Positron emission tomography (PET) combined with computed tomography (CT) is an established diagnostic modality that has become an essential imaging tool in oncological practice. However, thanks to ...its noninvasive nature and its capability to provide physiological information, the main applications of this technique have significantly expanded.(18)F-labelled fluorodeoxyglucose (FDG) is the most commonly used radiopharmaceutical for PET scanning and demonstrates metabolic activity in various tissues. Since activated inflammatory cells, like malignant cells, predominantly metabolise glucose as a source of energy and increase expression of glucose transporters when activated, FDG-PET/CT can be successfully used to detect and monitor a variety of lung diseases, such as infections and several inflammatory conditions.The added value of FDG-PET/CT as a molecular imaging technique relies on its capability to identify disease in very early stages, long before the appearance of structural changes detectable by conventional imaging. Furthermore, by detecting the active phase of infectious or inflammatory processes, disease progression and treatment efficacy can be monitored.This review will focus on the clinical use of FDG-PET/CT in nonmalignant pulmonary diseases.
Doxorubicin (DOX)-based chemotherapy for Hodgkin lymphoma (HL) yields excellent disease-free survival, but poses a substantial risk of subsequent left ventricular (LV) dysfunction and heart failure, ...typically with delayed onset. At the cellular level, this cardiotoxicity includes deranged cardiac glucose metabolism.
By reviewing the hospital records from January 2008 through December 2016, we selected HL patients meeting the following criteria: ≥ 18 year-old; first-line DOX-containing chemotherapy; no diabetes and apparent cardiovascular disease; 18-fluoro-deoxyglucose positron emission tomography (
FDG-PET) scans before treatment (PET
), after 2 cycles (PET
) and at the end of treatment (PET
); at least one echocardiography ≥ 6 months after chemotherapy completion (ECHO
). We then evaluated the changes in LV
FDG standardized uptake values (SUV) during the course of DOX therapy, and the relationship between LV-SUV and LV ejection fraction (LVEF), as calculated from the LV diameters in the echocardiography reports with the Teicholz formula.
Forty-three patients (35 ± 13 year-old, 58% males) were included in the study, with 26 (60%) also having a baseline echocardiography available (ECHO
). LV-SUV gradually increased from PET
(log-transformed mean 0.20 ± 0.27) to PET
(0.27 ± 0.35) to PET
(0.30 ± 0.41; P for trend < 0.001). ECHO
was performed 22 ± 17 months after DOX chemotherapy. Mean LVEF was normal (68.8 ± 10.3%) and only three subjects (7%) faced a drop below the upper normal limit of 53%. However, when patients were categorized by median LV-SUV, LVEF at ECHO
resulted significantly lower in those with LV-SUV above than below the median value at both PET
(65.5 ± 11.8% vs. 71.9 ± 7.8%, P = 0.04) and PET
(65.6 ± 12.2% vs. 72.2 ± 7.0%, P = 0.04). This was also the case when only patients with ECHO
and ECHO
were considered (LVEF at ECHO
64.7 ± 8.9% vs. 73.4 ± 7.6%, P = 0.01 and 64.6 ± 9.3% vs. 73.5 ± 7.0%, P = 0.01 for those with LV-SUV above vs. below the median at PET
and PET
, respectively). Furthermore, the difference between LVEF at ECHO
and ECHO
was inversely correlated with LV-SUV at PET
(P < 0.01, R
= - 0.30).
DOX-containing chemotherapy causes an increase in cardiac
FDG uptake, which is associated with a decline in LVEF. Future studies are warranted to understand the molecular basis and the potential clinical implications of this observation.
