Prognostic value of pretreatment tumor-to-blood standardized uptake ratio (SUR) in rectal cancer.

OBJECTIVES: The prognostic value of SUV on pretreatment F-18 FDG PET/CT imaging in patients with rectal cancer is a matter of debate. SUR is of prognostic value for survival in different cancers. In this study, we aimed to examine the potential prognostic value of SUR and other parameters in pretreatment F-18 FDG PET/CT for non-metastatic rectal cancer. METHODS: One hundred four non-metastatic rectal cancer patients who underwent pretreatment PET/CT between March 2012 and January 2018 were included in the study. Firstly, SUVmax, SUVmean, MTV, and TLG were calculated semi-automatically at the workstation. SUR was calculated as the ratio of tumor SUVmax to thoracic aorta blood SUVmean. Univariate Cox regression and Kaplan-Meier analysis were used to evaluate overall survival (OS), progression free survival (PFS), and local recurrence (LR). Then, multivariate Cox regression analysis, which included the parameters that were significant in the univariate analysis, was performed. RESULTS: Multivariate Cox regression analysis revealed that SUR was a prognostic factor for PFS. Age and T stage were prognostic factors for both OS and PFS. MTV was found to be independent risk factors for OS. CONCLUSIONS: In our study, SUR was the only F-18 FDG PET/CT parameter found to be significant for PFS. The development of new parameters can increase the prognostic value of F-18 FDG PET/CT.

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.

18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT effectively contribute to early diagnosis of infection of arteriovenous graft for hemodialysis.

OBJECTIVE: An arteriovenous graft (AVG) is indicated in hemodialysis patients with failed arteriovenous access. Early treatment of AVG infection is important because an advanced prosthetic infection leads to the removal of the prosthesis. The aim of this study was to evaluate the benefits of 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT in early detection of AVG infections. SUBJECTS AND METHODS: Fifty-one AVGs were evaluated. 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT studies were performed at intervals of 10, 20-30, and 40-50 weeks after AVG insertion. Agreement between the imaging methods and reference parameters (i.e. clinical presentation, C-reactive protein and microbiological findings on the hemodialysis cannula extracted after hemodialysis from AVG) was evaluated. RESULTS: The study results showed that focal accumulation of the radiopharmaceuticals can be considered a sign of AVG infection. At 10 weeks after AVG implantation, the focal 18F-FDG findings showed the best agreement with the reference parameters (agreement coefficients AC1 - clinical status: 0.693, CRP: 0.605, cannula microbiology: 0.518, respectively). At 20 to 30 weeks after AVG implantation, the diagnostic value of focal 99mTc-HMPAO-WBC accumulation increased (AC1 coefficients: 0.658, 0.658, 0.408) and was similar to that of focal 18F-FDG uptake (AC1s: 0.656, 0.570, 0.409). Between 40 and 50 weeks since AVG implantation, the diagnostic significance of focal 99mTc-HMPAO-WBC accumulation (AC1 coefficients: 0.771, 0.811, 0.611) slightly exceeded the diagnostic value of focal 18F-FDG accumulation (AC1 coefficients: 0.524, 0.456, 0.569). CONCLUSION: 18F-FDG PET/CT and 99mTc-HMPAO-WBC SPECT/CT can both serve as important tools contributing to early diagnosis of AVG infection.

Tissue standardized uptake value is a closer surrogate of blood fluorine-18 fluorodeoxyglucose clearance after division by blood standardized uptake value, illustrated in brain and liver.

