Role of F-18 FDG PET-CT in neuropsychiatric systemic lupus erythematosus.

BACKGROUND: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a major contributor to morbidity and mortality in systemic lupus erythematosus (SLE) patients. To date no single clinical, laboratory or imaging test has proven accurate for NPSLE diagnosis which is a testament to the intricate and multifactorial pathophysiological mechanisms suspected to exist. Functional imaging with FDG PET-CT has shown promise in NPSLE diagnosis, detecting abnormalities prior to changes evident on anatomical imaging. Research indicates that NPSLE may be more aggressive in people of African descent with higher mortality rates, making rapid and correct diagnosis even more important in the African context. METHODS: In this narrative review, we provide a thorough appraisal of the current literature on the role of FDG PET-CT in NPSLE. Large, well-known databases were searched using appropriate search terms. Manual searches of references of retrieved literature were also included. FINDINGS: A total of 73 article abstracts were assessed, yielding 26 papers that were directly relevant to the topic of FDG PET-CT in NPSLE. Results suggest that FDG PET-CT is a sensitive imaging test for NPSLE diagnosis and may play a role in assessing treatment response. It is complementary to routine anatomical imaging, particularly in diffuse manifestations of the disease. Newer quantitative analyses are commonly used for interpretation and can detect even subtle abnormalities, missed on visual inspection. Findings of group-wise analyses of FDG PET-CT scans in NPSLE patients are important in furthering our understanding of the complicated pathophysiological mechanisms involved. Limitations of FDG PET-CT include its lack of specificity, high cost and poor access. CONCLUSION: FDG PET-CT is a sensitive test for NPSLE diagnosis but is hampered by lack of specificity. It is a valuable tool for clinicians managing SLE patients, particularly when anatomical imaging is negative. Its exact application will depend on the local context and clinical scenario.

Estimated glomerular filtration rate in children: adapting existing equations for a specific population.

BACKGROUND: Creatinine-based glomerular filtration rate (GFR)-estimating equations frequently do not perform well in populations that differ from the development populations in terms of mean GFR, age, pathology, ethnicity, and diet. After first evaluating the performance of existing equations, the aim of this study was to demonstrate the utility of an in-house modification of the equations to better fit a specific population. METHODS: Estimated GFR using 8 creatinine-based equations was first compared to 2-sample 51Cr-ethylenediaminetetra-acetic acid plasma clearance in non-cancer and cancer groups independently. The groups were then divided into development and validation sets. Using the development set data, the Microsoft® Excel SOLVER add-in was used to modify the parameters of 7 equations to better fit the data. Using the validation set data, the performance of the original and modified equations was compared. RESULTS: Two hundred fifty-six GFR measurements were performed in 160 children. GFR was overestimated in both groups (non-cancer 4.3-22.6 ml/min/1.73 m2, cancer 17.2-46.6 ml/min/1.73 m2). The root mean square error (RMSE) was 19.1-21.8 ml/min/1.73 m2 (non-cancer) and 18.6-20.8 ml/min/1.73 m2 (cancer). The P30 values were 49.1-73.0% (non-cancer) and 19.6-66.0% (cancer). Modifying the parameters of seven equations resulted in significant improvements in the P30 values in the non-cancer (65.0-85.0%) and cancer (79.6-87.8%) groups. CONCLUSIONS: Modifying the parameters of pediatric GFR estimating-equations using a simple Excel-based tool significantly improved their accuracy in both non-cancer and cancer populations. Graphical abstract.

Simple Anatomical Calculations Possibly As Accurate As Three-Dimensional Lobar Quantification with SPECT-CT in Predicting Lung Function after Pulmonary Resection.

The estimation of predicted postoperative (PPO) lung function is important in lung resection candidates. We utilized simple anatomical calculations and single-photon emission computed tomography combined with computed tomography (SPECT-CT) to calculate PPO in 24 consecutive patients with impaired pulmonary function who underwent lung resection. PPO values calculated by anatomical calculations and three-dimensional lobar SPECT-CT quantification both correlated well with the postoperative forced expiratory volume in 1 s, with r = 0.825, p < 0.001 and r = 0.796, p < 0.001, respectively. Both techniques fared well at predicting postoperative lung function, but our observations unexpectedly suggested that simple anatomical calculations might be equivalent to three-dimensional SPECT-CT lobar quantification.

