Prevalence, distribution and clinical significance of joints, muscles and bones in sarcoidosis: an 18F-FDG-PET/CT study.

OBJECTIVES: In Sarcoidosis joints-muscles-bones (JMBs) localizations are of the least common. 18F-FDG-PET/CT imaging revolutionized detection of JMBs involvement by adding metabolic activity information and allowing for a comprehensive, whole-body mapping of the disease. AIM AND METHODS: This study investigated prevalence, distribution, and clinical significance of JMBs sarcoidosis in 195 consecutive patients that underwent 18F-FDG PET/CT examination. RESULTS: Joint and bone involvement were encountered in 15% of patients with a mean of the maximum-standardized-uptake-value (SUVmax) of 6.1. Most common location was the axial skeleton. Hypercalciuria was significantly more frequent in patients with osseous involvement (p = 0.003). Muscle activity (SUVmax = 2.4) was encountered in 20% of the patients, most frequently in treatment-naïve (p = 0.02). The muscles of the lower extremities were affected the most. Muscle and bone localization coexist in 50% of the cases. JMBs disease was almost asymptomatic, not related to chronicity but to pulmonary, nodal, and systemic disease. Long-term follow-up and treatment response of affected patients confirmed sarcoidosis. CONCLUSION: 18F-FDG-PET/CT revealed JMBs localizations and coexistence with other organ sites supporting the concept that sarcoidosis is a systemic disease. By allowing an integrative interpretation of multi-organ involvement in the context of a pattern highly suggestive of sarcoidosis, it strongly keeps-off the diagnosis of malignancy.

Lymphoma Severity and Type Are Associated With Aortic FDG Uptake by 18F-FDG PET/CT Imaging.

BACKGROUND: There is evidence that metabolic disease burden in lymphoma influences patient outcome. However, the impact of disease severity on the cardiovascular system is unknown. OBJECTIVES: The aim of this study was to examine whether lymphoma is associated with arterial inflammation by investigating the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake. METHODS: Sixty-two chemotherapy-naïve patients with active Hodgkin's or non-Hodgkin's lymphoma were matched (2:1) to individual control groups of lymphoma patients previously treated and free of active disease. All groups underwent 18F-FDG position emission tomography-computed tomography imaging. Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis corresponding to standardized uptake values (SUVs) ≥41% or ≥2.5 of the maximum SUV within lymphoma regions, and aortic FDG uptake was quantified through the target-to-background ratio (TBR). Inflammatory and disease severity biomarkers were also measured. RESULTS: MTV and total lesion glycolysis measurements were significantly correlated with inflammatory and disease biomarkers. Aortic TBR was higher in patients with active non-Hodgkin's lymphoma compared with control subjects (median difference 0.51; 95% confidence interval [CI]: 0.28 to 0.78; p < 0.001). Similarly, patients with active Hodgkin's lymphoma had higher values of aortic TBR compared with control subjects (median difference 0.31; 95% CI: 0.15 to 0.49; p < 0.001). In addition, aortic TBR was modestly increased in patients with stage III to IV disease compared with those with stage I to II disease (median aortic TBR: 2.23 [interquartile range: 2.01 to 2.54] vs. 2.06 [interquartile range: 1.83 to 2.27; p = 0.050). In multivariable analysis, aortic FDG uptake and MTV≥2.5 values were independently associated (ß = 0.425; 95% CI: 0.189 to 0.662; p = 0.001; R2 = 0.208), as were aortic FDG uptake and MTV≥41% (ß = 0.407; 95% CI: 0.167 to 0.649, p = 0.001; R2 = 0.191). CONCLUSIONS: Aortic wall FDG uptake is related with disease severity indicative of a possible vascular effect of lymphoma. This work highlights a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences on the vasculature.

18F-FDG PET/CT in Pulmonary Sarcoidosis:Quantifying Inflammation by the TLG index.