The numerator and denominator of the left-hand side of the Gjedde-Patlak-Rutland (GPR) equation for measurement of blood fluorine-18 fluorodeoxyglucose (F-FDG) clearance into tissue (Ki) are the standardized uptake values (SUVs) of tissue and blood, respectively. The extent to which normalized time (NT) in the GPR equation exceeds real time depends on half-time of clearance of F-FDG from blood. A literature review shows that NT is fairly constant, about 100 min at 60 min postinjection of F-FDG, in keeping with our own finding of no significant difference in maximum SUV in blood 60 min postinjection of F-FDG between 39 patients with F-FDG-avid malignancy on routine PET/CT (1.74±0.31) and 21 patients with normal PET/CT (1.79±0.32), and similar blood glucose levels (BGLs). Volume of distribution (V0) in the GPR equation is ∼0.4 ml/ml for brain and ∼0.9 ml/ml for lean liver. Using these values of V0 and an NT of 100 min, we used the GPR equation to calculate Ki from our own published values of SUVliver/SUVblood and SUVbrain/SUVblood at 60 min postinjection, obtaining 0.0045 ml/min/ml for liver and 0.036 ml/min/ml for brain at BGL of 5 mmol/l. These values for Ki at this BGL are close to literature values of Ki, which for liver and brain are ∼0.0033 and ∼0.035 ml/min/ml, respectively. We conclude, therefore, that following division with blood pool SUV, tissue SUV becomes a closer surrogate of Ki. This division also eliminates the controversy over which whole body metric to use in the calculation of SUV.

Quantifying Brain [18F]FDG Uptake Noninvasively by Combining Medical Health Records and Dynamic PET Imaging Data.

Full quantification of regional cerebral metabolic rate of glucose (rCMRglu) with [18F]fluorodeoxy-glucose ([18F]FDG) positron emission tomography (PET) imaging requires measurement of an arterial input function (AIF) curve, which is obtained with an invasive arterial blood sampling procedure during the scan. We previously proposed a non-invasive simultaneous estimation (nSIME) method that quantifies binding of a PET radioligand by combining individual electronic health records information and a pharmacokinetic AIF (PK-AIF) model. Initially applied only to [11C]DASB data, in this study we validate nSIME for a different radioligand, [18F]FDG, adapting the algorithm to the specific distribution and metabolism of this radioligand. We evaluate the impact of the PK-AIF model, the number of [18F]FDG-specific soft constraints, and the type of predictive strategy. The accuracy of nSIME is then compared to a population-based approach. All analyses are conducted on 67 [18F]FDG PET scans with arterial blood data available for comparison. nSIME performance is optimal for [18F]FDG when using the PK-AIF model, two soft constraints, and an aggregate model to predict the soft constraint values. Higher correlation and lower Bland-Altman spread against gold standard rCMRglu values based on arterial blood measurements are observed for nSIME (r = 0.83, spread = 1.55) compared to the population-based approach (r = 0.77, spread = 2.12). nSIME provides a data-driven estimation of both amplitude and shape of the AIF curve at the individual level and potentially enables non-invasive quantification of PET data across radioligands, avoiding the need for arterial blood sampling.

Variations of the liver standardized uptake value in relation to background blood metabolism: An 2-[18F]Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography study in a large population from China.

To investigate the influence of background blood metabolism on liver uptake of 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) and search for an appropriate corrective method.Positron emission tomography/computed tomography (PET/CT) and common serological biochemical tests of 633 healthy people were collected retrospectively. The mean standardized uptake value (SUV) of the liver, liver artery, and portal vein (i.e., SUVL, SUVA, and SUVP) were measured. SUVL/A was calculated as SUVL/SUVA, while SUVL/P was calculated as SUVL/SUVP. SUV of liver parenchyma (SUVLP) was calculated as SUVL - .3 × (.75 × SUVP + .25 × SUVA). The coefficients of variation (CV) of SUVL, SUVL/A, SUVL/P, and SUVLP were compared to assess their interindividual variations. Univariate and multivariate analyses were performed to identify vulnerabilities of these SUV indexes to common factors assessed using serological liver functional tests.SUVLP was significantly larger than SUVL (2.19 ± .497 vs 1.88 ±â€Š.495, P < .001), while SUVL/P was significantly smaller than SUVL (1.72 ±â€Š.454 vs 1.88 ±â€Š.495, P < .001). The difference between SUVL/A and SUVL was not significant (1.83 ±â€Š.500 vs 1.88 ±â€Š.495, P = .130). The CV of SUVLP (22.7%) was significantly smaller than that of SUVL (22.7%:26.3%, P < .001), while the CVs of SUVL/A (27.2%) and SUVL/P (26.4%) were not different from that of SUVL (P = .429 and .929, respectively). Fewer variables independently influenced SUVLP than influenced SUVL, SUVL/A, and SUVL/P; Only aspartate aminotransferase, body mass index, and total cholesterol, all P-values <.05.The activity of background blood influences the variation of liver SUV. SUVLP might be an alternative corrective method to reduce this influence, as its interindividual variation and vulnerability to effects from common factors of serological liver functional tests are relatively lower than the commonly used SUVL.

