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2.
Ann Neurol ; 95(6): 1178-1192, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38466158

RESUMEN

OBJECTIVE: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. RESULTS: Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters. INTERPRETATION: Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178-1192.


Asunto(s)
Dopamina , Enfermedad por Cuerpos de Lewy , Aprendizaje Automático , Enfermedad de Parkinson , Trastorno de la Conducta del Sueño REM , Sinucleinopatías , Humanos , Trastorno de la Conducta del Sueño REM/diagnóstico por imagen , Masculino , Femenino , Anciano , Sinucleinopatías/diagnóstico por imagen , Persona de Mediana Edad , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/complicaciones , Dopamina/metabolismo , Tomografía Computarizada de Emisión de Fotón Único , Terminales Presinápticos/metabolismo , Imágenes Dopaminérgicas
3.
Curr Probl Cancer ; 47(6): 101007, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37684197

RESUMEN

The last version of the FIGO classification recommended imaging tools to complete the clinical assessment of patients with cervical cancer. However, the preferable imaging approach is still unclear. We aimed to explore the prognostic power of Magnetic Resonance Imaging (MRI), contrast-enhanced Computed Tomography (ceCT), and [18F]-Fluorodeoxyglucose Positron Emission Tomography ([18F]FDG-PET)/CT in patients staged for locally advanced cervical cancer (LACC, FIGO stages IB3-IVA). Thirty-six LACC patients (mean age 55.47 ± 14.01, range 31-82) were retrospectively enrolled. All of them underwent MRI, ceCT and [18F]FDG-PET/CT before receiving concurrent chemoradiotherapy. A median dose of 45 Gy (range 42-50.4; 25-28 fractions, 5 fractions per week, 1 per day) was delivered through the external-beam radiation therapy (EBRT) on the pelvic area, while a median dose of 57.5 Gy (range 16-61.1; 25-28 fractions, 5 fractions per week, 1 per day) was administered on metastatic nodes. The median doses for brachytherapy treatment were 28 Gy (range 28-30; 4-5 fractions, 1 every other day). Six cycles of cisplatin or carboplatin were administered weekly. The study endpoints were recurrence-free survival (RFS) and overall survival (OS). Metastatic pelvic lymph nodes at MRI independently predicted RFS (HR 13.271, 95% CI 1.730-101.805; P = 0.027), while metastatic paraaortic lymph nodes at [18F]FDG-PET/CT independently predicted both RFS (HR 11.734, 95% CI 3.200-43.026; P = .005) and OS (HR 13.799, 95% CI 3.378-56.361; P < 0.001). MRI and [18F]FDG-PET/CT findings were incorporated with clinical evidences into the FIGO classification. With respect to the combination of clinical, MRI and ceCT data, the use of next-generation imaging (NGI) determined a stage migration in 10/36 (27.7%) of patients. Different NGI-based FIGO classes showed remarkably different median RFS (stage IIB: not reached; stage IIIC1: 44 months; stage IIIC2: 3 months; P < 0.001) and OS (stage IIB: not reached; stage IIIC1: not reached; stage IIIC2: 14 months; P < 0.001). A FIGO classification based on the combination of MRI and [18F]FDG-PET/CT might predict RFS and OS of LACC patients treated with concurrent chemoradiotherapy.


Asunto(s)
Fluorodesoxiglucosa F18 , Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Pronóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/terapia , Radiofármacos , Estudios Retrospectivos , Tomografía de Emisión de Positrones , Quimioradioterapia/efectos adversos , Imagen por Resonancia Magnética , Estadificación de Neoplasias
4.
Cancers (Basel) ; 15(13)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37444643

RESUMEN

BACKGROUND: Previous studies reported mitochondrial and endoplasmic reticulum redox stress in peripheral blood mononucleated cells (PBMCs) of treatment-naïve Hodgkin lymphoma (HL) patients. Here, we assessed whether this response also applies to non-HL (NHL) patients, and whether the oxidative damage is a selective feature of PBMCs or, rather, also affects tissues not directly involved in the inflammatory response. METHODS: Isolated PBMCs of 28 HL, 9 diffuse large B cell lymphoma, 8 less aggressive-NHL, and 45 controls underwent flow cytometry to evaluate redox stress and uptake of the glucose analogue 2-NBDG. This analysis was complemented with the assay of malondialdehyde (MDA) levels and enzymatic activity of glucose-6P-dehydrogenase and hexose-6P-dehydrogenase (H6PD). In all lymphoma patients, 18F-fluoro-deoxyglucose uptake was estimated in the myocardium and skeletal muscles. RESULTS: Mitochondrial reactive oxygen species generation and MDA levels were increased only in HL patients as well as H6PD activity and 2-NBDG uptake. Similarly, myocardial FDG retention was higher in HL than in other groups as opposed to a similar tracer uptake in the skeletal muscle. CONCLUSIONS: Redox stress of PBMCs is more pronounced in HL with respect to both NHL groups. This phenomenon is coherent with an increased activity of H6PD that also extends to the myocardium.