Resting regional brain metabolism in social anxiety disorder and the effect of moclobemide therapy.

While there is mounting evidence of abnormal reactivity of several brain regions in social anxiety disorder, and disrupted functional connectivity between these regions at rest, relatively little is known regarding resting regional neural activity in these structures, or how such activity is affected by pharmacotherapy. Using 2-deoxy-2-(F-18)fluoro-D-glucose positron emission tomography, we compared resting regional brain metabolism between SAD and healthy control groups; and in SAD participants before and after moclobemide therapy. Voxel-based analyses were confined to a predefined search volume. A second, exploratory whole-brain analysis was conducted using a more liberal statistical threshold. Fifteen SAD participants and fifteen matched controls were included in the group comparison. A subgroup of SAD participants (n = 11) was included in the therapy effect comparison. No significant clusters were identified in the primary analysis. In the exploratory analysis, the SAD group exhibited increased metabolism in left fusiform gyrus and right temporal pole. After therapy, SAD participants exhibited reductions in regional metabolism in a medial dorsal prefrontal region and increases in right caudate, right insula and left postcentral gyrus. This study adds to the limited existing work on resting regional brain activity in SAD and the effects of therapy. The negative results of our primary analysis suggest that resting regional activity differences in the disorder, and moclobemide effects on regional metabolism, if present, are small. While the outcomes of our secondary analysis should be interpreted with caution, they may contribute to formulating future hypotheses or in pooled analyses.

Resting-state fMRI and social cognition: An opportunity to connect.

Many psychiatric disorders are characterized by altered social cognition. The importance of social cognition has previously been recognized by the National Institute of Mental Health Research Domain Criteria project, in which it features as a core domain. Social task-based functional magnetic resonance imaging (fMRI) currently offers the most direct insight into how the brain processes social information; however, resting-state fMRI may be just as important in understanding the biology and network nature of social processing. Resting-state fMRI allows researchers to investigate the functional relationships between brain regions in a neutral state: so-called resting functional connectivity (RFC). There is evidence that RFC is predictive of how the brain processes information during social tasks. This is important because it shifts the focus from possibly context-dependent aberrations to context-independent aberrations in functional network architecture. Rather than being analysed in isolation, the study of resting-state brain networks shows promise in linking results of task-based fMRI results, structural connectivity, molecular imaging findings, and performance measures of social cognition-which may prove crucial in furthering our understanding of the social brain.

Alcohol-induced psychotic disorder: brain perfusion and psychopathology--before and after anti-psychotic treatment.

Alcohol-induced psychotic disorder (AIPD) also known as alcohol hallucinosis is a rare complication of alcohol abuse. The pathogenesis and treatment of AIPD are still unclear. Few prospective treatment studies are available but case reports generally suggest that anti-psychotic treatment is effective. Brain imaging changes in relation to treatment response have also not been studied except for case reports. The aim of this study was to investigate the effect of anti-psychotic treatment on psychopathology and regional cerebral blood flow (rCBF) in patients with AIPD before and after 6 weeks of treatment. Nineteen patients with AIPD were assessed by the Positive and Negative Syndrome Scale (PANSS) and single photon emission computed tomography (SPECT) before and after 6-weeks of open-label treatment with a fixed dose of haloperidol (5 mg/day). Highly significant improvements were noted on the positive, general and total scores of the PANSS. Post-treatment increased rCBF to the left caudate and left frontal lobe was noted. Changes in frontal, temporal, parietal, occipital, thalamic and cerebellar rCBF showed significant negative correlations with the degree of symptom improvement, suggesting dysfunction of these areas in AIPD. Psychopathological and rCBF findings suggest reversible generalised cerebral dysfunction in AIPD.

PET-CT in brain disorders: The South African context.

Positron emission tomography combined with X-ray computed tomography (PET-CT) has an established role in the management of brain disorders, but may be underutilised in South Africa. Possible barriers to access include the limited number of PET-CT facilities and the lack of contemporary guidelines for the use of brain PET-CT in South Africa. The current review aims to highlight the evidence-based usage of brain Positron emission tomography (PET) in dementia, movement disorders, brain tumours, epilepsy, neuropsychiatric lupus, immune-mediated encephalitides, and brain infections. While being areas of research, there is currently no clinical role for the use of PET-CT in traumatic brain injury or in psychiatric or neurodevelopmental disorders. Strategies to expand the appropriate use of PET-CT in brain disorders are discussed in this article.