Objectives: In sarcoidosis progressive pulmonary disease affects prognosis. Pulmonary disease activity estimated by classic means poorly predicts severity and progressiveness. 18F-fluoro-2-deoxyglucose-positron-emission-tomography computed-tomography (18F-FDG-PET/CT) estimates pulmonary activity by inflammatory-cells metabolism. We aimed to investigate pulmonary sarcoidosis by 18F-FDG-PET/CT and evaluate the role of total-lesion-glycolysis (TLG) value, as an index quantifying the whole burden of lung inflammation.Methods: This is a retrospective study of sequentially gathered data. From a Greek cohort of 195 sarcoidosis-patients, 87 were identified with lung increased 18F-FDG uptake and further studied.Results: Visualizing lung by 18F-FDG-PET/CT identified new imaging patterns and revealed activity in all Scadding stages. Ever-smokers presented significantly higher TLG and lower DLCO compared to never-smokers. However, TLG value did not correlate with functional indices and did not differ between symptomatic and non-symptomatic patients. Among treatment-naïve patients, TLG did not differ significantly in those requiring therapy compared to those remained off.Conclusion: 18F-FDG PET/CT improved imaging and detection of pulmonary involvement and through TLG value revealed the deleterious smoking effect. The fact that TLG neither detected patients with clinical symptoms and functional impairment nor identified those requiring treatment once again confirms that in pulmonary sarcoidosis the link between activity, severity and decision to treat still eludes us.

Emerging phenotypes of sarcoidosis based on 18F-FDG PET/CT: a hierarchical cluster analysis.

Objectives: In sarcoidosis, the definition of organ involvement with traditional means appears laborious and somewhat controversial, and phenotyping by the above overlapping. 18F-FDG PET/CT defines disease extent by activity more precisely, and may result in a better understanding of sarcoidosis disease behavior and phenotypes expression. We hypothesized that 18F-FDG PET/CT could add in the phenotyping of sarcoidosis patients by unveiling in detail sites of involvement even in clinically and physiologically silent disease.Methods: This study was designed to investigate the role of 18F-FDG PET/CT in phenotyping sarcoidosis using cluster analysis by adding this new means in the routine work-up of 195 sarcoidosis patients of a single academic center.Results: 18F-FDG PET/CT succeeded to identify despite the random distribution of the disease, an ordered stratification into 4 phenotypes: I) thoracic nodal hilar-mediastinal, II) thoracic nodal hilar-mediastinal and lungs, III) an extended thoracic and extra-thoracic only nodal phenotype including inguinal-abdominal-supraclavicular stations, and IV) all the above plus systemic organs and tissues such as muscles-bones-spleen and skin.Conclusion: Though further studies are necessary to confirm findings as patterns of disease behavior; the proposed phenotypes may prove useful in the design of future studies with homogeneous cohorts facilitating in sarcoidosis patients a personalized medicine approach.

More advantages in detecting bone and soft tissue metastases from prostate cancer using 18F-PSMA PET/CT.

