Alessio Imperiale

18F-Fluorodihydroxyphenylalanine PET/CT in Patients with Neuroendocrine Tumors of Unknown Origin: Relation to Tumor Origin and Differentiation

This work was performed to evaluate the performance of 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT in detecting primary neuroendocrine tumors (NETs) occult on morphologic and functional imaging, in relation to tumor origin and differentiation. Methods: A retrospective study of NET patients who were investigated with 18F-FDOPA PET/CT imaging in 2 academic endocrine tumor centers was conducted. Only patients with negative conventional and somatostatin receptor scintigraphy (SRS) results were studied. Results: Twenty-seven patients were evaluated with 18F-FDOPA PET/CT, 23 at their initial staging and 4 during their follow-up. The primary occult NET was localized by 18F-FDOPA PET/CT in 12 patients (overall sensitivity, 44%; 52% in patients evaluated at initial diagnosis), leading to tumor resection in all cases. The primary tumors were distributed and graded as follows: 1 duodenum G2 lesion, 7 ileum G2 lesions, 2 terminal ileum G1 lesions, 1 pancreas G2 lesion, and 1 gallbladder G3 lesion. Patients with positive 18F-FDOPA PET/CT results had higher values of serum chromogranin A (100% vs. 20%, P = 0.0003), serotonin, or urinary 5-hydroxyindolacetic acid (83% vs. 20%, P = 0.003). Two false-negative results were related to poorly differentiated duodenal and prostatic NETs (G3). 18F-FDOPA PET/CT showed more metastatic anatomic regions than SRS in 17 patients. Conclusion: 18F-FDOPA PET appears to be a sensitive functional imaging tool for the detection of primary NETs occult on SRS, especially tumors with a well-differentiated pattern and serotonin secretion.

On nuclear spectrometry pulses digital shaping and processing

Trapezoidal pulse shaping by a digital technique from nuclear spectrometry preamplifier output is reported. The shaping is especially suitable for time and/or pulse-height spectra measurements from high counting rate sources which commonly implies pulse pile up. In fact, piled up events may be identified and measured rather than rejected as in usual analog systems. Moreover, the amplitude-arrival time measurement of piled up pulses by the trapezoidal shape is simpler than by both maximum likelihood and least squares estimators, or adaptive nonlinear least squares methods which give better results in the case of severe pile up. Comparison with different techniques currently used in fast scanners for nuclear medicine studies is given. The technique utility in high energy semiconductor gamma ray spectrometry is also discussed.

Osteoblastoma and osteoid osteoma: morphofunctional characterization by MRI and dynamic F-18 FDG PET/CT before and after radiofrequency ablation.

Osteoblastoma (OB) and osteoid osteoma (OO) are benign bone-forming tumors frequently involving vertebrae and long bones of the extremities. Because of their similar histopathological features, distinction between OB and OO is mostly based on size criteria. CT and MRI represent the cornerstone of noninvasive diagnostic procedures, as they provide excellent morphologic details and often obviate the need for confirmatory biopsy. Bone scan is a complementary, highly sensitive functional technique particularly useful for detection of vertebral OO. F-18 FDG PET/CT could have potentiality in diagnosis and post therapeutic evaluation of patients with OB and OO. We report MRI and dynamic F-18 FDG PET/CT results obtained before radiofrequency or laser ablation from 3 patients with an OB of the right L5 pedicle, an OB of the left talus and an OO of the right acetabulum. Both patients with OB underwent posttherapeutic evaluation to confirm the effectiveness of percutaneous radiofrequency ablation.

Metabolome profiling by HRMAS NMR spectroscopy of pheochromocytomas and paragangliomas detects SDH deficiency: clinical and pathophysiological implications.

