Systematic Screening Study for the Selection of Proper Stabilizers to Produce Physically Stable Canagliflozin Nanosuspension by Wet Milling Method.

One of the crucial approaches to managing the low solubility and weak bioavailability of drugs is via nanocrystal technology. Through this technology, drug particles have an increased solubility and a faster dissolution rate due to high surface free energy, which requires an appropriate stabilizer(s) to prevent instabilities during the manufacturing process and storage of the nanosuspension. This study aimed to establish a scientific predictive system for properly selecting stabilizers or to reduce the attempts on a trial-and-error basis in the wet-milling method. In total, 42 experiments were performed to examine the effect of critical material attributes on the wettability of the drug, the saturation solubility in the stabilizer solutions or combinations thereof and the dynamic viscosity of stabilizer solutions. All data were evaluated by Minitab 19® and an optimization study was performed. The optimized formulation at a certain concentration of stabilizer combination was ground by Dyno Mill® with 0.3 mm beads for one hour. The optimized nanosuspension with a particle size of 204.5 nm was obtained in short milling time and offered 3.05- and 3.51 times better dissolution rates than the marketed drug product (Invokana® 100 mg) in pH 4.5 and pH 6.8 as non-sink conditions, respectively. The formulation was monitored for three months at room temperature and 4 °C. The parameters were 261.30 nm, 0.163, -14.1 mV and 261.50 nm, 0.216 and -17.8 mV, respectively. It was concluded that this approach might indicate the appropriate selection of stabilizers for the wet-milling process.

Assessing the Correlation Between 68Ga-PSMA-11 Renal PET Parameters and Renal Function Tests.

68Ga-prostate-specific membrane antigen (PSMA) ligands are used for prostate cancer but also show high renal cortical uptake. In this study, we aimed to assess whether there is any correlation between renal PSMA PET parameters and renal function tests using the images of prostate cancer patients. Methods: 68Ga-PSMA-11 PET/CT images of the patients with prostate cancer were retrospectively evaluated. The following PET parameters were obtained: SUVmax, SUVmean, SUVmax corrected for lean body weight, SUVmean corrected for lean body weight, volume, lean body weight--corrected total lesion glycolysis (TLGSUL), and counts of both kidneys, as well as SUVmean of the liver, blood pool, and spleen. Total TLGSUL, total volume, kidney-to-liver ratio, and kidney-to-blood pool ratio were calculated. Creatinine values were obtained, and glomerular filtration rate (GFR) was calculated using the "Modification of Diet in Renal Disease" formula. Statistical analysis was performed to understand whether there is a correlation between the above parameters and renal function tests. Results: Twenty-five patients were included in this study. GFR was significantly and positively correlated and creatinine was significantly and negatively correlated with the ratios of renal SUV to liver SUV and renal SUV to blood pool SUV. GFR was marginally positively correlated with renal SUVmean corrected for lean body weight, and creatinine was marginally negatively correlated with total TLGSUL Total renal parenchymal volume was significantly and directly (positively) associated with GFR and significantly and inversely (negatively) associated with creatinine. Conclusion: Renal 68Ga-PSMA uptake appears to be correlated with renal function tests. Our method of measuring approximate renal parenchymal volume on PET images appears to be reliable.

Renal Cortical Scarring: 68Ga-PSMA-11 PET Versus 99mTc-DMSA Scanning in a Case of Pyelonephritis.

We previously reported the 68Ga-labeled prostate-specific membrane antigen (PSMA)-11 and 99mTc-dimercaptosuccinic acid (DMSA) images of the first patient in our prospective research comparing renal 68Ga-PSMA-11 PET with 99mTc-DMSA scanning in adults with pyelonephritis. Here, we present the renal cortical 68Ga-PSMA-11 PET and 99mTc-DMSA images of our second patient, who had chronic recurring pyelonephritis and demonstrated renal parenchymal defects secondary to scarring in the kidney.