Prostate cancer (PCa) is the most common solid cancer affecting men worldwide. Serum prostate-specific antigen (PSA) is at present the most commonly used biomarker for PCa screening, as well as a reliable marker of disease recurrence after initial treatment. Bone metastases (BM) are present in advanced stages of the disease. Imaging of BM is important not only for localization and characterization, but also to evaluate their size and number, as well as to follow-up the disease during and after therapy. Bone metastases formation is triggered by cancer initiating cells in the bone marrow and is facilitated by the release of several growth factors. Although BM from PCa are very heterogenic, the majority of them are described as "osteoblastic", while pure "osteolytic" metastases are very rare. The PSA levels, along with other parameters, may determine the risk of having BM. A classification report, which is currently in use, divides patients into three categories according to the risk of having BM: low risk (PSA<10ng/mL, clinical stage T1-T2a, Gleason Score ≤6), intermediate risk (PSA 10.1-20ng/mL, clinical stage T2b-T2c, Gleason Score=7) and high risk (PSA>20ng/mL, clinical stage T3a or higher, or Gleason Score ≥8). Even though PSA remains the only biomarker of this disease in clinical practice, it is not always analogue with the severity of the disease and should be evaluated along with the clinical and diagnostic imaging findings. Detection of BM is not always easy, as there may be unexpected sites and occult metastases. The clinical importance of revealing BM in patients with PCa is to determine the overall survival of the patients and their quality of life, as BM may lead to high morbidity and mortality. There are many options of treating BM, such as chemotherapy, immunotherapy, external beam radiotherapy, bone modifying agents and recently prostate-specific membrane antigen (PSMA) targeted therapies. Another potential therapy is radioguided surgery, in patients with occult and/or focally recurrent PCa. Such a single occult metastasis causing very high levels of PSA has been presented using technetium-99m (99m Tc) labeled PSMA imaging. Diagnosis and staging of PCa mostly relies on the morphology of imaging, using computerized tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography/CT (PET/CT) using fluorine-18-fluorodeoxyglucose (18 F-FDG). The radiopharmaceuticals used in Nuclear Medicine for BM in PCa are: a) those that target lesions, such as 99m Tc-phosphonates, 18 F-sodium fluoride (18 F-NaF) and b) those that target the cancer cells, such as 18 F or carbon-11 (11 C)-choline, 18 F-FDG and 18 F or gallium-68 (68 Ga)-PSMA. Bone scan with 99mTc-phosphonates is widely used for the evaluation of bone metabolism in patients with PCa. It is a low cost, widely available radiopharmaceutical having the advantage of a whole body evaluation. Planar and single photon emission tomography (SPET) may also be applied. The sensitivity of the whole body scan (WBS) ranges from 75%-95%, while the specificity is lower, ranging from 60%-75% due to false positive findings in benign conditions (arthritis, inflammation etc) who also have increased bone metabolism. Sensitivity and specificity however, perform better (96% and 94% respectively) when SPET and SPET/CT techniques are applied. Of course, bone marrow metastases cannot be detected in a WBS. The PSA marker is used to predict the pre-test probability of BM and in case of a bone scan several retrospective analyses showed that PSA levels <20ng/mL can exclude with high probability a positive WBS, with a high negative predictive value (almost 99%). The European Association of Urology (EAU) guidelines state that a bone scan can be omitted in patients with PSA levels <20ng/mL and with a Gleason Score ≤7. Imaging with 18 F-NaF PET/CT is characterized by high and rapid bone uptake, minimal serum protein binding and rapid blood clearance which lead to a fast and high target to background ratio with a short acquisition time (30 minutes). Sensitivity and specificity for the detection of BM in high risk PCa patients is almost 100%. The main advantages provided by 18 F-NaF PET/CT are the better imaging quality along with a whole body acquisition and the fusion technique. Fluorine-18-choline and 11 C-choline PET/CT came to practice lately, reflecting the cell membrane metabolism. Choline is an essential component of phospholipids and is trapped in the cells after a phosphorylation by a choline kinase. The sensitivity and specificity of 18 F-choline PET/CT for detecting BM in patients with PCa is reported to be 79% and 97% respectively. However, the performance of choline PET/CT seems to be dependent of the levels of the PSA, in cases of biochemical recurrence and reaches about 75%% in those PCa patients with PSA levels >3ng/mL, with a poor performance when the PSA level is low. Fluorine-18-FDG is the most commonly used radiotracer in PET/CT, however has a little value in staging and restaging of PCa. Because of its low sensitivity 18 F-FDG is trapped in cancer cells through the activation of the glycolytic pathways and in case of BM is an index of increased glucose metabolism in PCa cells rather than in bone lesion per se. Osteolytic lesions show more increased metabolic activity than the osteoblastic lesions and are better revealed with 18F-FDG. Therefore, 18 F-FDG PET/CT is suggested to be performed only in selected patients with PCa, those with most aggressive tumors and high Gleason score. Fluorine-18-PSMA PET/CT The need of a more sensitive and specific agent has been evident. Prostate specific monoclonal antibody (PSMA) is a folate hydrolase cell surface glycoprotein. It is mainly expressed in four tissues of the body, including prostate epithelium, the proximal tubules of the kidney, the jejunal brush border of the small intestine and ganglia of the nervous system. So consequently may in some cases be expressed in cancers other than PCa and also in benign processes. It is localized in the cytoplasm and the apical side of the prostate epithelium that lines prostatic ducts. In case of malignant transformation, PSMA is transferred from the cytoplasm to the luminal surface of the prostatic ducts and thus becomes membrane bound. It has a unique three-parts structure, an external portion, a transmembrane portion and an internal-cytoplasmatic portion. Prostate specific monoclonal antibody is also upregulated and thus overexpressed in most PCa, but weakly expressed in normal prostatic tissue. Imaging by PSMA PET/CT has been shown to detect sites of disease recurrence at lower PSA levels than conventional imaging. The PSMA overexpression