Emerging evidence suggests that metformin, a widely used anti-diabetic drug, may be useful in the prevention and treatment of different cancers. In the present study, we demonstrate that metformin ...directly inhibits the enzymatic function of hexokinase (HK) I and II in a cell line of triple-negative breast cancer (MDA-MB-231). The inhibition is selective for these isoforms, as documented by experiments with purified HK I and II as well as with cell lysates. Measurements of
18
F-fluoro-deoxyglycose uptake document that it is dose- and time-dependent and powerful enough to virtually abolish glucose consumption despite unchanged availability of membrane glucose transporters. The profound energetic imbalance activates phosphorylation and is subsequently followed by cell death. More importantly, the "in vivo" relevance of this effect is confirmed by studies of orthotopic xenografts of MDA-MB-231 cells in athymic (nu/nu) mice. Administration of high drug doses after tumor development caused an evident tumor necrosis in a time as short as 48 h. On the other hand, 1 mo metformin treatment markedly reduced cancer glucose consumption and growth. Taken together, our results strongly suggest that HK inhibition contributes to metformin therapeutic and preventive potential in breast cancer.
Using a computational approach to extract the spinal canal from whole-body PET/CT images, Marini et al. reveal increased glucose consumption in the spinal cord in prospectively recruited patients ...with amyotrophic lateral sclerosis. Simultaneous measurement of brain 18F-Fluorodeoxyglucose uptake reveals a divergent metabolic response in the two structures.
Abstract
We recently reported the potential of Hough transform in delineating spinal cord metabolism by 18F-fluorodeoxyglucose PET/CT scanning in amyotrophic lateral sclerosis. The present study aimed to verify the relationship between spinal cord and brain metabolism in 44 prospectively recruited patients affected by amyotrophic lateral sclerosis submitted to 18F-fluorodeoxyglucose brain and whole-body PET/CT. Patients were studied to highlight the presence of brain hypo- or hypermetabolism with respect to healthy controls, and multiple regression analysis was performed to evaluate the correlation between spinal cord and brain metabolism. Our results confirmed higher 18F-fluorodeoxyglucose uptake in both cervical and dorsal spinal cord in patients with amyotrophic lateral sclerosis with respect to controls. This finding was paralleled by the opposite pattern in the brain cortex that showed a generalized reduction in tracer uptake. This hypometabolism was particularly evident in wide regions of the frontal-dorsolateral cortex while it did not involve the midbrain. Bulbar and spinal disease onset was associated with similar degree of metabolic activation in the spinal cord. However, among spinal onset patients, upper limb presentation was associated with a more pronounced metabolic activation of cervical segment. Obtained data suggest a differential neuro-pathological state or temporal sequence in disease progression.
The favourable kinetics of
F-fluoro-2-deoxyglucose (FDG) permits to depict cancer glucose consumption by a single evaluation of late tracer uptake. This standard procedure relies on the slow ...radioactivity loss, usually attributed to the limited tumour expression of G6P-phosphatase (G6Pase). However, this classical interpretation intrinsically represents an approximation since, as in all tissues, cancer G6Pase activity is remarkable and is confined to the endoplasmic reticulum (ER), whose lumen must be reached by phosphorylated FDG to explain its hydrolysis and radioactivity release. The present study tested the impact of G6Pase sequestration on the mathematical description of FDG trafficking and handling in cultured cancer cells. Our data show that accounting for tracer access to the ER configures this compartment as the preferential site of FDG accumulation. This is confirmed by the reticular localization of fluorescent FDG analogues. Remarkably enough, reticular accumulation rate of FDG is dependent upon extracellular glucose availability, thus configuring the same ER as a significant determinant of cancer glucose metabolism.
Purpose
Our aim was to compare a widely distributed commercial tool with an older free software (i) one another, (ii) with a clinical motor score, (iii) versus reading by experts.
Procedures
We ...analyzed consecutive scans from one-hundred and fifty-one outpatients submitted to brain DAT SPECT for a suspected parkinsonism. Images were post-processed using a commercial (Datquant®) and a free (BasGanV2) software. Reading by expert was the gold standard. A subset of patients with pathological or borderline scan was evaluated with the clinical Unified Parkinson’s Disease Rating Scale, motor part (MDS-UPDRS-III).
Results
SBR, putamen-to-caudate (P/C) ratio, and both P and C asymmetries were highly correlated between the two software with Pearson’s ‘
r
’ correlation coefficients ranging from .706 to .887. Correlation coefficients with the MDS-UPDRS III score were higher with caudate than with putamen SBR values with both software, and in general higher with BasGanV2 than with Datquant®. Datquant® correspondence with expert reading was 84.1% (94.0% by additionally considering the P/C ratio as a further index). BasGanV2 correspondence with expert reading was 80.8% (86.1% by additionally considering the P/C ratio).