Assessing the correlation between FDG PET findings of IDC breast carcinoma and histopathology of coexisting ductal carcinoma in-situ.

BACKGROUND: Ductal carcinoma in-situ (DCIS) often coexists with invasive ductal carcinoma (IDC) of the breast. DCIS is considered as a non-obligate precursor of IDC when both coexist. 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) imaging is commonly used in the staging and follow-up assessment of breast cancer. In this study, we aimed to assess if there is any correlation between primary tumor PET and histopathology findings and histopathological features of the coexisting DCIS. MATERIAL AND METHODS: FDG PET/CT images and histopathology results of the patients with newly diagnosed breast cancer (IDC) with coexisting DCIS were analyzed in this retrospective study. The grade and size of the primary tumor and histopathological features of the coexisting DCIS (nuclear grade and architectural pattern) were obtained from the postoperative histopathology results. Maximum standardized uptake values (SUV: SUVmax and SULmax) of the primary tumor normalized by weight and lean body mass were measured. Statistical analysis was performed to assess the correlation between various parameters of IDC and DCIS. RESULTS: This study included sixty-two (62) patients with IDC-DCIS. Primary tumor grade was significantly correlated and associated with the nuclear grade of the coexisting DCIS (polychoric correlation r = 0.736, and Fisher exact test, PV < 0.001, respectively). Primary tumor SUV was not correlated with the nuclear grade and architectural pattern of the coexisting DCIS (polyserial correlation r = 0.172, PV = 0.155, and Point Bi-Serial correlation r = -0.009, PV = 0.955, respectively). Median primary tumor size was marginally significantly different among DCIS nuclear grades but it was not significantly different in comedo and non-comedo cases (Kruskal-Wallis test PV = 0.053, and Mann-Whitney U test PV = 0.890, respectively). CONCLUSIONS: Primary tumor grade is correlated with the nuclear grade of the coexisting DCIS. SUV of primary tumor does not seem to be correlated with the histopathological features of coexisting DCIS (nuclear grade and architectural pattern) but this may be further studied in a larger number of patients.

PET/CT Image Artifacts Caused by the Arms.

PET/CT images are usually obtained in the arms-up position in patients with no head and neck pathology and in the arms-down position to image the head and neck area. The arms usually cause artifacts regardless of up or down positioning. These artifacts include beam hardening, scatter, truncation, and cold areas (cold artifacts) in obese or large patients; motion artifacts; implanted-metal-object artifacts; and artifacts related to radiotracer extravasation at the injection site. In this review article, we will discuss the mechanisms of these artifacts and suggest solutions to reduce or eliminate them, such as reviewing the non-attenuation-corrected PET images, performing extended-field-of-view reconstruction, not applying scatter correction, and using software to correct beam-hardening, scatter, and truncation artifacts. We will present various PET/CT images before and after corrections for such artifacts.

Renal Cortical 68Ga-PSMA-11 PET and 99mTc-DMSA Images.

68Ga-prostate-specific membrane antigen (PSMA) ligands are novel PET radiotracers for prostate cancer. These radiotracers also localize in the normal renal cortex to a high degree and can demonstrate parenchymal defects. We recently started a prospective research study to compare 68Ga-PSMA-11 PET/CT with 99mTc-dimercaptosuccinic acid (DMSA) scan in adults with pyelonephritis. Here, we present a side-by-side comparison of renal cortical PSMA PET/CT and DMSA images of an adult patient with chronic recurring pyelonephritis. Methods: Our prospective study was approved by the Ethical Committees. DMSA images (multiple planar and SPECT) were obtained 3 h after intravenous injection of 111 MBq (3 mCi) of 99mTc-DMSA. On a separate day, we obtained PET/CT images of the kidneys 60 min after intravenous injection of 74 MBq (2 mCi) of 68Ga-PSMA-11 after the patient provided written informed consent. Results: The patient was a 46-y-old woman with history of chronic recurring pyelonephritis. Both DMSA scan and PSMA PET/CT demonstrated slight cortical thinning with mildly reduced uptake in the upper pole of the right kidney, with no significant cortical defects. There was an excellent distribution of activity in the renal cortex and better image resolution with PSMA PET than with DMSA scan. Non-attenuation-corrected PSMA PET images also showed the same findings, with reasonable image quality. Conclusion: In our first case, 68Ga-PSMA-11 PET imaging provided promising results in an adult patient with pyelonephritis. The results of our prospective study on a larger number of adult patients will provide a more accurate comparison of 68Ga-PSMA-11 PET to 99mTc-DMSA scanning in pyelonephritis.