is even present when the cell becomes castrate-resistant and that is the reason why it is the most favorable target for PET imaging. Prostate cancer expresses 100 to 1000 times more PSMA than normal tissue and is increasing even more in higher grade tumors as well as in increased castrate resistance. Therefore, PSMA represents an excellent target for both diagnostic imaging and endoradiotherapy of PCa. For diagnostic purposes PSMA ligands, mainly small-molecule inhibitors, are most commonly labeled either with 68 Ga or 18 F. The 18 F-PSMA-1007 (((3S,10S,14S)-1-(4-(((S)-4-carboxy-2-((S)-4-carboxy-2-(6-18 F-fluoronicotinamido) butanamido) methyl phenyl)-3- (naphthalen-2-ylmethyl)-1,4,12-trioxo-2,5,11,13-tetraazahexadecane- 10,14,16-tricarboxylic acid)) seems to be more favorable among other 18 F-PSMA ligands candidate compounds because it demonstrates high labeling yields, better tumor uptake and non-urinary background clearance. On the contrary, 68 Ga-PSMA is rapidly excreted via the urinary tract resulting in intense accumulation in the bladder, thus, obscuring the prostate. Compared to 68 Ga, 18 F has many advantages such as it is produced in larger amounts, it has a longer half life and a higher physical spatial resolution. The short half-life of 68 Ga relative to 18 F (68 vs. 110 min) makes 68 Ga-PSMA inconvenient for longer transport, so that it is almost mandatory to use local gallium generators, which have a higher cost and lower yields at the end of their first half-life. Each generator provides only one or two elutions per day and it requires separate syntheses at different times of the day in a local radiopharmacy. Furthermore, the resolution of 68 Ga-labeled tracers is physically limited because of positron range effects. In contrast, 18 F labels avoid these intrinsic difficulties and can be produced at high yields in central cyclotrons. Fluorine-18-PSMA-1007 has been recently used by us in the Nuclear Medicine Department of "Evangelismos" general hospital of Athens and our experience so far showed favorable results, with high image resolution acquisitions and lesions which showed PSMA avidity. Fluorine-18-PSMA-1007 PET/CT imaging was carried out with a dual phase protocol, consisting of two separate scans. One (early scan) at 60min post injection starting from the diaphragm to the middle of the thighs and the late scan at 180min from the dome of the skull to the knee joints. Patients were asked to urine before the examination. Images were acquired with a scan time of 3min per bed position on a General Electric PET/CT system and the image reconstruction was performed by the standard software method provided by the manufacturer. A low dose CT scan, without a contrast agent, was performed before the PET scan in order to be used for the attenuation correction. Administered activities were calculated based on the department's protocols with a suggested injected activity of 4MBq/kg. Any areas of focally increased radiotracer uptake, at both the early and late PET scans, were considered as abnormal, despite the presence or absence of morphological changes of the CT scan. The normal distribution of the radiotracer was taken underconsideration, which includes mainly the liver and the gallbladder, as it has hepatobiliary clearance rather than renal, the spleen, the pancreas, the submandibular, sublingual, lacrimal and parotid glands, the kidneys, the urinary bladder and the small intestine. The maximum standardized uptake value (SUVmax) was calculated for each lesion. A typical case of a 78 years man with PCa having PSA 7,3ng/mL and also having Paget's disease was tested by the above procedure for initial staging. The 18 F-PSMA-1007 PET/CT imaging revealed diffusely increased radiotracer uptake in the bones of the pelvis with a SUVmax 9. The CT imaging of the pelvis was consistent with Paget's disease, with diffuse mixed osteosclerotic and osteolytic lesions, accompanied with bone expansion. The primary PCa was also revealed with focally increased radiotracer uptake in the left prostatic lobe with a SUVmax 19, as well as a second small focus of pathologically increased PSMA uptake in the right prostatic lobe with a SUVmax 23. Another patient 79 years old, with PCa was studied with 18 F-choline PET/CT which showed diffuse bone metastasis in the pelvis. He had PSA level, 412ng/mL. The 18 F-PSMA-1007 PET/CT imaging showed multiple foci of increased radiotracer uptake throughout the whole skeleton, including the skull, both humerus and femoral bones with indicative SUVmax 26. Computed tomography showed rather similar BM. There were also lymph nodes metastases at the left internal mammary chain as well as the left inguinal areas, with a SUVmax 25. The first case indicated that 18 F-PSMA PET/CT could easily differentiate PCa BM from Paget's disease, however benign conditions such as Paget's disease may also show PSMA uptake and the second case that 18 F-PSMA PET/CT scan was more sensitive than the 18 F-choline PET/CT scan, with high quality images. According to other authors the SUVmax value of BM in PCa was 16.57±23.59 using the 18 F-PSMA PET/CT scan. This imaging modality in accordance to other authors is better than 68 Ga-labelled PSMA-ligands and can better differentiate BM from healing fractures. Very recently a novel PET radiopharmaceutical has been approved both in USA and Europe: 18 F-fluciclovine (trans-1-amino-3-[18 F] fluoro-cyclobutane carboxylic acid). Fluorine-18-fluciclovine is a synthetic amino acid that is transported by multiple sodium-dependent and sodium-independent channels found to be upregulated in PCa cells. The main indication of use includes the detection and localization of PCa recurrence in patients with a rising PSA following prior therapy. The main advantages of 18 F-fluciclovine are the low urinary excretion, which allows for better evaluation of prostate bed and the low uptake in inflammatory cells (e.g. macrophages). There are no studies in the literature comparing 18 F-PSMA to 18 F-fluciclovine, however two studies comparing 18 F-fluciclovine to 68 Ga-PSMA, showed better performance for 68 Ga-PSMA in PCa patients with biochemical recurrence. So, 18 F-PSMA-1007 PET/CT imaging seems to be very promising in staging and restaging patients with PCa, especially when biochemical relapse is under consideration. Although it seems to perform better than other imaging modalities like bone scan, 18 F-FDG PET/CT or 18 F-choline PET/CT, its high cost and low availability must be considered. Further large studies need to be conducted in order to evaluate the accuracy and the predictive values of this method, emphasizing on bone metastases.