5.
Eur J Clin Invest ; 53(9): e14011, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37099603

RESUMEN

BACKGROUND: This study aimed to estimate if the altered sphygmic wave transmission may affect the left ventricular (LV) contractile function in patients undergoing endovascular aortic repair (EVAR). METHODS: A prospective single-centre study was carried out on consecutive patients undergoing EVAR for abdominal aortic aneurysm. A preoperative and 6-month single photon emission computed tomography (SPECT) with arterial stiffness measurement were performed to evaluate variations in pressure wave curve and myocardial perfusion parameters. RESULTS: From 2018 to 2020 a total of 16 patients were included in the study. Among the parameters evaluated, we found a measurable reduction of the reflected wave transit time from pre- to postoperative period, for both stress (115.13 ± 7.2 ms-111.1 ± 7.0 ms, p = .08) and rest SPECT acquisitions (115.3 ± 6.2 ms-112.2 ± 5.6 ms, p = .1). Unidirectional increase of both LV end-systolic volume (34 ± 9 mL-39 ± 8 mL, p = .02) and end-diastolic volume (85 ± 34 mL-89 ± 29 mL, p = .6) was also observed. Lastly, the ratio between the end-systolic pressure and the end-systolic volume (maximal systolic myocardial stiffness) decreased from 3.6 ± 1.5 mmHg/mL to 2.66 ± .74 mmHg/mL (p = .03). CONCLUSIONS: Our data showed that EVAR induced an altered transmission of the sphygmic wave associated with an early LV contractile impairment.


Asunto(s)
Aneurisma de la Aorta Abdominal , Disfunción Ventricular Izquierda , Humanos , Estudios Prospectivos , Reparación Endovascular de Aneurismas , Función Ventricular Izquierda , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía
6.
Eur J Nucl Med Mol Imaging ; 50(4): 1090-1102, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36471041

RESUMEN

PURPOSE: A cut-off of -2 z-score for striatal or putaminal SBR has been to date arbitrarily used to define an abnormal DaT SPECT in patients with suspected neurodegenerative parkinsonism. We aimed to experimentally identify the most accurate z-score cut-offs for SBR of striatal and substriatal regions to independently discriminate PD and DLB, with respect to essential tremor (ET) and Alzheimer's disease (AD) respectively. METHODS: Two-hundred twenty-five patients undergoing DaT SPECT were enrolled (seventy-five de novo PD, eighty ET, fifty DLB, and twenty AD). Semiquantification was computed by means of Datquant® software which returns measures of striatal SBR and z-scores with respect to 118 healthy volunteers belonging to the Parkinson's Progression Markers Initiative (PPMI). ROC analysis was used to identify most accurate cut-offs for z-score for striatum and substriatal regions (clinical diagnosis at follow-up as gold standard). RESULTS: Posterior putamen of the most affected hemisphere (MAH) with a z-score cut-off of - 1.27 demonstrated the highest accuracy to differentiate between PD and ET (sensitivity 0.97, specificity 0.94). The whole putamen (z-score cut-off - 0.96) was the most accurate parameter to support the diagnosis of DLB (sensitivity 0.74, specificity 0.95). Putamen to caudate ratio was accurate to detect PD (especially in early stages) while not DLB patients. CONCLUSION: We experimentally demonstrated that different substriatal regions and cut-offs for z-score of SBR should be considered to support the diagnosis of either PD or DLB. The identified less conservative cut-offs showed higher sensitivity without a measurable reduction in specificity with respect to the arbitrary - 2 z-score.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad por Cuerpos de Lewy , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/metabolismo , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo
7.
Diagnostics (Basel) ; 12(3)2022 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-35328134

RESUMEN

The role of 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in the management of prostate cancer (PCa) patients is increasingly recognised. However, its clinical role is still controversial. Many published studies showed that FDG PET/CT might have a prognostic value in the metastatic castration-resistant phase of the disease, but its role in other settings of PCa and, more importantly, its impact on final clinical management remains to be further investigated. We describe a series of six representative clinical cases of PCa in different clinical settings, but all characterised by a measurable clinical impact of FDG PET/CT on the patients' management. Starting from their clinical history, we report a concise narrative literature review on the advantages and limitations of FDG PET/CT beyond its prognostic value in PCa. What emerges is that in selected cases, this imaging technique may represent a useful tool in managing PCa patients. However, in the absence of dedicated studies to define the optimal clinical setting of its application, no standard recommendations on its use in PCa patients can be made.