Liver: glucose metabolism and 18F-fluorodeoxyglucose PET findings in normal parenchyma and diseases.

Liver has a complex and unique energy metabolism and plays a major role in glucose homeostasis. Liver is the main control center for glycogenesis, glycogenolysis, glycolysis and gluconeogenesis which are essential to provide energy for other tissues. Liver meets its own energy need from various sources which is mainly glucose in the fed state and fatty acids in the fasting state. In this review article, we will mainly describe the glucose metabolism of the liver, effect of various factors on 18F-fluorodeoxyglucose (FDG) activity/uptake in the normal liver and 18F- FDG positron emission tomography (PET) uptake patterns in various malignant and benign liver pathologies. Brief information on metabolomics profiling analyses in liver disorders will also be provided.

Immune Checkpoint Inhibitor-Related Adverse Effects and 18F-FDG PET/CT Findings.

Immune checkpoint inhibitor (ICI) treatments activate T cells against tumors. Activated T cells attack not only the tumor but also healthy cells, causing an autoimmune reaction in various tissues. These immune-related adverse effects (IRAEs) cause 18F-FDG uptake in various tissues due to inflammation. It is important to recognize and report these findings on 18F-FDG PET/CT studies. 18F-FDG PET helps to determine the presence, location, and severity of IRAEs. In severe cases, ICI treatments are interrupted or suspended and antiinflammatory treatments are started. 18F-FDG uptake due to IRAEs may mimic metastases or disease progression. Their presence may also help in predicting response to treatment and have prognostic implications. In this review article, we provide basic information about ICI treatments, IRAEs, and 18F-FDG PET/CT findings.

Visual versus semiquantitative analysis of 18F- fluorodeoxyglucose-positron emission tomography brain images in patients with dementia.

Various studies have reported to the superiority of semiquantitative (SQ) analysis over visual analysis in detecting metabolic changes in the brain. In this study, we aimed to determine the limitations of SQ analysis programs and the current status of 18F- fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan in dementia. 18F- FDG-PET/computed tomography (CT) brain images of 39 patients with a history of dementia were analyzed both visually and semiquantitatively. Using the visually markedly abnormal 18F- FDG-PET images as standard, we wanted to test the accuracy of two commercially available SQ analysis programs. SQ analysis results were classified as matching, partially matching and nonmatching with visually markedly abnormal studies. On visual analysis, 18F- FDG-PET showed marked regional hypometabolism in 19 patients, mild abnormalities in 8 and was normal in 12 patients. SQ analysis-1 results matched with visual analysis in 8 patients (42.1%) and partially matched in 11. SQ analysis-2 findings matched with visual analysis in 11 patients (57.8%) and partially matched in 7 and did not match in 1. Marked regional hypometabolism was either on the left side of the brain or was more significant on the left than the right in 63% of patients. Preservation of metabolism in sensorimotor cortex was seen in various dementia subtypes. Reviewing images in color scale and maximum intensity projection (MIP) image was helpful in demonstrating and displaying regional abnormalities, respectively. SQ analysis provides less accurate results as compared to visual analysis by experts. Due to suboptimal image registration and selection of brain areas, SQ analysis provides inaccurate results, particularly in small areas and areas in close proximity. Image registration and selection of areas with SQ programs should be checked carefully before reporting the results.

Assessing PET Parameters in Oncologic 18F-FDG Studies.