Adjustment of vascular 2-deoxy-2-[18F]fluoro-D-glucose uptake values over time through a modeling approach.

To develop and test a model predicting 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) standardized uptake value (SUV) changes over time in the aorta and the superior vena cava (SVC). Maximum aortic SUV and mean SVC SUV were determined at two time points (T1 and T2) in the ascending (ASC), descending (DSC), abdominal (ABD) aorta, aortic arch (ARC) and SVC of patients who have undergone [18F]FDG PET/CT for clinical purposes. For SUV prediction at T2, linear and non-linear models of SUV difference for a given time change were developed in a derivation group. The results were tested in an independent validation group, whilst model reproducibility was tested in patients of the validation group who have undergone a second clinically indicated scan. Applying the linear model in the derivation group, there were no statistically significant differences in measurements obtained in the examined segments: mean differences ranged from 0 ± 0.10 in SVC to 0.01 ± 0.13 in ARC between measured and predicted SUV. In contrast, in the non-linear model, there were statistically significant differences in measurements, except in ARC, with mean differences ranging from 0.04 ± 0.14 in ARC to 0.28 ± 0.13 in ABD. In the validation group using the linear model, there were no statistically significant differences, with mean differences ranging from - 0.01 ± 0.08 in ASC to - 0.03 ± 0.11 in ABD. Regarding reproducibility, mean differences were no statistically significant, ranging from 0.004 ± 0.06 in ASC to - 0.02 ± 0.16 in ABD. We have developed a linear model allowing accurate and reproducible prediction of SUV changes over time in the aorta and SVC.

Vascular inflammation and metabolic activity in hematopoietic organs and liver in familial combined hyperlipidemia and heterozygous familial hypercholesterolemia.

BACKGROUND: Familial dyslipidemias of either heterozygous (heFH) or combined (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk. OBJECTIVE: The aim of this study was to investigate in statin-naïve adult patients with familial dyslipidemias whether inflammatory activation and liver, spleen and bone marrow metabolic activity differ compared with normolipidemic subjects and between dyslipidemic groups. METHODS: Fourteen patients with FCH, 14 with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high-sensitivity C-reactive protein, and fibrinogen levels were measured, followed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was quantified as tissue-to-background ratio (TBR). RESULTS: Patients with heFH had significantly higher low-density lipoprotein levels compared with those with FCH and controls (P < .001). However, aortic TBRs were higher in FCH compared with heFH patients and controls (P = .02 and P < .001, respectively). FCH patients exhibited higher FDG uptake in the spleen compared with controls (P = .05). In addition, FCH exhibited higher bone marrow FDG uptake compared with heFH patients and controls (P = .03 and P = .02, respectively). FCH had higher liver uptake compared with heFH patients and controls (P < .001 for both). Significant correlations were observed between inflammatory biomarkers and imaging indices as well as between aortic TBR and FDG uptake of hematopoietic organs and liver. CONCLUSIONS: Systemic, as well as vascular inflammation and spleen, bone marrow, and hepatic metabolic activity are increased in patients with FCH despite lower levels of low-density lipoprotein.

Inflamed human carotid plaques evaluated by PET/CT exhibit increased temperature: insights from an in vivo study.