Repeatability of glomerular filtration rate studies performed using 99mTc-DTPA in a population including cancer patients.

OBJECTIVE: Glomerular filtration rate (GFR) measurement remains an integral investigation in clinical practice and is particularly important in the prediction and follow-up of renal side-effects of nephrotoxic chemotherapy in cancer patients. Knowing the coefficient of variation (CV) of a test is vital for the correct interpretation of serial studies. Recent difficulties with 51Cr-EDTA availability have renewed interest in 99mTc-DTPA, but there is a paucity of data on the test-retest variability of this radiopharmaceutical. Furthermore, the authors are unaware of published repeatability data in cancer patients. The aim of this study was to determine the CV of repeat 99mTc-DTPA GFR measurements in a clinical patient population that included cancer patients. METHODS: Patients who had undergone ≥2 GFR studies at our department between January 2009 and December 2019 were retrospectively identified. Patients with chronic kidney disease and those who had received chemotherapy, radiotherapy or surgery between measurements were excluded. The CV for each patient was calculated and the mean CVs of cancer and prospective renal donor groups were calculated and compared. RESULTS: Fifty-four patients were included in the final analysis. The mean CV in the cancer group (38 patients) was 8.5% [95% confidence interval (CI) 6.9-10.2%] and in the renal donor group (16 patients) 7.1% (95% CI 4.2-10.1%). These figures did not differ significantly (P = 0.37). The groups were combined to calculate the final overall mean CV of 8.1% (95% CI 6.7-9.6%). CONCLUSION: In both non-cancer and cancer patients the CV of GFR studies performed with 99mTc-DTPA was comparable with mostly 51Cr-EDTA figures presented in literature.

Combined versus subtraction-only technique in parathyroid scintigraphy: effect on scan interpretation.

INTRODUCTION: Parathyroidectomy is the choice of treatment for patients with primary and tertiary hyperparathyroidism. Scintigraphic, preoperative localization of hyperfunctioning parathyroid tissue depends on either a delayed washout technique, a subtraction technique, or a combination of the two. The rationale for adopting a combination approach is its presumed superior sensitivity, but there is limited evidence to support this strategy at the cost of patient inconvenience and impact on departmental workflows. OBJECTIVE: To determine whether a combined technique detects any additional lesions during scan interpretation compared to using subtraction-only technique in patients undergoing parathyroid scintigraphy before surgery. METHODS: A retrospective analysis was performed of parathyroid scans at Tygerberg Hospital between January 2012 and April 2018. Scans were reinterpreted by consensus by three readers, blinded to the original interpretation. A McNemar discordant pairs analysis was then performed. RESULTS: A total of 97 participant scans were reviewed (female: 71; mean age: 50.8 years). The number of patients with primary, secondary, and tertiary hyperparathyroidism were 63, 21, and 13, respectively. A total of 192 lesions were identified in this study. While both combined and subtraction-only approaches identified hyperfunctioning parathyroid lesions, only four lesions were identified using the combined technique that were missed by the subtraction technique. This result was not statistically significant (P = 0.125). CONCLUSION: Based on our findings, the combined parathyroid scintigraphic technique does not improve lesion detection and may be dispensed with. Doing so will enhance patient convenience and comfort and improve departmental workflows without compromising lesion detection.

Quantitative 18F-FDG PET-CT scan characteristics correlate with tuberculosis treatment response.