Influence of scan time point and volume of intravenous contrast administration on blood-pool and liver SUVmax and SUVmean in [18F] FDG PET/CT.

AIM: To investigate the influence of scan time point and volume of intravenous contrast material in 18F-FDG PET/CT on maximum and mean standardized uptake values (SUVmax/mean) in bloodpool and liver. METHODS: In 120 patients scheduled for routine whole-body 18F-FDG PET/CT the maximum and mean standardized uptake values (SUVmax/SUVmean) in the liver and blood pool were measured after varying scan time-point (delay 0 s-140 s post injectionem) and volume of contrast material (CM; 0 ml, 80 ml, 100 ml of 300 mg/ml of Iodine). Six groups of 20 patients were investigated: (1) without intravenous CM, (2-5) injection of 100 ml CM with a delay of 80 s (2), 100 s (3), 120 s (4), 140 s (5), and 80 ml CM and a delay of 100 s (6). SUVmax, SUVmean, maximum Hounsfield units (HUmax) and average Hounsfield units (HUav) were calculated with the use of manually drawn regions of interests (ROIs) over the aortic arch and healthy liver tissue. RESULTS: SUVmax in bloodpool was significantly higher in group 3, 4 and 6 compared to group 1. Groups 2 and 5 also showed higher mean values of SUVmax, but the difference was not significant. SUVmean in bloodpool was also higher in groups 2, 3, 4, 5 and 6 compared to group 1, but the differences were only statistically significant in group 3. Both SUVmax and SUVmean in healthy liver tissue did not show significant differences when compared to the non contrast-enhanced control group. CONCLUSION: SUVmax and to a lesser extent SUVmean measured in CM enhanced FDG PET/CT in blood pool could be significantly altered in high contrast CT examinations. This should be kept in mind in PET/CT protocols and evaluation relying on SUVmax and SUVmean, for example when used in the assessment of therapy response, especially in highly vascularized tumor lesions. ZIEL:: Das Ziel dieser Studie war den Einfluss von unterschiedlichen Messzeitpunkten und Volumina bei der Gabe von intravenösem Kontrastmittel in der 18F-FDG PET/CT auf SUVmax und SUVmean im Blutpool und Lebergewebe zu untersuchen. METHODEN: In 120 Patienten, geplant für eine Ganzkörper 18F-FDG -PET/CT, wurden die maximalen und durchschnittlichen standardisierten Aufnahmewerte (SUVmax/SUVmean) in der Leber und im Blutpool, jeweils nach unterschiedlichen Messzeitpunkten (Verzögerung 0 s-140 s post injectionem) und verschiedenen Volumina von Kontrastmittel (KM; 0 ml, 80 ml, 100 ml mit einer Konzentration von 300 mg/ml Jod) gemessen. Sechs Gruppen von je 20 Patienten wurden untersucht: (1) ohne intravenöses KM, (2-5) Injektion von 100 ml KM mit einer Verzögerung von 80 s (2), 100 s (3), 120 s (4), 140 s (5), und 80 ml KM mit einer Verzögerung von 100 s (6). Es wurden jeweils die SUVmax, SUVmean, die maximalen and die durchschnittlichen Hounsfield Einheiten (HUav, HUmax) anhand manuell gezeichneter Bereiche von Interesse (ROIs) im Aortenbogen und im gesunden Lebergewebe berechnet. ERGEBNISSE: Die SUVmax im Blutpool waren im Vergleich zur Gruppe 1 signifikant höher in Gruppe 3, 4 und 6. Die Gruppen 2 und 5 zeigten ebenfalls höhere Durchschnittswerte von SUVmax, der Unterschied war jedoch nicht signifikant. Die SUVmean im Blutpool waren im Vergleich zur Gruppe 1 ebenfalls höher in den Gruppen 2, 3, 4, 5 und 6, allerdings waren die Unterschiede nur in Gruppe 3 statistisch signifikant. Im Lebergewebe zeigten sowohl SUVmax, als auch SUVmean keine signifikanten Unterschiede im Vergleich zu der nativen Kontrollgruppe. SCHLUSSFOLGERUNGEN: In der Kontrastmittel-gestützten FDG PET/CT können die SUVmax und in geringerem Ausmaß auch SUVmean im Blutpool durch Hochkontrast-CT Untersuchungen signifikant beeinflusst werden. Dies sollte bei PET/CT Protokollen bzw. Auswertungen, die auf SUVmax und SUVmean beruhen, berücksichtigt werden, zum Beispiel bei der Beurteilung des Therapieansprechens insbesondere bei stark vaskularisiertem Tumorgewebe.