AIMS: To explore the relationship between temperature measurements derived by microwave radiometry (MWR) and carotid flurodeoxyglucose (FDG) uptake and assess their association with histological and immunohistochemistry findings in patients with high-grade carotid stenosis. METHODS AND RESULTS: In 21 patients undergoing carotid endarterectomy, carotid inflammation was evaluated by both FDG positron emission/computed tomography (FDG-PET/CT) imaging and MWR measurements. Carotid inflammation was assessed by PET/CT as target-to-background ratio (TBR) by obtaining measurements in consecutive axial slices 2 cm below to 2 cm above the carotid bifurcation. Temperature difference (ΔT) by MWR was assigned as the maximum-minimum temperature measurements over the corresponding carotid segments. The extent of lipid core, calcification as well as CD68 and CD31 levels were also assessed. There was a significant correlation between ΔT values and FDG uptake (R = 0.40, P = 0.01), but no correlation between the degree of angiographic stenosis and ΔT values (R = -0.02, P = 0.91) or PET/CT measurements (R = -0.28, P = 0.86). Patients with plaques containing high lipid core extension or low calcification exhibited higher ΔT (P = 0.001 and P < 0.001, respectively) and FDG uptake values (P = 0.02 and P = 0.02, respectively). Patients with plaques containing increased CD68 expression exhibited higher ΔT and FDG uptake measurements. CONCLUSION: Carotid plaque inflammation was evaluated by temperature measurements, which were correlated with FDG-PET/CT indices, confirmed by histopathology and immunohistochemistry findings. Structural changes did not predict inflammatory process. The implications of these findings in risk stratification and management of patients with carotid atherosclerosis and the precise algorithm for potential clinical utilization of MWR and PET/CT remain to be determined.

Central nervous system disorders affecting the heart-insights from radionuclide imaging.

There is a growing research activity focusing on the brain heart cross-talk. A great variety of brain disorders affect the heart and recent developments in neurosciences have revealed the particular role of specific neuroanatomic sites on heart rhythm and rate, myocardial function and vascular tone. Cardiac radionuclide imaging plays a pivotal role in this setting, since not only helps elucidating underlying pathobiological mechanisms but in addition, it promises exciting possibilities for early identification of patients at risk of developing cardiovascular manifestations of certain neurological diseases.

[The role of positron emission tomography in in lymphoma diagnosis and treatment].

UNLABELLED: Objective and description of the review: To describe the role of PET and PET/CT as a better technique than gallium-67-citric or radiology in diagnosing histotypes of lymphoma and in following treatment. Lugano system is indicated for the specific diagnosis of histotypes, except in cases who do not take-up the radioactive agents such as the external lymphadenic border line B-lymphoma, lymphoma from small B- cells and spongoid mycosis. Treatment results are estimated by the PET/CT scans especially in Hodgkin's lymphoma. Favourable treatment in all lymphomas is estimated by the higher uptake of the radiopharmaceutical. In resistant cases, negative PET/CT scan suggests possible bone-marrow cells transplantation. CONCLUSION: The PET/CT scan can identify the stages and evaluate treatment results, of lymphomas.

(18)F-fluorodeoxyglucose positron emission tomography/computed tomography in infected polycystic kidney disease.

A positron emission tomography/computed tomography (PET/CT) study using (18)F-fluorodeoxyglucose ((18)F-FDG) was performed in a 54-year-old female with polycystic kidney disease, fever, and abdominal discomfort. Cyst's infection was suspected, but CT and U/S findings were not specific to accurately depict pyocysts and guide surgical treatment. In PET/CT, both kidneys are enlarged with multiple cysts and little remaining parenchyma. There is intense focal or ring-shaped FDG uptake in cysts in the upper and lower poles of the left kidney indicative of active infection. There is also increased FDG uptake in para-aortic lymph nodes bilaterally. Hepatic and right renal cysts do not present increased FDG uptake. As this case illustrates, FDG PET/CT can be helpful for the precise localization of cyst infections in patients with polycystic kidney disease considered for surgical treatment.

Lack of association between KRAS mutations and 18F-FDG PET/CT in Caucasian metastatic colorectal cancer patients.