PET imaging, particularly oncologic applications of 18F-FDG, has become a routine diagnostic study. To better describe malignancies, various PET parameters are used. In 18F-FDG PET studies, SUVmax is the most commonly used parameter to measure the metabolic activity of the tumor. In obese patients, SUV corrected by lean body mass (SUL), and in pediatric patients, SUV corrected by body surface area, are recommended. Metabolic tumor volume is an important parameter to determine the local and total tumor burden. Total lesion glycolysis (SUVmean × metabolic tumor volume) provides information about averages. Some treatment response assessment protocols recommend using the SUVpeak or SULpeak of the tumor. Tumor-to-liver ratio and tumor-to-blood-pool ratio are helpful when comparing studies for treatment response assessment. Dual-time-point PET imaging with retention index can help differentiate malignant from benign lesions and may help detect small lesions. Dynamic 18F-FDG PET imaging and quantitative analysis can measure the metabolic, phosphorylation, and dephosphorylation rates of lesions but are mainly used for research purposes. In this article, we will review the currently available PET parameters in 18F-FDG studies with their importance, uses, limitations, and reasons for erroneous results.

99mTc-dimercaptosuccinic acid scan versus MRI in pyelonephritis: a meta-analysis.

PURPOSE: Tc-dimercaptosuccinic acid (DMSA) scan is the current gold standard in detecting parenchymal changes, particularly scarring, in pyelonephritis. Recently, magnetic resonance imaging (MRI) is gaining popularity in the diagnosis of pyelonephritis. The aim of this study is to perform a meta-analysis on studies directly comparing MRI to DMSA scan in patients with pyelonephritis. MATERIALS: Systematic searches of PUBMED and EMBASE databases were performed to extract studies comparing MRI and DMSA scan in patients with pyelonephritis. The relevance of articles was assessed by two authors according to predefined inclusion and exclusion criteria. The pooled estimates of the sensitivities of MRI and DMSA scan were computed using random-effects meta-analysis model following DerSimonian and Laird's method. Subgroup analysis and publication bias were performed. RESULTS: Seven studies were included (164 patients). Using random effect model, the pooled estimate of the sensitivities of MRI and DMSA scan were 0.62 (95%CI: 0.44 - 0.77) and 0.59 (95%CI: 0.48 - 0.70), respectively. The pooled estimates of sensitivities of MRI and DMSA scan for acute pyelonephritis were 0.73 (95%CI: 0.49- 0.89) and 0.66 (95%CI: 0.56 - 0.75), respectively, and for scar detection were 0.48 (95%CI: 0.31- 0.66), and 0.50 (95%CI: 0.30 - 0.71), respectively. CONCLUSION: The overall sensitivities of MRI and DMSA scan were equivalent in detecting parenchymal changes in pyelonephritis. MRI and DMSA scan appeared to be equivalent to scar detection. In a small number of studies, MRI appeared to be better than the DMSA scan in acute pyelonephritis but this should be further studied in a larger number of patients.

Revisiting Weight-Normalized SUV and Lean-Body-Mass-Normalized SUV in PET Studies.