8.
Diagnostics (Basel) ; 12(2)2022 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-35204596

RESUMEN

Purpose To evaluate the role of 2-[18F]FDGPET/CT in the follow-up of radioiodine refractory thyroid cancer (RR-TC). Methods Forty-six 2-[18F]FDGPET/CT scans from 14 RR-TC patients were considered. Thyroid function tests: thyroglobulin (Tg), levothyroxine (LT4), and tyrosine-kinases inhibitors (TKIs) assumptions were recorded. Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated from each scan and correlated with clinical parameters and the overall survival (OS). Results Baseline TLG and MTV predicted OS (p = 0.027 and p = 0.035), and negative correlation with OS was also confirmed when the same parameters were measured in follow-up scans (p = 0.015 and p = 0.021). Tg also correlated with the OS; (p = 0.014; p = 0.019 and p = 0.009). However, TLG and MTV were not significantly correlated with Tg levels. MTV and TLG variation in time were reduced during TKI therapy (p = 0.045 and p = 0.013). Conclusions 2-[18F]FDGPET/CT confirmed its prognostic role at the first assessment and during the follow-up of RR-TC patients. 2-[18F]FDGPET/CT parameters seem at least partially independent from Tg. TKI therapy resulted in a measurable effect on the variation of 2-[18F]FDGPET/CT parameters over time.

9.
Ann Nucl Med ; 36(4): 373-383, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35044592

RESUMEN

OBJECTIVE: Androgen deprivation therapy alters body composition promoting a significant loss in skeletal muscle (SM) mass through inflammation and oxidative damage. We verified whether SM anthropometric composition and metabolism are associated with unfavourable overall survival (OS) in a retrospective cohort of metastatic castration-resistant prostate cancer (mCRPC) patients submitted to 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) imaging before receiving Radium-223. PATIENTS AND METHODS: Low-dose CT were opportunistically analysed using a cross-sectional approach to calculate SM and adipose tissue areas at the third lumbar vertebra level. Moreover, a 3D computational method was used to extract psoas muscles to evaluate their volume, Hounsfield Units (HU) and FDG retention estimated by the standardized uptake value (SUV). Baseline established clinical, lab and imaging prognosticators were also recorded. RESULTS: SM area predicted OS at univariate analysis. However, this capability was not additive to the power of mean HU and maximum SUV of psoas muscles volume. These factors were thus combined in the Attenuation Metabolic Index (AMI) whose power was tested in a novel uni- and multivariable model. While Prostate-Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase and Hemoglobin, Metabolic Tumor Volume, Total Lesion Glycolysis and AMI were associated with long-term OS at the univariate analyses, only PSA, ALP and AMI resulted in independent prognosticator at the multivariate analysis. CONCLUSION: The present data suggest that assessing individual 'patients' SM metrics through an opportunistic operator-independent computational analysis of FDG PET/CT imaging provides prognostic insights in mCRPC patients candidates to receive Radium-223.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Antagonistas de Andrógenos/uso terapéutico , Benchmarking , Fluorodesoxiglucosa F18 , Humanos , Masculino , Músculo Esquelético/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Radio (Elemento)/uso terapéutico , Estudios Retrospectivos
10.
Mov Disord ; 37(1): 52-61, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34533239