BACKGROUND: Although Kirsten rat sarcoma (KRAS) gene mutational testing is essential for the optimal design of therapeutic strategies for colorectal cancer, it is not always feasible or reliable. In this retrospective study, we examined whether (18)F-Fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) scans can serve as a surrogate examination for KRAS mutational testing. PATIENTS AND METHODS: KRAS codon 12 and 13 mutational status was tested in 44 colorectal primary tumors and was compared with the (18)F-FDG PET/CT maximum standardized uptake value (SUVmax) values of the respective metastatic lesions. Glucose transporter-1 (GLUT1) mRNA levels were also measured in colorectal primary tumors. RESULTS: No statistically significant correlation between (18)F-FDG PET/CT SUVmax values and KRAS mutation status was found (parametric t-test: p=0.4753; non-parametric Kruskal-Wallis test: p=0.51). This result cannot be attributed to the effect of differing GLUT1 mRNA levels, as shown by multivariate analysis. CONCLUSION: Our study failed to promote (18)F-FDG PET/CT uptake as a surrogate examination for KRAS mutation testing.

Recurrent thyroid cancer diagnosis: ROC study of the effect of a high-resolution head and neck 18F-FDG PET/CT scan.

RATIONALE AND OBJECTIVES: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has demonstrated significant value in the evaluation of patients with indication of recurrent thyroid cancer with negative conventional workup. The hypothesis of this study was that the addition of a dedicated, high-resolution head and neck scan (HNS) to the standard whole-body scan (WBS) improves the accuracy of the detection and diagnosis of recurrent thyroid cancer. MATERIALS AND METHODS: Forty-three consecutive patients suspected for recurrent thyroid cancer, as indicated by increased tumor markers, prospectively underwent a WBS and a HNS with (18)F-FDG PET/CT. The patients were followed up to establish ground truth. A receiver operator characteristic (ROC) study with two observers was conducted to evaluate the impact of the additional HNS on the detection and diagnosis of recurrent thyroid cancer. Indices of performance included the area under the ROC curve (AUC), the number of detected abnormal foci, and the size of the detected foci without and with the HNS images. RESULTS: ROC results showed that the addition of the HNS to the standard WBS increased the average AUC index of performance from 0.69 to 0.96, a statistically significant difference with a confidence interval (CI) of -0.33 to -0.19. Diagnosis was also improved with the average AUC increasing from 0.79 to 0.87 but differences were not statistically significant (CI, -0.19 to 0.04). Interreader agreement was "good" in the detection task and "excellent" in the diagnostic task. The addition of the HNS increased the number of detected foci in the positive patients by an average of 37%, whereas false-positive detections in the negative patients increased by an average of 10%. Reported average maximum lesion size also increased with the HNS addition by an average of 11%. CONCLUSIONS: The addition of a high-resolution HNS to the standard whole-body PET/CT imaging improves readers' performance in the detection and diagnosis of recurrent thyroid cancer and could greatly benefit patient care.

Assessment of myocardial perfusion and viability by positron emission tomography.

An important evolution has taken place recently in the field of cardiovascular Positron Emission Tomography (PET) imaging. Being originally a highly versatile research tool that has contributed significantly to advance our understanding of cardiovascular physiology and pathophysiology, PET has gradually been incorporated into the clinical cardiac imaging portfolio contributing to diagnosis and management of patients investigated for coronary artery disease (CAD). PET myocardial perfusion imaging (MPI) has an average sensitivity and specificity around 90% for the detection of angiographically significant CAD and it is also a very accurate technique for prognostication of patients with suspected or known CAD. In clinical practice, Rubidium-82 ((82)Rb) is the most widely used radiopharmaceutical for MPI that affords also accurate and reproducible quantification in absolute terms (ml/min/g) comparable to that obtained by cyclotron produced tracers such as Nitrogen-13 ammonia ((13)N-ammonia) and Oxygen-15 labeled water ((15)O-water). Quantification increases sensitivity for detection of multivessel CAD and it may also be helpful for detection of early stages of atherosclerosis or microvascular dysfunction. PET imaging combining perfusion with myocardial metabolism using (18)F-Fluorodeoxyglucose ((18)F FDG), a glucose analog, is an accurate standard for assessment of myocardial hibernation and risk stratification of patients with left ventricular dysfunction of ischemic etiology. It is helpful for guiding management decisions regarding revascularization or medical treatment and predicting improvement of symptoms, exercise capacity and quality of life post-revascularization. The strengths of PET can be increased further with the introduction of hybrid scanners, which combine PET with computed tomography (PET/CT) or with magnetic resonance imaging (PET/MRI) offering integrated morphological, biological and physiological information and hence, comprehensive evaluation of the consequences of atherosclerosis in the coronary arteries and the myocardium.