SUV normalized by total body weight is affected by the amount of body fat. The SUV of normal tissues and lesions is higher (overestimated) in obese patients than in patients with a normal body mass index (BMI). SUL (SUV normalized by lean body mass [LBM]) is recommended for more accurate SUV results. Given the importance of a quantitative PET parameter, particularly when comparing PET studies, we aimed to revisit the effect of obesity on SUV, measuring SUL in normal-BMI patients and obese patients and testing the effect of the amount of LBM. Methods: 18F-FDG whole-body images of adult patients were analyzed retrospectively. We measured both SUVmax and SUVmean in the blood pool and liver of patients with a normal BMI (18.5-24.9) and a high BMI (≥30) (obese). In all patients, we calculated LBM via an equation using patient height and weight and corrected all SUVs to SULs. Mean (±SD) SUVs and SULs were compared under various circumstances. Scatterplots were generated for weight and SUV-SUL differences. Results: SUVmean in the liver and blood pool was significantly higher in obese patients (30 patients) than in patients with a normal BMI (20 patients) (4.1 ± 0.7 and 3.0 ± 0.5, respectively, in liver, vs. 3.2 ± 0.6 and 2.4 ± 0.4, respectively, in blood pool; P < 0.001). SULmean was significantly lower in both liver and blood pool in all patients, being approximately 75% of SUVmean in patients with a normal BMI and 55% of SUVmean in obese patients (P < 0.001). SULmean in the liver and blood pool did not significantly differ between obese patients and normal-BMI patients (P > 0.05). The SUV-SUL difference was significantly higher in obese patients than in patients with a normal BMI (P < 0.001). These statistical results were the same when SUVmax and SULmax were compared. Conclusion: SUV overestimates metabolic activity in all patients, and this overestimation is more significant in obese patients than in patients with a normal BMI. SUL is not affected by body weight or the amount of LBM.

Assessing oral glucose and intravenous insulin loading protocol in 18F-fluorodeoxyglucose positron emission tomography cardiac viability studies.

Oral glucose and intravenous insulin (G/I) loading protocols are commonly used in 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) cardiac viability studies. Although the amount of insulin to be given per blood glucose range has been well described in guidelines, the amount of glucose to be given is not detailed well. In this retrospective study, we aimed to assess if certain parameters, particularly the amount of glucose and insulin given, may affect 18F-FDG uptake in the hibernating myocardium and also determine the problems with this protocol. 18F-FDG PET cardiac viability study with G/I loading protocols was performed in 49 patients. Fasting blood glucose (FBG), amount of glucose given, blood glucose level after glucose load, amount of insulin given, and blood glucose level at the time of 18F-FDG injection were recorded. Statistical analysis was performed to determine if there is any difference in the above values in PET viable and PET nonviable groups and also in subgroups assessing 18F-FDG uptake also in normal myocardium. For G/I loading, we used our local protocol in 43 patients, and other protocols in six. 18F-FDG PET showed viability in 31 patients, and it was negative for viability in 18. In 22 patients, mainly in PET viable group, there was varying degree of reduced 18F-FDG uptake in normal myocardium. There was no significant difference in FBG, amount of glucose given, blood glucose level after glucose load, amount of insulin given, and blood glucose level at the time of 18F-FDG injection in PET viable and PET nonviable groups and also in subgroups. The problems with G/I loading protocol included deciding on the amounts of glucose and insulin given, maximum amount of insulin to be given, handling diabetics, optimal time to measure blood glucose after insulin administration, and interpretation of findings in cases with diffusely reduced 18F-FDG uptake. Further improvements in current guidelines are necessary to obtain images in optimal conditions for accurate results.

Is there a difference in FDG PET findings of invasive ductal carcinoma of the breast with and without coexisting DCIS?