Succinate dehydrogenase gene (SDHx) mutations increase susceptibility to develop pheochromocytomas/paragangliomas (PHEOs/PGLs). In the present study, we evaluate the performance and clinical applications of 1H high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy–based global metabolomic profiling in a large series of PHEOs/PGLs of different genetic backgrounds. Eighty-seven PHEOs/PGLs (48 sporadic/23 SDHx/7 von Hippel-Lindau/5 REarranged during Transfection/3 neurofibromatosis type 1/1 hypoxia-inducible factor 2α), one SDHD variant of unknown significance, and two Carney triad (CTr)–related tumors were analyzed by HRMAS-NMR spectroscopy. Compared to sporadic, SDHx-related PHEOs/PGLs exhibit a specific metabolic signature characterized by increased levels of succinate (P < .0001), methionine (P = .002), glutamine (P = .002), and myoinositol (P < .0007) and decreased levels of glutamate (P < .0007), regardless of their location and catecholamine levels. Uniquely, ATP/ascorbate/glutathione was found to be associated with the secretory phenotype of PHEOs/PGLs, regardless of their genotype (P < .0007). The use of succinate as a single screening test retained excellent accuracy in distinguishing SDHx versus non–SDHx-related tumors (sensitivity/specificity: 100/100%). Moreover, the quantification of succinate could be considered a diagnostic alternative for assessing SDHx-related mutations of unknown pathogenicity. We were also able, for the first time, to uncover an SDH-like pattern in the two CTr-related PGLs. The present study demonstrates that HRMAS-NMR provides important information for SDHx-related PHEO/PGL characterization. Besides the high succinate–low glutamate hallmark, SDHx tumors also exhibit high values of methionine, a finding consistent with the hypermethylation pattern of these tumors. We also found important levels of glutamine, suggesting that glutamine metabolism might be involved in the pathogenesis of SDHx-related PHEOs/PGLs.

F-18 FDG PET/CT as a valuable imaging tool for assessing treatment efficacy in inflammatory and infectious diseases.

Activated inflammatory cells like neutrophils, macrophages, and lymphocytes have increased F-18 FDG uptake, causing significant tracer accumulation in inflammatory and infectious processes. In this report, we have illustrated F-18 FDG PET/CT features related to systemic sarcoidosis, large-vessel arteritis, abdominal tuberculosis, and pleural aspergillosis in 4 selected patients, who underwent scintigraphic evaluation before and after anti-inflammatory or antibiotic treatment. The evolution of radiotracer uptake intensity reflected the efficacy of medical treatment, permitting either a better modulation of drug dosage or a radical modification of therapeutic strategy. Independently from the cost and access to this type of medical imaging, F-18 FDG PET/CT could have a potential role in assessing treatment efficacy in selected non-neoplastic conditions, allowing morphofunctional cartography of residual inflammatory localizations.

Transient left ventricular dysfunction syndrome during anaphylactic shock: Vasospasm, Kounis syndrome or epinephrine-induced stunned myocardium?

Abstract Transient left ventricular dysfunction syndrome (TVLDS) has been rarely observed during anaphylactic shock and its pathophysiology remains still enigmatic. Multivessel epiicardial coronary spasm or coronary microvascular impairment were suggested as primary causative mechanism. Alternatively, the release of various inflammatory mediators including histamine could induce a coronary artery spasm or erosion/rupture of an atheromatous plaque contributing to TLVDS. Challenging this paradigm, a direct catecholamine acute toxicity was recently proposed as a causative mechanism of the stunned myocardium observed in TLVDS. We report a patient with severe TLVDS during anaphylactic shock. Whilst ECG depicted a drastic ST segment elevation in the anterior leads, cardiac catheterism confirms the co-existence of severe reduction of systemic vascular resistance and normal coronary angiogram. In the absence of any documented spasm or perfusion abnormalities, the defective uptake of 123 I-metaiodobenzyl-guanidine ( 123 I-mIBG) in the hypocontractile LV segments suggests that epinephrine-induced stunned myocardium is the main mechanism of LV systolic dysfunction. This report highlights that excess doses of epinephrine might contribute to TLVDS through direct myocardial stunning. The possible noxious contribution of other mediators such as histamine or cytokines released in the Kounis syndrome remains to be established.

Molecular Imaging of Gastroenteropancreatic Neuroendocrine Tumors: Current Status and Future Directions