Test-Retest Variability in Lesion SUV and Lesion SUR in 18F-FDG PET: An Analysis of Data from Two Prospective Multicenter Trials.

Quantitative assessment of radio- and chemotherapy response with 18F-FDG whole-body PET has attracted increasing interest in recent years. In most published work, SUV has been used for this purpose. In the context of therapy response assessment, the reliability of lesion SUVs, notably their test-retest stability, thus becomes crucial. However, a recent study demonstrated substantial test-retest variability (TRV) in SUVs. The purpose of the present study was to investigate whether the tumor-to-blood SUV ratio (SUR) can improve TRV in tracer uptake. Methods: 73 patients with advanced non-small cell lung cancer from the prospective multicenter trials ACRIN 6678 (n = 34) and MK-0646-008 (n = 39) were included in this study. All patients underwent two 18F-FDG PET/CT investigations on two different days (time difference, 3.6 ± 2.1 d; range, 1-7 d) before therapy. For each patient, up to 7 tumor lesions were evaluated. For each lesion, SUVmax and SUVpeak were determined. Blood SUV was determined as the mean value of a 3-dimensional aortic region of interest that was delineated on the attenuation CT image and transferred to the PET image. SURs were computed as the ratio of tumor SUV to blood SUV and were uptake time-corrected to 75 min after injection. TRV was quantified as 1.96 multiplied by the root-mean-square deviation of the fractional paired differences in SUV and SUR. The combined effect of blood normalization and uptake time correction was inspected by considering RTRV (TRVSUR/TRVSUV), a ratio reflecting the reduction in the TRV in SUR relative to SUV. RTRV was correlated with the group-averaged-value difference (δ) in CFmean (δCFmean) of the quantity δCF = |CF - 1|, where CF is the numeric factor that converts individual ratios of paired SUVs into corresponding SURs. This correlation analysis was performed by successively increasing a threshold value δCFmin and computing δCFmean and RTRV for the remaining subgroup of patients/lesions with δCF ≥ δCFminResults: The group-averaged TRVSUV and TRVSUR were 32.1 and 29.0, respectively, which correspond to a reduction of variability in SUR by an RTRV factor of 0.9 in comparison to SUV. This rather marginal improvement can be understood to be a consequence of the atypically low intrasubject variability in blood SUV and uptake time and the accordingly small δCF values in the investigated prospective study groups. In fact, subgroup analysis with increasing δCFmin thresholds revealed a pronounced negative correlation (Spearman ρ = -0.99, P < 0.001) between RTRV and δCFmean, where RTRV ≈ 0.4 in the δCFmin = 20% subgroup, corresponding to a more than 2-fold reduction of TRVSUR compared with TRVSUVConclusion: Variability in blood SUV and uptake time has been identified as a causal factor in the TRV in lesion SUV. Therefore, TRV in lesion uptake measurements can be reduced by replacing SUV with SUR as the uptake measure. The improvement becomes substantial for the level of variability in blood SUV and uptake time typically observed in the clinical context.