Impact of 18F-FDG PET/CT on therapeutic decisions in patients with colorectal cancer and liver metastases.

OBJECTIVES: Surgical resection and radio-frequency ablation (RFA) are standard therapeutic procedures for colorectal metastases confined to the liver. The presence of extrahepatic disease has a significant effect on the management of these patients. The goal of this study is to assess the value of positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) in the decision making whether to perform RFA or surgical resection of liver metastases in patients with metastatic colorectal cancer. MATERIAL AND METHODS: Thirty-five consecutive patients (23 men, 12 women; age range: 46-78 years) with colorectal carcinoma and liver metastases were prospectively enrolled. Nineteen of them were considered candidates for surgical resection and 16 for RFA. All underwent 18F-FDG PET/CT, helical computed tomography of the chest and abdomen and, some of them, magnetic resonance imaging of the abdomen. The 18F-FDG PET/CT studies were performed within 4 weeks from conventional imaging, and additional findings were later confirmed or not, either by histology or follow up. RESULTS: In the surgical candidate group, 18F-FDG PET/CT detected extrahepatic disease, missed by conventional imaging, in 9/19 patients (47.3%). These findings directly altered the management in 7 patients (36.8%). In the group of RFA candidates, 18F-FDG PET/CT detected additional extrahepatic disease in 4/16 patients (25%) and directly altered management in all of them. Overall, in 11/35 patients (31.4%), 18F-FDG PET/CT detected extrahepatic metastatic disease. CONCLUSION: In patients with colorectal cancer and liver metastases, 18F-FDG PET/CT provides relevant additional information that has significant impact on management.

Can pain influence the severity of findings of an (18)F-FDG PET/CT scan in loosening hip arthroplasty?

Pain is a common symptom after loosening and/or after infection of arthroplasty. The aim of the present case report is to indicate that fluorine-18-fluorodeoxy-glucose positron emission tomography/computerized tomography((18)F-FDG PET/CT) scan can be used for the evaluation of pain at the site of arthroplasty with a semi quantitative measurement. An 84 years old male patient, with a history of papillary thyroid cancer was referred to our Nuclear Medicine Department for an (18)F-FDG PET/CT scan for evaluation of his metastatic disease. He reported right hip prosthesis thirty years ago and now suffered from significant pain in the right hip joint which on a scale from 1 to 10 could be rated as grade 8. White blood cell count, sedimentation rate and C-reactive protein were within normal limits. Four years ago he also had severe pain on the right leg that could be rated as grade 8, and underwent an (18)F-FDG PET/CT scan that showed a maximum standardized uptake value (SUV(max)) of 9.8. A year later, at a follow up (18)F-FDG PET/CT scan and under a similar severe pain, SUV(max) was 10. The patient had a hip prosthesis in the left leg 3 years ago, for which he reported pain that could be rated as grade 3 and the SUV(max) was then 3.7. The degree of (18)F-FDG uptake is related to cellular metabolic rate and to the number of glucose transporters. In inflammation, the activated inflammatory cells demonstrate increased expression of glucose transporters and the affinity of glucose transporters for deoxyglucose is increased by various cytokines and growth factors. Furthermore, when the mononuclear cells and the granulocytes are activated by certain infectious humoral stimuli, they use large amounts of glucose by the hexose monophosphate shunt and the rate of oxygen uptake is intensely increased, during the so called "respiratory burst". In the present case, it was interesting to note that the degree of (18)F-FDG uptake at the sites of loosening hip arthroplasty was related to the severity of pain. Signs of infection or inflammation although not obvious in our case, could not be excluded because sensitivity, specificity and accuracy of PET for detecting infection associated with hip prostheses has been reported to be, 90%, 89.3% and 89.5%, respectively and sensitivity and specificity for detecting periprosthetic inflammation 100% and 45.5%,respectively. In another study using as a criterion for periprosthetic infection the increased (18)F-FDG activity at the bone-prosthesis interface of the femoral component, sensitivity, specificity, positive and negative predictive values for the (18)F-FDG PET study where 85%, 93%, 80% and 95%, respectively. Inflammation, often intense, may be present in aseptic loosening and characterized by increased periprosthetic (18)F-FDG uptake. In conclusion, in our case the degree of (18)F-FDG uptake in a loosening hip arthroplasty was related to the severity of pain although inflammation or infection could also play some role. Further studies are required to prove this suggestion.