Through diagnostic imaging and peptide receptor radionuclide therapy, nuclear medicine has earned a major role in gastroenteropancreatic neuroendocrine tumors (GEP NETs). GEP NETs are diagnosed fortuitously or on the basis of symptoms or hormonal syndrome. The functional tumor characteristics shown by radionuclide imaging allow for more accurate staging and treatment selection. Tumor grade helps determine which tracer should be selected. In the past, 111In-pentetreotide has been successful in well-differentiated (G1 and G2) tumors. However, PET/CT imaging with novel somatostatin analogs (e.g., 68Ga-DOTATOC, 68Ga-DOTATATE, 68Ga-DOTANOC, and 64Cu-DOTATATE) now offers improved sensitivity. 18F-fluorodihydroxyphenylalanine (18F-FDOPA) is another interesting radiopharmaceutical. 18F-FDOPA sensitivity is influenced by a tumor’s capacity to take up, decarboxylate, and store amine precursors. 18F-FDOPA sensitivities are highest in ileal NETs and may also be helpful in insulinomas. A high uptake of 18F-FDG with a low uptake of somatostatin analog usually indicates poorly differentiated tumors (G3). Starting from these principles, this article discusses theranostic approaches to GEP NETs, taking into account both primary and metastatic lesions.

Metabolomic pattern of childhood neuroblastoma obtained by 1H-high-resolution magic angle spinning (HRMAS) NMR spectroscopy†

The aim of this preliminary study is to characterize by 1H high‐resolution magic angle spinning NMR spectroscopy (HRMAS) the metabolic content of intact biopsy samples obtained from 12 patients suffering from neuroblastoma (NB).

Magnetic resonance spectroscopy of paragangliomas: new insights into in vivo metabolomics

Paragangliomas (PGLs) can be associated with mutations in genes of the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase (SDHx) mutations are the prime examples of genetically determined TCA cycle defects with accumulation of succinate. Succinate, which acts as an oncometabolite, can be detected by ex vivo metabolomics approaches. The aim of this study was to evaluate the potential role of proton magnetic resonance (MR) spectroscopy ((1)H-MRS) for identifying SDHx-related PGLs in vivo and noninvasively. Eight patients were prospectively evaluated with single voxel (1)H-MRS. MR spectra from eight tumors (four SDHx-related PGLs, two sporadic PGLs, one cervical schwannoma, and one cervical neurofibroma) were acquired and interpreted qualitatively. Compared to other tumors, a succinate resonance peak was detected only in SDHx-related tumor patients. Spectra quality was considered good in three cases, medium in two cases, poor in two cases, and uninterpretable in the latter case. Smaller lesions had lower spectra quality compared to larger lesions. Jugular PGLs also exhibited a poorer spectra quality compared to other locations. (1)H-MRS has always been challenging in terms of its technical requisites. This is even more true for the evaluation of head and neck tumors. However, (1)H-MRS might be added to the classical MR sequences for metabolomic characterization of PGLs. In vivo detection of succinate might guide genetic testing, characterize SDHx variants of unknown significance (in the absence of available tumor sample), and even optimize a selection of appropriate therapies.

Impact of Malignancies in the Early and Late Time Course of Takotsubo Cardiomyopathy

BACKGROUND Although the relationship between malignancies and catecholamine-induced myocardial stunning remains largely speculative, it has been suggested that the presence of cancer may lower the threshold for stress stimuli and/or may aggravate cardiac adrenoreceptor sensitivity. We sought to investigate whether associations exist between a previous or current diagnosis of malignancy, diagnostic parameters during hospitalization and death in takotsubo. METHODSANDRESULTS The 154 takotsubo patients were retrospectively identified between May 2008 and December 2014. Previous history of malignancy was identified in 44 patients (28.5%). Cardiac arrest was present at admission in 13 patients (8.4%). Intra-aortic balloon pump was inserted in 16 patients (10.4%). In patients with malignancy, higher B-type natriuretic peptide (BNP), leukocyte and C-reactive protein (CRP) peaks could be observed during the hospital phase. Initial impairment of left ventricular ejection fraction was negatively related to BNP, leukocyte, and CRP peaks. At a median follow-up of 364 days, all-cause death occurred in 41 patients (26.6%) and cardiac death in 12 patients (7.7%). Multivariate Cox regression analysis identified malignancy (hazard ratio 4.77 (1.02-22.17), leukocyte peak and age as independent predictors of cardiac death. Malignancy (2.62 (1.26-5.44), leukocyte peak (1.05 (1.01-1.08) and initial cardiac arrest (6.68 (2.47-18.01) were identified as independent predictors of overall mortality. CONCLUSIONS In the present takotsubo patients, the prevalence of malignancy was high and may have affected cardiovascular outcomes through the activation of inflammatory and neurohormonal mechanisms. (Circ J 2016; 80: 2192-2198).