BACKGROUND: There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. We used semi-automated, whole lung quantification of lung lesions to analyse serial FDG PET-CT scans from the Catalysis TB Treatment Response Cohort to identify characteristics that best correlated with clinical and microbiological outcomes. RESULTS: Quantified scan metrics were already associated with clinical outcomes at diagnosis and 1 month after treatment, with further improved accuracy to differentiate clinical outcomes after standard treatment duration (month 6). A high cavity volume showed the strongest association with a risk of treatment failure (AUC 0.81 to predict failure at diagnosis), while a suboptimal reduction of the total glycolytic activity in lung lesions during treatment had the strongest association with recurrent disease (AUC 0.8 to predict pooled unfavourable outcomes). During the first year after TB treatment lesion burden reduced; but for many patients, there were continued dynamic changes of individual lesions. CONCLUSIONS: Quantification of FDG PET-CT images better characterised TB treatment outcomes than qualitative scan patterns and robustly measured the burden of disease. In future, validated metrics may be used to stratify patients and help evaluate the effectiveness of TB treatment modalities.

Validation of Glomerular Filtration Rate Measurement with Blood Sampling from the Injection Site.

Measurement of glomerular filtration rate (GFR) from the plasma clearance of a radionuclide-labeled tracer is reliable and accurate. However, to avoid contamination of the blood samples with radioactivity remaining at the injection site, venepuncture at 2 or more sites is required: one for tracer administration and the others for blood sampling. This requirement is uncomfortable for patients, particularly when venous access is difficult. The objective of this study was to validate the use of a single site of venous access in combination with injection site imaging, for GFR measurement. Methods: Twenty-two adults (≥18 y) who were referred for GFR determination were included prospectively. GFR was measured from the plasma clearance of 99mTc-diethylenetriaminepentaacetic acid according to international guidelines. After administration of the tracer through an intravenous cannula, a 60-s static image of the injection site was acquired. A second intravenous cannula was inserted into the contralateral arm. Venous blood samples were collected at 2, 3, and 4 h after administration of the radiotracer from both the injection site (experimental) and the contralateral arm (conventional). GFR was calculated using slope-intercept and single-sample methods. The median conventional and experimental plasma counts (decay- and background-corrected) were compared for the 2-, 3-, and 4-h venous samples. Conventional and experimental GFRs were then compared, with a more than 10% difference between conventional and experimental GFRs being regarded as significant. Results: Four individuals had visible residual activity at the injection site. The median 2-h counts differed significantly between the conventional and experimental sampling sites (P = 0.007), whereas no significant difference was found at 3 or 4 h. When there was a clear injection site image, the difference between the experimental and conventional GFRs was more than 10% in 1 case for single-sample GFR but less than 8% in all cases for slope-intercept GFR. Conclusion: In cases with clear injection site images, slope-intercept GFR calculated after injection site blood sampling showed no clinically significant difference from conventional contralateral-arm sampling.

Propagation of measurement errors in glomerular filtration rate determination: a comparison of slope-intercept, single-sample and slope-only methods.

BACKGROUND: Measurement errors occurring during glomerular filtration rate (GFR) studies propagate to an error in the calculated GFR. Previous work has modelled measurement errors for slope-intercept (SI-GFR), single-sample (SS-GFR) and slope-only (SO-GFR) methods. In this study, we have extended these models. The primary aims were to (i) compare measurement errors in two-sample SI-GFR, three-sample SI-GFR, SS-GFR and SO-GFR, and (ii) determine the sensitivity of GFR to errors arising from different measurements. PATIENTS AND METHODS: This study expanded on previous models of GFR measurement error incorporating biological data from 786 patients and realistic measurement errors. GFR median absolute error and the coefficient of variation (CV) were calculated for each method. A sensitivity analysis was carried out for individual measurement errors. RESULTS: The median absolute error ranged between 1.2 and 2.3 ml/min/1.73 m, lowest for SS-GFR (4 h) and highest for SO-GFR. At higher rates of clearance, CV was less than 5% for all methods. CV increased rapidly when GFR decreased below a threshold ranging between 34 and 56 ml/min/1.73 m, lowest for three-point SI-GFR and highest for SO-GFR. SI-GFR and SS-GFR are most sensitive to injected activity quantification, but less sensitive to other measurement errors. CONCLUSION: Measurement errors are probably insignificant relative to biological variation for GFR of more than 60 ml/min/1.73 m, but become significant irrespective of biological variation at lower GFR, particularly in serial studies when GFR less than 25 ml/min/1.73 m. Limits of precision recommended in the 2018 British Nuclear Medicine Society guideline are appropriate for once-off GFR measurement, whereas slightly more stringent limits are proposed for serial studies.