RESUMEN

BACKGROUND: Dopamine transporter single photon-emission computed tomography (DAT-SPECT) is the strongest risk factor for phenoconversion in patients with idiopathic rapid eye movement (REM)-sleep behavior disorder (iRBD). However, it might be used as a second-line stratification tool in clinical trials, because it is expensive and mini-invasive. OBJECTIVE: Aim of the study is to investigate whether other cost-effective and non-invasive biomarkers may be proposed as first-line stratification tools. METHODS: Forty-seven consecutive iRBD patients (68.53 ± 7.16 years, 40 males) underwent baseline clinical and neuropsychological assessment, olfaction test, resting electroencephalogram (EEG), and DAT-SPECT. All patients underwent 6 month-based clinical follow-up to investigate the emergence of parkinsonism and/or dementia. Survival analysis and Cox regression were used to estimate conversion risk. RESULTS: Seventeen patients developed an overt synucleinopathy (eight Parkinsonism and nine dementia) 32.8 ± 22 months after diagnosis. The strongest risk factors were putamen specific to non-displaceable binding ratio (SBR) (hazard ratio [HR], 7.3), attention/working memory cognitive function (NPS-AT/WM) (HR, 5.9), EEG occipital mean frequency (HR, 2.7) and clinical motor assessment (HR, 2.3). On multivariate Cox-regression analysis, only putamen SBR and NPS-AT/WM significantly contributed to the model (HR, 6.2, 95% confidence interval [CI], 1.9-19.8). At post-hoc analysis, the trail-making test B (TMT-B) was the single most efficient first-line stratification tool that allowed to reduce the number of eligible subjects to 76.6% (sensitivity 1, specificity 0.37). Combining TMT-B and DAT-SPECT further reduced the sample to 66% (sensitivity 0.88, specificity 0.47). CONCLUSION: The TMT-B seems to be a cost-effective and efficient first-line screening tool, to be used to select patients that deserve DAT-SPECT as second-line screening tool for disease-modifying clinical trials. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Asunto(s)
Trastornos Parkinsonianos , Trastorno de la Conducta del Sueño REM , Sinucleinopatías , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Putamen/metabolismo , Trastorno de la Conducta del Sueño REM/metabolismo , Tomografía Computarizada de Emisión de Fotón Único
11.
Eur J Nucl Med Mol Imaging ; 49(4): 1263-1274, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34651219

RESUMEN

PURPOSE: FDG-PET is an established supportive biomarker in dementia with Lewy bodies (DLB), but its diagnostic accuracy is unknown at the mild cognitive impairment (MCI-LB) stage when the typical metabolic pattern may be difficultly recognized at the individual level. Semiquantitative analysis of scans could enhance accuracy especially in less skilled readers, but its added role with respect to visual assessment in MCI-LB is still unknown. METHODS: We assessed the diagnostic accuracy of visual assessment of FDG-PET by six expert readers, blind to diagnosis, in discriminating two matched groups of patients (40 with prodromal AD (MCI-AD) and 39 with MCI-LB), both confirmed by in vivo biomarkers. Readers were provided in a stepwise fashion with (i) maps obtained by the univariate single-subject voxel-based analysis (VBA) with respect to a control group of 40 age- and sex-matched healthy subjects, and (ii) individual odds ratio (OR) plots obtained by the volumetric regions of interest (VROI) semiquantitative analysis of the two main hypometabolic clusters deriving from the comparison of MCI-AD and MCI-LB groups in the two directions, respectively. RESULTS: Mean diagnostic accuracy of visual assessment was 76.8 ± 5.0% and did not significantly benefit from adding the univariate VBA map reading (77.4 ± 8.3%) whereas VROI-derived OR plot reading significantly increased both accuracy (89.7 ± 2.3%) and inter-rater reliability (ICC 0.97 [0.96-0.98]), regardless of the readers' expertise. CONCLUSION: Conventional visual reading of FDG-PET is moderately accurate in distinguishing between MCI-LB and MCI-AD, and is not significantly improved by univariate single-subject VBA but by a VROI analysis built on macro-regions, allowing for high accuracy independent of reader skills.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad por Cuerpos de Lewy , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Disfunción Cognitiva/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/metabolismo , Tomografía de Emisión de Positrones/métodos , Reproducibilidad de los Resultados
12.
Nucl Med Mol Imaging ; 55(6): 323-324, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34868383

RESUMEN

We describe the case of an 82-year-old man who underwent 68 Ga-prostate-specific membrane antigen-11 (68 Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) for the restaging of prostate carcinoma. 68 Ga-PSMA-11 PET/CT unexpectedly showed increased tracer uptake homogenously involving the axial and appendicular bone marrow and the spleen, not characteristic for metastatic prostate disease. Further investigations revealed that 2 months before the patient underwent bone marrow biopsy, which showed the occurrence of monolinear myelodysplasia.

