examinations, 11 with [F]FDOPA, 11 with [F]FDG and 8 with [Ga]GaDOTANOC were conducted for 18 patients eligible for analysis. [F]FDG detected the tumour in 3/6 of the cases, [F]FDOPA in 3/4, and [Ga]GaDOTANOC in 3/3. [F]FDOPA was the only tracer without false positive results.

Conclusion: [Ga]GaDOTANOC and [F]FDOPA showed superior results compared to [F]FDG, although the sensitivity of the tracers might be influenced by the aetiology of the tumour underlying the ECS.
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http://dx.doi.org/10.21873/anticanres.15024DOI Listing
May 2021

Breast Tumor Characterization Using [F]FDG-PET/CT Imaging Combined with Data Preprocessing and Radiomics.

Cancers (Basel) 2021 Mar 12;13(6). Epub 2021 Mar 12.

Division of Molecular and Gender Imaging, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria.

: This study investigated the performance of ensemble learning holomic models for the detection of breast cancer, receptor status, proliferation rate, and molecular subtypes from [F]FDG-PET/CT images with and without incorporating data pre-processing algorithms. Additionally, machine learning (ML) models were compared with conventional data analysis using standard uptake value lesion classification. : A cohort of 170 patients with 173 breast cancer tumors (132 malignant, 38 benign) was examined with [F]FDG-PET/CT. Breast tumors were segmented and radiomic features were extracted following the imaging biomarker standardization initiative (IBSI) guidelines combined with optimized feature extraction. Ensemble learning including five supervised ML algorithms was utilized in a 100-fold Monte Carlo (MC) cross-validation scheme. Data pre-processing methods were incorporated prior to machine learning, including outlier and borderline noisy sample detection, feature selection, and class imbalance correction. Feature importance in each model was assessed by calculating feature occurrence by the R-squared method across MC folds. : Cross validation demonstrated high performance of the cancer detection model (80% sensitivity, 78% specificity, 80% accuracy, 0.81 area under the curve (AUC)), and of the triple negative tumor identification model (85% sensitivity, 78% specificity, 82% accuracy, 0.82 AUC). The individual receptor status and luminal A/B subtype models yielded low performance (0.46-0.68 AUC). SUV model yielded 0.76 AUC in cancer detection and 0.70 AUC in predicting triple negative subtype. : Predictive models based on [F]FDG-PET/CT images in combination with advanced data pre-processing steps aid in breast cancer diagnosis and in ML-based prediction of the aggressive triple negative breast cancer subtype.
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http://dx.doi.org/10.3390/cancers13061249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000810PMC
March 2021

Radiolabeled HER2-directed exosomes exhibit improved cell targeting and specificity.

Nanomedicine (Lond) 2021 03 17;16(7):553-567. Epub 2021 Mar 17.

Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14117-13116, Iran.

Here, we established a reliable strategy for generation and characterization of targeted radiolabeled exosomes for the detection of HER2-positive cells quantitatively. Targeted exosomes (T-exos) were radiolabeled by two different radiotracers, [Tc]Tc-HMPAO or [In]In-oxine. The labeling efficiency and stability were assessed using exosome exclusive spin columns. HER2-positive and -negative cells were treated with [In]In-oxine-exosomes after 3 and 24 h. [In]In-oxine labeling did not change the binding ability and general features of the exosomes. With [In]In-oxine, 70% labeling efficiency and 78% radiochemical stability over 24 h were achieved. [In]In-oxine-T-exos showed greater uptake by HER2-positive cells compared with untargeted exosomes. [In]In-oxine-T-exos could potentially be used as an effective imaging tool for HER2 expression.
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http://dx.doi.org/10.2217/nnm-2020-0408DOI Listing
March 2021

Fluorine-18 fluorodeoxyglucose PET/CT is a suitable instrument to show the effects of lipid metabolism disorders on metabolic networks in the living organism.

J Nucl Cardiol 2021 Feb 24. Epub 2021 Feb 24.

Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

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http://dx.doi.org/10.1007/s12350-021-02543-8DOI Listing
February 2021

Standard MRI-based attenuation correction for PET/MRI phantoms: a novel concept using MRI-visible polymer.

EJNMMI Phys 2021 Feb 18;8(1):18. Epub 2021 Feb 18.

QIMP Team, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20/4L, 1090, Vienna, Austria.

Background: PET/MRI phantom studies are challenged by the need of phantom-specific attenuation templates to account for attenuation properties of the phantom material. We present a PET/MRI phantom built from MRI-visible material for which attenuation correction (AC) can be performed using the standard MRI-based AC.

Methods: A water-fillable phantom was 3D-printed with a commercially available MRI-visible polymer. The phantom had a cylindrical shape and the fillable compartment consisted of a homogeneous region and a region containing solid rods of different diameters. The phantom was filled with a solution of water and [18F]FDG. A 30 min PET/MRI acquisition including the standard Dixon-based MR-AC method was performed. In addition, a CT scan of the phantom was acquired on a PET/CT system. From the Dixon in-phase, opposed-phase and fat images, a phantom-specific AC map (Phantom MR-AC) was produced by separating the phantom material from the water compartment using a thresholding-based method and assigning fixed attenuation coefficients to the individual compartments. The PET data was reconstructed using the Phantom MR-AC, the original Dixon MR-AC, and an MR-AC just containing the water compartment (NoWall-AC) to estimate the error of ignoring the phantom walls. CT-based AC was employed as the reference standard. Average %-differences in measured activity between the CT corrected PET and the PET corrected with the other AC methods were calculated.

Results: The phantom housing and the liquid compartment were both visible and distinguishable from each other in the Dixon images and allowed the segmentation of a phantom-specific MR-based AC. Compared to the CT-AC PET, average differences in measured activity in the whole water compartment in the phantom of -0.3%, 9.4%, and -24.1% were found for Dixon phantom MR-AC, MR-AC, and NoWall-AC based PET, respectively. Average differences near the phantom wall in the homogeneous region were -0.3%, 6.6%, and -34.3%, respectively. Around the rods, activity differed from the CT-AC PET by 0.7%, 8.9%, and -45.5%, respectively.

Conclusion: The presented phantom material is visible using standard MR sequences, and thus, supports the use of standard, phantom-independent MR measurements for MR-AC in PET/MRI phantom studies.
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http://dx.doi.org/10.1186/s40658-021-00364-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892652PMC
February 2021
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