The contribution of bone SPECT to the diagnosis of bone metastases in an African population.

BACKGROUND: A number of studies have demonstrated the value of performing spinal SPECT in addition to planar scintigraphy for the diagnosis of bone metastases. This has not been demonstrated in an African population, however, where patients typically present with more advanced disease. AIM: To investigate the contribution of bone SPECT to the diagnosis of bone metastases in an African population. METHODS: In a retrospective survey the studies of all patients with known primary tumours who underwent skeletal scintigraphy for the diagnosis of bone metastases during one calendar year were reviewed. The studies of patients who underwent both planar imaging and SPECT were reinterpreted. Blinded to the SPECT study, the planar studies were graded for probability of metastatic disease using a four-point scale, and the number of spinal lesions was noted. This was repeated with the planar and SPECT studies reviewed together. The interpretation using the planar images alone was compared with that obtained after the addition of SPECT using non-parametric tests. Of a total of 576 patients, 119 (45 men and 74 women) underwent planar and SPECT imaging. RESULTS: The addition of SPECT resulted in a significant change in the interpretation of these studies (P<0.05), and a significantly lower proportion of patients had equivocal gradings (P<0.01). However, the actual numbers of patients affected was relatively small, varying from six to 21, representing about 5-18% of the 119 patients who underwent an additional SPECT. Furthermore, of the total population of 576 patients with known malignancies undergoing bone scintigraphy for bone metastases, the availability of SPECT only resulted in an altered classification in 1-4%. Equivocal planar gradings were far more likely to be altered following the addition of SPECT. The addition of SPECT also resulted in the detection of significantly more spinal lesions (P<0.01). CONCLUSION: In a setting where SPECT is not easily available, planar imaging alone is still adequate in the vast majority of cases.

Nuclear Neuroimaging in Social Anxiety Disorder: A Review.

In psychiatric research, nuclear imaging complements MRI. A recent neuroimaging review of social anxiety disorder focused predominantly on MRI, omitting the contribution of nuclear imaging methods. Nuclear imaging investigations of neural activity are sparse but have generally yielded results consistent with studies performed using MRI. Evidence for disturbances in neurotransmitter systems in social anxiety disorder is limited but suggestive of both serotonergic and dopaminergic dysfunction. Research focusing on additional molecular targets using existing and novel tracers, combined with recent technologic innovations and trends in collaborative methodology, may shape future nuclear imaging endeavors in this field.

A semi-automatic technique to quantify complex tuberculous lung lesions on 18F-fluorodeoxyglucose positron emission tomography/computerised tomography images.

BACKGROUND: There is a growing interest in the use of 18F-FDG PET-CT to monitor tuberculosis (TB) treatment response. However, TB causes complex and widespread pathology, which is challenging to segment and quantify in a reproducible manner. To address this, we developed a technique to standardise uptake (Z-score), segment and quantify tuberculous lung lesions on PET and CT concurrently, in order to track changes over time. We used open source tools and created a MATLAB script. The technique was optimised on a training set of five pulmonary tuberculosis (PTB) cases after standard TB therapy and 15 control patients with lesion-free lungs. RESULTS: We compared the proposed method to a fixed threshold (SUV > 1) and manual segmentation by two readers and piloted the technique successfully on scans of five control patients and five PTB cases (four cured and one failed treatment case), at diagnosis and after 1 and 6 months of treatment. There was a better correlation between the Z-score-based segmentation and manual segmentation than SUV > 1 and manual segmentation in terms of overall spatial overlap (measured in Dice similarity coefficient) and specificity (1 minus false positive volume fraction). However, SUV > 1 segmentation appeared more sensitive. Both the Z-score and SUV > 1 showed very low variability when measuring change over time. In addition, total glycolytic activity, calculated using segmentation by Z-score and lesion-to-background ratio, correlated well with traditional total glycolytic activity calculations. The technique quantified various PET and CT parameters, including the total glycolytic activity index, metabolic lesion volume, lesion volumes at different CT densities and combined PET and CT parameters. The quantified metrics showed a marked decrease in the cured cases, with changes already apparent at month one, but remained largely unchanged in the failed treatment case. CONCLUSIONS: Our technique is promising to segment and quantify the lung scans of pulmonary tuberculosis patients in a semi-automatic manner, appropriate for measuring treatment response. Further validation is required in larger cohorts.