13.
Antioxidants (Basel) ; 10(9)2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34573024

RESUMEN

Recent studies reported that the uptake of [18F]-fluorodeoxyglucose (FDG) is increased in the spinal cord (SC) and decreased in the motor cortex (MC) of patients with ALS, suggesting that the disease might differently affect the two nervous districts with different time sequence or with different mechanisms. Here we show that MC and SC astrocytes harvested from newborn B6SJL-Tg (SOD1G93A) 1Gur mice could play different roles in the pathogenesis of the disease. Spectrophotometric and cytofluorimetric analyses showed an increase in redox stress, a decrease in antioxidant capacity and a relative mitochondria respiratory uncoupling in MC SOD1G93A astrocytes. By contrast, SC mutated cells showed a higher endurance against oxidative damage, through the increase in antioxidant defense, and a preserved respiratory function. FDG uptake reproduced the metabolic response observed in ALS patients: SOD1G93A mutation caused a selective enhancement in tracer retention only in mutated SC astrocytes, matching the activity of the reticular pentose phosphate pathway and, thus, of hexose-6P dehydrogenase. Finally, both MC and SC mutated astrocytes were characterized by an impressive ultrastructural enlargement of the endoplasmic reticulum (ER) and impairment in ER-mitochondria networking, more evident in mutated MC than in SC cells. Thus, SOD1G93A mutation differently impaired MC and SC astrocyte biology in a very early stage of life.

14.
Biomolecules ; 11(8)2021 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-34439897

RESUMEN

Several studies reported that metformin, the most widely used drug for type 2 diabetes, might affect cancer aggressiveness. The biguanide seems to directly impair cancer energy asset, with the consequent phosphorylation of AMP-activated protein kinase (AMPK) inhibiting cell proliferation and tumor growth. This action is most often attributed to a well-documented blockage of oxidative phosphorylation (OXPHOS) caused by a direct interference of metformin on Complex I function. Nevertheless, several other pleiotropic actions seem to contribute to the anticancer potential of this biguanide. In particular, in vitro and in vivo experimental studies recently documented that metformin selectively inhibits the uptake of 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG), via an impaired catalytic function of the enzyme hexose-6P-dehydrogenase (H6PD). H6PD triggers a still largely uncharacterized pentose-phosphate pathway (PPP) within the endoplasmic reticulum (ER) that has been found to play a pivotal role in feeding the NADPH reductive power for both cellular proliferation and antioxidant responses. Regardless of its exploitability in the clinical setting, this metformin action might configure the ER metabolism as a potential target for innovative therapeutic strategies in patients with solid cancers and potentially modifies the current interpretative model of FDG uptake, attributing PET/CT capability to predict cancer aggressiveness to the activation of H6PD catalytic function.


Asunto(s)
Glucosa/metabolismo , Metformina/metabolismo , Neoplasias/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Investigación Biomédica , Deshidrogenasas de Carbohidratos/metabolismo , Proliferación Celular , Citosol/metabolismo , Retículo Endoplásmico/metabolismo , Fluorodesoxiglucosa F18 , Humanos , Hipoglucemiantes/metabolismo , NADP/metabolismo , Fosforilación Oxidativa , Vía de Pentosa Fosfato , Fosforilación , Tomografía Computarizada por Tomografía de Emisión de Positrones , Reproducibilidad de los Resultados
15.
Cancers (Basel) ; 13(13)2021 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-34206545

RESUMEN

An emerging clinical need is represented by identifying reliable biomarkers able to discriminate between responders and non-responders among patients showing imaging progression during the administration of immune checkpoints inhibitors for advanced non-small cell lung cancer (NSCLC). In the present study, we analyzed the prognostic power of peripheral-blood systemic inflammation indexes and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this clinical setting. In 45 patients showing radiological progression (defined as RECIST 1.1 progressive disease) during Nivolumab administration, the following lab and imaging parameters were collected: neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), systemic inflammation index (SII), maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). MTV and SII independently predicted OS. Their combination in the immune metabolic prognostic index (IMPI) allowed the identification of patients who might benefit from immunotherapy continuation, despite radiological progression. The combination of FDG PET/CT volumetric data with SII also approximates the immune-metabolic response with respect to baseline, providing additional independent prognostic insights. In conclusion, the degree of systemic inflammation, the quantification of the metabolically active tumor burden, and their combination might disclose the radiological progression in NSCLC patients receiving Nivolumab.

