Comparisons between glucose analogue 2-deoxy-2-(^(18)F)fluoro-D-glucose and ^(18)F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions

AIM: To compare 2-deoxy-2-(^(18)F)fluoro-D-glucose(^(18)FFDG) and ^(18)F-sodium(^(18)F-NaF) positron emission tomography/computed tomography(PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases.METHODS: A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent ^(18)F-FDG and ^(18)F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity(Se), specificity(Sp), overall accuracy, positive and negative predictive values, error rate, and Youden's index. Mc Nemar's χ~2 test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the coregistered CT(sclerotic, lytic, mixed, no-lesions) and the divergent site of disease(skull, spine, ribs, extremities, pelvis). The impact of adding ^(18)F-Na F PET/CT to the work-up of patients was also measured in terms of change in their management due to ^(18)F-Na F PET/CT findings. RESULTS: The two imaging methods of ^(18)F-FDG and ^(18)F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively(Mc Nemar's χ~2 = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis(Mc Nemar's χ~2 = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, ^(18)F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis(P < 0.002) and vertebral localizations(P < 0.002); ^(18)F-Na F PET/CT was more accurate in detecting sclerotic(P < 0.005) and rib lesions(P < 0.04). ^(18)F-Na F PET/CT led to a change of management in 3 of the 45 patients(6.6%) by revealing findings that were not detected at ^(18)F-FDG PET/CT. CONCLUSION: ^(18)F-FDG PET/CT is a reliable imaging tool in the detection of bone metastasis in most cases, with a diagnostic accuracy that is slightly, but significantly, superior to that of ^(18)F-Na F PET/CT in the general population of breast cancer patients. However, the extremely high sensitivity of ^(18)F-fluoride PET/CT can exploit its diagnostic potential in specific clinical settings(i.e., small CT-evident sclerotic lesions, high clinical suspicious of relapse, and negative ^(18)F-FDG PET and conventional imaging).

Amyloid positron emission tomography and cognitive reserve

Alzheimer's disease(AD) is characterized by a nonlinear progressive course and several aspects influence the relationship between cerebral amount of AD pathology and the clinical expression of the disease. Brain cognitive reserve(CR) refers to the hypothesized capacity of an adult brain to cope with brain damage in order to minimize symptomatology. CR phenomenon contributed to explain the disjunction between the degree of neurodegeneration and the clinical phenotype of AD. The possibility to track brain amyloidosis(Aβ) in vivo has huge relevance for AD diagnosis and new therapeutic approaches. The clinical repercussions of positron emission tomography(PET)-assessed Aβ load are certainly mediated by CR thus potentially hampering the prognostic meaning of amyloid PET in selected groups of patients. Similarly, amyloid PET and cerebrospinal fluid amyloidosis biomarkers have recently provided new evidence for CR. The present review discusses the concept of CR in the framework of available neuroimaging studies and specifically deals with the reciprocal influences between amyloid PET and CR in AD patients and with the potential consequent interventional strategies for AD.

Correlation between thoracic aorta 18F-natrium fluoride uptake and cardiovascular risk

AIM: To investigating the relationship between thoracic and cardiac 18F-Natrium-Fluoride(18F-Na F) uptake,as a marker of ongoing calcification and cardiovascular risk factors.METHODS: Seventy-eight patients(44 females,mean age 63,range 44-83) underwent whole body 18F-Na F positron emission tomography/computed tomography. Cardiovascular risk(CVR) was used to divide these patients in three categories: Low(LR),medium(MR) and high risk(HR). 18F-Na F uptake was measured by manually drawing volumes of interest on the ascendingaorta,on the aortic arch,on the descending aorta and on the myocardium; average standardized uptake value was normalized for blood-pool,to obtain target-tobackground ratio(TBR). Values from the three aortic segments were then averaged to obtain an index of the whole thoracic aorta.RESULTS: A significant difference in whole thoracic aorta TBR was detected between HR and LR(1.84 ± 0.76 vs 1.07 ± 0.3,P < 0.001),but also between MR and HR-LR(1.4 ± 0.4,P < 0.02 and P < 0.01,respectively). Significance of this TBR stratification strongly varied among thoracic aorta subsegments and the lowest P values were reached in the descending aorta(P < 0.01). Myocardial uptake provided an effective CVR classes stratification(P < 0.001).Correlation between TBR and CVR was appreciable when the whole thoracic aorta was considered(R = 0.67),but it peaked when correlating the descending thoracic segment(R = 0.75),in comparison with the aortic arch and the ascending segment(R = 0.55 and 0.53,respectively). CONCLUSION: Fluoride uptake within the thoracic aorta wall effectively depicts patients' risk class and correlates with cardiovascular risk. Descending aorta is the most effective in CVR determination.

Evaluation of response to immune checkpoint inhibitors: Is there a role for positron emission tomography?

Strategies targeting intracellular negative regulators such as immune checkpoint inhibitors(ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the radiological effect of immunotherapeutic agents has raised several more relevant and complex challenges for the determination of their imaging-based response at single patient level. Accordingly, it has been suggested that the conventional Response Evaluation Criteria in Solid Tumors assessment alone, based on dimensional evaluation provided by computed tomography(CT), tends to underestimate the benefit of ICPIs at least in a subset of patients, supporting the need of immunerelated response criteria. Different from CT, very few data are available for the evaluation of immunotherapy by means of 18F-fluoro-2-deoxy-D-glucose positron emission tomography(FDG-PET). Moreover, since the antineoplastic activity of ICPIs is highly related to the activation of T cells against cancer cells, FDG accumulation might cause false-positive findings. Yet, discrimination between benign and malignant processes represents a huge challenge for FDG-PET in this clinical setting. Consequently, it might be of high interest to test the complex and variegated response to ICPIs by means of PET and thus it is worthwhile to ask if a similar introduction of immune-related PET-based criteria could be proposed in the future. Finally, PET might offer a new insight into the biology and pathophysiology of ICPIs thanks to a growing number of non-invasive immunediagnostic approaches based on non-FDG tracers.

Metformin and cancer: Technical and clinical implications for FDG-PET imaging

Metformin is the most widely used hypoglycemic agent. Besides its conventional indications, increasing evidence demonstrate a potential efficacy of this biguanide as an anticancer drug. Possible mechanisms of actions seem to be independent from its hypoglycemic effect and seemto involve the interference with key pathways in cellular proliferation and glycolysis. To date, many clinical trials implying the use of metformin in cancer treatment are on-going. The increasing use of 18F-2-fluoro-2-deoxyd-glucose positron emission tomography(FDG-PET) in cancer evaluation raises a number of questions about the possible interference of the biguanide on FDG distribution. In particular, the interferences exerted by metformin on AMP-activated protein kinase pathway(the cellular energy sensor), on insulin levels and on Hexokinase could potentially have repercussion on glucose handling and thus on FDG distribution. A better comprehension of the impact of metformin on FDG uptake is needed in order to optimize the use of PET in this setting. This evaluation would be useful to ameliorate scans interpretation in diabetic patients under chronic metformin treatment and to critically interpret images in the context of clinical trials. Furthermore, collecting prospective data in this setting would help to verify whether FDG-PET could be a valid tool to appreciate the anticancer effect of this new therapeutic approach.