OBJECTIVES: Studies have reported that invasive ductal carcinoma (IDC) with coexisting ductal carcinoma in situ (DCIS) show lower metastatic potential and recurrence and better overall survival than pure IDC. In this study, we assessed F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images of patients with newly diagnosed IDC to determine if there is any difference in PET findings in IDC-DCIS and pure IDC cases. METHODS: FDG PET/CT images of patients with newly diagnosed IDC of the breast who subsequently underwent breast surgery and had histopathology result in our records were further evaluated. Tumor grade, pathological staging, and presence of DCIS were noted from the histopathology results. Standardized uptake value (SUV) of the primary tumor (SUVmax and SULmax), other hypermetabolic foci in the breast, and ipsilateral normal breast were measured. Presence of axillary and distant metastases was noted. RESULTS: Fifty seven (57) patients with IDC were included. Coexisting DCIS was present in 44 (IDC-DCIS) and not present in 13 (pure IDC) cases. Per histopathology, the primary tumor was unifocal in 33 IDC-DCIS (75%) and 12 pure IDC (92.3%) cases, and multifocal in 11 IDC-DCIS cases (25%), and 1 pure IDC case (7.7%). FDG uptake was multifocal in 20 IDC-DCIS cases (45.5%) and 1 pure IDC case (7.7%), and unifocal in 24 IDC-DCIS (54.5%), and 12 pure IDC (92.3%) cases. There was no significant difference in patient age, size of the primary tumor, SUVmax and SULmax of the primary tumor and SUVmax of the normal breast in IDC-DCIS and pure IDC cases (p>0.05). Pathology showed axillary metastasis in all 13 pure IDC (100%), and 27 IDC-DCIS (61.4%) cases. PET showed axillary uptake in 25 IDC-DCIS (56.8%), and 8 pure IDC (61.5%) cases, and abnormal/questionable distant uptake in 12 IDC-DCIS cases and 1 pure IDC case. CONCLUSION: In our preliminary findings, multifocal breast FDG uptake and multifocal tumor appear to be more common in IDC-DCIS than pure IDC. There is no significant difference in SUV and size of the primary tumor in IDC-DCIS and pure IDC cases. Axillary metastases appear to be more common in pure IDC than IDC-DCIS cases.

Assessing 18F-FDG Uptake in the Sentinel Lymph Node in Breast Cancer.

18F-FDG PET/CT has limited value in early breast cancer. Sentinel lymph node (SLN) biopsy is the current procedure of choice to search for small metastatic deposits in the axillary lymph nodes in early breast cancer. In this retrospective study, we reevaluated 18F-FDG PET/CT images after locating the SLN on PET/CT with the help of SLN SPECT/CT images and assessed 18F-FDG uptake, particularly in the SLN. Our goal was to understand if combined evaluation of 18F-FDG PET/CT and SLN SPECT/CT could be useful for detecting early lymph node metastasis in the axilla. Methods: 18F-FDG PET/CT images of newly diagnosed breast cancer patients who also had SLN scintigraphy (SPECT/CT) and biopsy results were analyzed to assess 18F-FDG uptake in the SLN. The SLN seen on SPECT/CT images was located on PET/CT images, and its metabolic activity was assessed both visually and semiquantitatively using SUVmax 18F-FDG PET results were compared with the histopathology result for the SLN. Results: Twenty patients among 130 met the inclusion criteria. SLN SPECT/CT images were helpful for locating the SLN on 18F-FDG PET/CT images in all 20 patients. Histopathologic analysis of the SLNs demonstrated metastasis in 7 patients and no metastasis in 13. There was mild (visible) 18F-FDG uptake in the SLN (SUVmax, 1.2-4.1; metastatic deposit size, 6-8 mm) in 6 of 7 patients with SLN metastasis (85.7%). There was no or only faint 18F-FDG uptake in the SLN (SUVmax < 1) in 9 of 13 patients with no SLN metastasis (69.2%). Receiver-operating-characteristic curve analysis indicated that the SUVmax cutoff for differentiating SLN-positive from -negative cases was 0.85 (sensitivity, 85.7%; specificity, 61.5%; area under the curve, 0.747; P < 0.05). Conclusion: Combined evaluation of 18F-FDG PET/CT and SPECT/CT images to assess 18F-FDG uptake, particularly in the SLN, is a new image analysis technique to detect early metastatic disease in the axillary lymph nodes in breast cancer. Although this technique does not currently seem feasible for use in routine practice, mainly because of the limitations of current PET/CT technology in detecting small tumors, it is an interesting image analysis technique to be aware of for possible future use.

Current Status of Radionuclide Renal Cortical Imaging in Pyelonephritis.