Resting functional connectivity in social anxiety disorder and the effect of pharmacotherapy.

Neuroimaging research has reported differences in resting-state functional connectivity (RFC) between social anxiety disorder (SAD) patients and healthy controls (HCs). Limited research has examined the effect of treatment on RFC in SAD. We performed a study to identify differences in RFC between SAD and HC groups, and to investigate the effect of pharmacotherapy on RFC in SAD. Seed-based RFC analysis was performed on technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) SPECT scans using a cross-subject approach in SPM-12. Seeds were chosen to represent regions in a recently published network model of SAD. A second-level regression analysis was performed to further characterize the underlying relationships identified in the group contrasts. Twenty-three SAD participants were included, of which 18 underwent follow-up measures after an 8-week course of citalopram or moclobemide. Fifteen healthy control (HC) scans were included. SAD participants at baseline demonstrated several significant connectivity disturbances consistent with the existing network model as well as one previously unreported finding (increased connectivity between cerebellum and posterior cingulate cortex). After therapy, the SAD group demonstrated significant increases in connectivity with dorsal anterior cingulate cortex which may explain therapy-induced modifications in how SAD sufferers interpret emotions in others and improvements in self-related and emotional processing.

Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography.

Tuberculosis is classically divided into states of latent infection and active disease. Using combined positron emission and computed tomography in 35 asymptomatic, antiretroviral-therapy-naive, HIV-1-infected adults with latent tuberculosis, we identified ten individuals with pulmonary abnormalities suggestive of subclinical, active disease who were substantially more likely to progress to clinical disease. Our findings challenge the conventional two-state paradigm and may aid future identification of biomarkers that are predictive of progression.

Opsoclonus-myoclonus in an HIV-infected child on antiretroviral therapy--possible immune reconstitution inflammatory syndrome.

The exact immunopathogenesis and neuroanatomical localization of opsoclonus-myoclonus ataxia syndrome remains unclear. We describe a 1 year 9 month old girl who, shortly after commencement of highly active antiretroviral therapy developed opsoclonus-myoclonus syndrome and subsequently died of disseminated cytomegalovirus infection. We postulate on the etiological factors that may have played a role in the disease pathogenesis of the patient's opsoclonus-myoclonus ataxia. Immune reconstitution inflammatory syndrome was considered the most likely because of the initial CD4 depletion and the onset of symptoms shortly after initiation of antiretroviral therapy. Single photon emission computed tomography (SPECT) proved helpful by localizing the area of dysfunction to the cerebellar vermis.

Appropriate indications for positron emission tomography/computed tomography: College of Nuclear Physicians of the Colleges of Medicine of South Africa.

Individualised patient treatment approaches demand precise determination of initial disease extent combined with early, accurate assessment of response to treatment, which is made possible by positron emission tomography/computed tomography (PET/CT). PET is a non-invasive tool that provides tomographic images and quantitative parameters of perfusion, cell viability, and proliferation and/or metabolic activity of tissues. Fusion of the functional information with the morphological detail provided by CT as PET/CT can provide clinicians with a sensitive and accurate one-step whole-body diagnostic and prognostic tool, which directs and changes patient management. Three large-scale national studies published by the National Oncologic PET Registry in the USA have shown that imaging with PET changes the intended patient management strategy in 36.5% to 49% of cases, with consistent results across all cancer types. The proven clinical effectiveness and growing importance of PET/CT have prompted the College of Nuclear Physicians of South Africa, in collaboration with university hospitals, to develop a list of recommendations on the appropriate use of fluorine-18-fluorodeoxyglucose (18F-FDG) and non-18F-FDG PET/CT in oncology, cardiology, neurology and infection/inflammation. It is expected that other clinical situations will be added to these recommendations, provided that they are based upon solid clinical evidence. These recommendations are intended to offer advice regarding contemporary applications of PET/CT, as well as indicating novel developments and potential future indications. The CNP believes that these recommendations will serve an important and relevant role in advising referring physicians on the appropriate use of 18F-FDG and non-18F-FDG PET/CT. More promising clinical applications will be possible in the future, as newer PET tracers become more readily available.