16.
Eur J Radiol ; 140: 109737, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33951567

RESUMEN

Musculoskeletal (MSK) pathologies are one of the leading causes of disability worldwide. However, treatment options and understanding of pathogenetic processes are still partially unclear, mainly due to a limited ability in early disease detection and response to therapy assessment. In this scenario, thanks to a strong technological advancement, structural imaging is currently established as the gold-standard of diagnosis in many MSK disorders but each single diagnostic modality (plain films, high-resolution ultrasound, computed tomography and magnetic resonance) still suffer by a low specificity regarding the characterization of inflammatory processes, the quantification of inflammatory activity levels, and the degree of response to therapy. To overcome these limitations, molecular imaging techniques may play a promising role. Starting from the strengths and weaknesses of structural anatomical imaging, the present narrative review aims to highlight the promising role of molecular imaging in the assessment of non-neoplastic MSK diseases with a special focus on its role to monitor treatment response.


Asunto(s)
Radiología , Tomografía Computarizada por Rayos X , Humanos , Imagen Molecular , Radiografía , Ultrasonografía
17.
Biomedicines ; 9(3)2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33808956

RESUMEN

We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [18F]-FDG PET, including a dedicated brain acquisition at our institution between May and December 2020 following their recovery after SARS-Cov2 infection. Fourteen of these patients presented isolated persistent hyposmia (smell diskettes olfaction test was used). A voxel-wise analysis (using Statistical Parametric Mapping software version 8 (SPM8)) was performed to identify brain regions of relative hypometabolism in patients with hyposmia with respect to controls. Structural connectivity of these regions was assessed (BCB toolkit). Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in patients with respect to controls. Structural connectivity maps highlighted the involvement of bilateral longitudinal fasciculi. This study provides evidence of cortical hypometabolism in patients with isolated persistent hyposmia after SARS-Cov2 infection. [18F]-FDG PET may play a role in the identification of long-term brain functional sequelae of COVID-19.

18.
Diagnostics (Basel) ; 11(2)2021 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-33546455

RESUMEN

2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (FDG PET/CT) has an established clinical value in the diagnosis and initial staging of multiple myeloma (MM). In the last ten years, a vast body of literature has shown that this tool can also be of high relevance for monitoring therapy responses, making it the recommended imaging approach in this field. Starting from the strengths and weaknesses of radiological imaging in MM, the present review aims to analyze FDG PET/CT's current clinical value focusing on therapy response assessment and objective interpretation criteria for therapy monitoring. Given the potential occurrence of patients with MM showing non-FDG-avid bone disease, new opportunities can be provided by non-FDG PET tracers. Accordingly, the potential role of non-FDG PET tracers in this setting has also been discussed.

19.
Alzheimers Dement ; 17(8): 1277-1286, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33528089

RESUMEN

INTRODUCTION: We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. METHODS: Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age). RESULTS: Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent). DISCUSSION: These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.


Asunto(s)
Enfermedad de Alzheimer , Escolaridad , Lóbulo Frontal/metabolismo , Giro del Cíngulo/metabolismo , Enfermedad por Cuerpos de Lewy/metabolismo , Factores de Edad , Anciano , Encéfalo/metabolismo , Europa (Continente) , Fluorodesoxiglucosa F18/metabolismo , Humanos , Procesamiento de Imagen Asistido por Computador/estadística & datos numéricos , Tomografía de Emisión de Positrones
20.
Curr Radiopharm ; 14(3): 220-227, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32484775

RESUMEN

Sarcoidosis is a systemic inflammatory disease of unknown etiology, pathologically characterized by non-caseating granulomas involving several organs and tissues. This pathological process can eventually affect the heart during his course leading to fibrosis associated with systolic dysfunction, conduction disturbance, and even sudden cardiac death. Due to this prognostic impact, diagnosis is crucial to optimize clinical management. The low sensitivity of endomyocardial biopsy and its invasive nature prevents its application as a first-line diagnostic approach. Thus, several efforts have been dedicated to the identification of advanced imaging tools for the diagnosis and monitoring of cardiac involvement in systemic sarcoidosis, including Positron Emission Tomography (PET). Starting from strengths and disadvantages of 18F-Fluorodeoxyglucose (18F-FDG) PET imaging, the present narrative review will summarize state of the art and future perspectives about radiotracers other than 18F-FDG of potential interest in the field of CS, including somatostatin receptor- ligands, proliferation markers and hypoxia displaying agents.


Asunto(s)
Cardiomiopatías/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacología , Sarcoidosis/diagnóstico por imagen , Cardiomiopatías/terapia , Humanos , Aumento de la Imagen/métodos , Sarcoidosis/terapia
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