Pyelonephritis is an infection of the kidneys that is seen more commonly in children than the adults. 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scanning is a radionuclide imaging study to detect renal scarring after acute pyelonephritis (a late 99mTc-DMSA scan) and also helps to diagnose acute pyelonephritis in febrile urinary tract infections (an acute 99mTc-DMSA scan). Planar imaging in multiple views (posterior and bilateral posterior oblique) is generally used. Pinhole imaging with a high-resolution-collimator magnification of each kidney allows detection of smaller cortical defects. SPECT is optional. SPECT/CT is not recommended in children because it has a higher radiation exposure than routine 99mTc-DMSA scans. The main limitations of 99mTc-DMSA scanning include a relatively long waiting time after radiotracer injection, a long acquisition time, and a high radiation dose, which is particularly important in repeated studies on children and with the limited spatial resolution of γ-cameras. 99mTc-glucoheptonate is an alternative radiotracer when 99mTc-DMSA is not available. Radiotracers for dynamic renal functional imaging can grossly assess the renal cortex in the first few minutes of imaging. 68Ga-prostate-specific membrane antigen ligand (68Ga-PSMA ligand) PET has the ability to provide images of normal renal cortex and demonstrate renal cortical defects from cysts. In this article, we assess the current status of renal cortical imaging and present 68Ga-PSMA ligand PET images. 68Ga-PSMA ligand provides excellent renal cortical images, and studies should be done to compare 68Ga-PSMA ligand PET with 99mTc-DMSA scanning in renal diseases, particularly in pyelonephritis.

Assessing the Effect of Various Blood Glucose Levels on 18F-FDG Activity in the Brain, Liver, and Blood Pool.

Studies have extensively analyzed the effect of hyperglycemia on 18F-FDG uptake in normal tissues and tumors. In this study, we measured SUV in the brain, liver, and blood pool in normoglycemia, hyperglycemia, and hypoglycemia to understand the effect of blood glucose on 18F-FDG uptake and to develop a formula to correct SUV. Methods: Whole-body 18F-FDG PET/CT images of adults were selected for analysis. Brain SUVmax, blood-pool SUVmean, and liver SUVmean were measured at blood glucose ranges of 61-70, 71-80, 81-90, 91-100, 101-110, 111-120, 121-130, 131-140, 141-150, 151-160, 161-170, 171-180, 181-190, 191-200, and 201 mg/dL and above. At each blood glucose range, 10 PET images were analyzed (total, 150). The mean (±SD) SUV of the brain, liver, and blood pool at each blood glucose range was calculated, and blood glucose and SUV curves were generated. Because brain and tumors show a high expression of glucose transporters 1 and 3, we generated an SUV correction formula based on percentage reduction in brain SUVmax with increasing blood glucose level. Results: Mean brain SUVmax gradually decreased with increasing blood glucose level, starting after a level of 110 mg/dL. The approximate percentage reduction in brain SUVmax was 20%, 35%, 50%, 60%, and 65% at blood glucose ranges of 111-120, 121-140, 141-160, 161-200, and 201 mg/dL and above, respectively. In the formula we generated, measured SUVmax is multiplied by a reduction factor of 1.25, 1.5, 2, 2.5, and 2.8 for the blood glucose ranges of 111-120, 121-140, 141-160, 161-200, and 201 mg/dL and above, respectively, to correct SUV. Brain SUVmax did not differ between hypoglycemic and normoglycemic patients (P > 0.05). SUVmean in the blood pool and liver was lower in hypoglycemic patients (P < 0.05) and did not differ between hyperglycemic (P > 0.05) and normoglycemic patients. Conclusion: Hyperglycemia gradually reduces brain 18F-FDG uptake, starting after a blood glucose level of 110 mg/dL. Hyperglycemia does not affect 18F-FDG activity in the liver or blood pool. Hypoglycemia does not seem to affect brain 18F-FDG uptake but appears to reduce liver and blood-pool activity. The simple formula we generated can be used to correct SUV in hyperglycemic adults in selected cases.

Semiquantitative assessment of osteoblastic, osteolytic, and mixed lytic-sclerotic bone lesions on fluorodeoxyglucose positron emission tomography/computed tomography and bone scintigraphy.