Conclusions
Both Datquant® and BasGanV2 work reasonably well and similarly one another in semi-quantification of DAT SPECT. Both tools have their own strength and pitfalls that must be known in detail by users in order to obtain the best help in visual reading and reporting of DAT SPECT.
Background
Brain PET imaging with different tracers is mainly clinically used in the field of neurodegenerative diseases and brain tumors. In recent years, the potential usefulness of PET has also ...gained attention in the field of MS. In fact, MS is a complex disease and several processes can be selected as a target for PET imaging. The use of PET with several different tracers has been mainly evaluated in the research setting to investigate disease pathophysiology (i.e. phenotypes, monitoring of progression) or to explore its use a surrogate end-point in clinical trials.
Results
We have reviewed PET imaging studies in MS in humans and animal models. Tracers have been grouped according to their pathophysiological targets (ie. tracers for myelin kinetic, neuroinflammation, and neurodegeneration). The emerging clinical indication for brain PET imaging in the differential diagnosis of suspected tumefactive demyelinated plaques as well as the clinical potential provided by PET images in view of the recent introduction of PET/MR technology are also addressed.
Conclusion
While several preclinical and fewer clinical studies have shown results, full-scale clinical development programs are needed to translate molecular imaging technologies into a clinical reality that could ideally fit into current precision medicine perspectives.
The present study aims to verify the relationship between glucose consumption and uptake of 18F-2-deoxy-glucose (FDG) in the skeletal muscle (SM) of experimental models of streptozotocin-induced ...diabetes mellitus (STZ-DM).
The study included 36 Balb/c mice. Two weeks after intraperitoneal administration of saline (control group, n = 18) or 150 mg streptozotocin (STZ-DM group, n = 18), the two cohorts were submitted to an oral glucose tolerance test and were further subdivided into three groups (n = 6 each): untreated and treated with metformin (MTF) at low or high doses (10 or 750 mg/kg daily, respectively). Two weeks thereafter, all mice were submitted to dynamic micro–positron emission tomography (PET) imaging after prolonged fasting. After sacrifice, enzymatic pathways and response to oxidative stress were evaluated in harvested SM.
On PET imaging, the FDG uptake rate in hindlimb SM was significantly lower in nondiabetic mice as compared with STZ-DM–untreated mice. MTF had no significant effect on SM FDG uptake in untreated mice; however, its high dose induced a significant decrease in STZ-DM animals. Upon conventional analysis, the SM standard uptake value was higher in STZ-DM mice, while MTF was virtually ineffective in either control or STZ-DM models. This metabolic reprogramming was not explained by any change in cytosolic glucose metabolism. By contrast, it closely agreed with the catalytic function of hexose-6P-dehydrogenase (H6PD; i.e., the trigger of a specific pentose phosphate pathway selectively located within the endoplasmic reticulum). In agreement with this role, the H6PD enzymatic response to both STZ-DM and MTF matched the activation of the NADPH-dependent antioxidant responses to the increased generation of reactive oxygen species caused by chronic hyperglycemia. Ex vivo analysis of tracer kinetics confirmed that the enhanced SM avidity for FDG occurred despite a significant reduction in glucose consumption, while it was associated with increased radioactivity transfer to the endoplasmic reticulum.
These data challenge the current dogma linking FDG uptake to the glycolytic rate. They instead introduce a new model considering a strict link between the uptake of this glucose analog, H6PD reticular activity, and oxidative damage in diabetes, at least under fasting condition.
•The accepted link between glucose consumption and uptake of hexose analogs such as FDG and 2DG is looser than expected.•FDG selectively tracks the activity of a pentose-phosphate shunt triggered by H6PD.•FDG uptake in the skeletal muscles tracks the hyperglycemia-related oxidative damage.•FDG uptake might represent an index of NADPH renewal indicating the ER-PPP response to oxidative stress.
2-deoxy-2-18Ffluoro-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.
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