Bone scintigraphy is widely used to detect bone metastases, particularly osteoblastic ones, and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scan is useful in detecting lytic bone metastases. In routine studies, images are assessed visually. In this retrospective study, we aimed to assess the osteoblastic, osteolytic, and mixed lytic-sclerotic bone lesions semiquantitatively by measuring maximum standardized uptake value (SUVmax) on FDG PET/computed tomography (CT), maximum lesion to normal bone count ratio (ROImax) on bone scintigraphy, and Hounsfield unit (HU) on CT. Bone scintigraphy and FDG PET/CT images of 33 patients with various solid tumors were evaluated. Osteoblastic, osteolytic, and mixed lesions were identified on CT and SUVmax, ROImax, and HU values of these lesions were measured. Statistical analysis was performed to determine if there is a difference in SUVmax, ROImax, and HU values of osteoblastic, osteolytic, and mixed lesions and any correlation between these values. Patients had various solid tumors, mainly lung, breast, and prostate cancers. There were 145 bone lesions (22.8% osteoblastic, 53.1% osteolytic, and 24.1% mixed) on CT. Osteoblastic lesions had a significantly higher value of CT HU as compared to osteolytic and mixed lesions (P < 0.01). There was no significant difference in mean ROImax and mean SUVmax values of osteolytic and osteoblastic bone lesions. There was no correlation between SUVmax and ROImax, SUVmax and HU, and ROImax and HU values in osteolytic, osteoblastic, and mixed lesions (P > 0.05). Not finding a significant difference in SUVmax and ROImax values of osteoblastic, osteolytic, and mixed lesions and also lack of correlation between SUVmax, ROImax, and HU values could be due to treatment status of the bone lesions, size of the lesion, nonmetastatic lesions, erroneous measurement of SUVmax and ROImax, or varying metabolism in bone metastases originating from various malignancies.

Gamma probes and their use in tumor detection in colorectal cancer.

The purpose of this article is to summarize the role of gamma probes in intraoperative tumor detection in patients with colorectal cancer (CRC), as well as provide basic information about the physical and practical characteristics of the gamma probes, and the radiopharmaceuticals used in gamma probe tumor detection. In a significant portion of these studies, radiolabeled monoclonal antibodies (Mabs), particularly 125I labeled B72.3 Mab that binds to the TAG-72 antigen, have been used to target tumor. Studies have reported that intraoperative gamma probe radioimmunodetection helps surgeons to localize primary tumor, clearly delineate its resection margins and provide immediate intraoperative staging. Studies also have emphasized the value of intraoperative gamma probe radioimmunodetection in defining the extent of tumor recurrence and finding sub-clinical occult tumors which would assure the surgeons that they have completely removed the tumor burden. However, intraoperative gamma probe radioimmunodetection has not been widely adapted among surgeons because of some constraints associated with this technique. The main difficulty with this technique is the long period of waiting time between Mab injection and surgery. The technique is also laborious and costly. In recent years, Fluorine-18-2-fluoro-2-deoxy-D-glucose (18F-FDG) use in gamma probe tumor detection surgery has renewed interest among surgeons. Preliminary studies during surgery have demonstrated that use of FDG in gamma probe tumor detection during surgery is feasible and useful.

Current Status of 18F-FDG PET Brain Imaging in Patients with Dementia.

18F-FDG PET brain imaging is commonly used in the early detection and differential diagnosis of various subtypes of dementias. 18F-FDG PET images are mainly evaluated visually, and semiquantitative analysis programs are also commonly used in many centers. However, visual and semiquantitative analysis carry certain limitations. Visual assessment is subjective and dependent on expertise. Commercially available semiquantitative analysis programs have certain limitations such as suboptimal selection of brain areas or erroneous uptake normalization procedures that may provide inaccurate results, and physicians reporting semiquantitative results should be aware of these. In this pictorial review article, we will discuss the current status of 18F-FDG PET brain imaging in patients with dementia and present figures and semiquantitative analysis results of various subtypes of dementias as well as certain artifacts seen on 18F-FDG PET brain imaging studies.