Lack of neuroinflammation in the HIV-1 transgenic rat: an [(18)F]-DPA714 PET imaging study.

BACKGROUND: HIV-associated neuroinflammation is believed to be a major contributing factor in the development of HIV-associated neurocognitive disorders (HAND). In this study, we used micropositron emission tomography (PET) imaging to quantify neuroinflammation in HIV-1 transgenic rat (Tg), a small animal model of HIV, known to develop neurological and behavioral problems. METHODS: Dynamic [(18)F]DPA-714 PET imaging was performed in Tg and age-matched wild-type (WT) rats in three age groups: 3-, 9-, and 16-month-old animals. As a positive control for neuroinflammation, we performed unilateral intrastriatal injection of quinolinic acid (QA) in a separate group of WT rats. To confirm our findings, we performed multiplex immunofluorescent staining for Iba1 and we measured cytokine/chemokine levels in brain lysates of Tg and WT rats at different ages. RESULTS: [(18)F]DPA-714 uptake in HIV-1 Tg rat brains was generally higher than in age-matched WT rats but this was not statistically significant in any age group. [(18)F]DPA-714 uptake in the QA-lesioned rats was significantly higher ipsilateral to the lesion compared to contralateral side indicating neuroinflammatory changes. Iba1 immunofluorescence showed no significant differences in microglial activation between the Tg and WT rats, while the QA-lesioned rats showed significant activation. Finally, cytokine/chemokine levels in brain lysates of the Tg rats and WT rats were not significantly different. CONCLUSION: Microglial activation might not be the primary mechanism for neuropathology in the HIV-1 Tg rats. Although [(18)F]DPA-714 is a good biomarker of neuroinflammation, it cannot be reliably used as an in vivo biomarker of neurodegeneration in the HIV-1 Tg rat.

Modeling of Tracer Transport Delays for Improved Quantification of Regional Pulmonary ¹8F-FDG Kinetics, Vascular Transit Times, and Perfusion.

¹8F-FDG-PET is increasingly used to assess pulmonary inflammatory cell activity. However, current models of pulmonary ¹8F-FDG kinetics do not account for delays in ¹8F-FDG transport between the plasma sampling site and the lungs. We developed a three-compartment model of ¹8F-FDG kinetics that includes a delay between the right heart and the local capillary blood pool, and used this model to estimate regional pulmonary perfusion. We acquired dynamic ¹8F-FDG scans in 12 mechanically ventilated sheep divided into control and lung injury groups (n = 6 each). The model was fit to tracer kinetics in three isogravitational regions-of-interest to estimate regional lung transport delays and regional perfusion. ¹³NN bolus infusion scans were acquired during a period of apnea to measure regional perfusion using an established reference method. The delayed input function model improved description of ¹8F-FDG kinetics (lower Akaike Information Criterion) in 98% of studied regions. Local transport delays ranged from 2.0 to 13.6 s, averaging 6.4 ± 2.9 s, and were highest in non-dependent regions. Estimates of regional perfusion derived from model parameters were highly correlated with perfusion measurements based on ¹³NN-PET (R² = 0.92, p < 0.001). By incorporating local vascular transports delays, this model of pulmonary ¹8F-FDG kinetics allows for simultaneous assessment of regional lung perfusion, transit times, and inflammation.

Accumulation of (18)F-FDG in the liver in hepatic steatosis.

OBJECTIVE: Nonalcoholic fatty liver disease is associated with hepatic inflammation. An emerging technique to image inflammation is PET using the glucose tracer, (18)F-FDG. The purpose of this study was to determine whether in hepatic steatosis the liver accumulates FDG in excess of FDG physiologically exchanging between blood and hepatocyte. MATERIALS AND METHODS: Hepatic FDG uptake, as SUV = [voxel counts / administered activity] × body weight), and CT density were measured in a liver region in images obtained 60 minutes after injection of FDG in 304 patients referred for routine PET/CT. Maximum SUV (region voxel with the highest count rate, SUVmax) and average SUV ( SUVave) were measured. Blood FDG concentration was measured as the maximum SUV over the left ventricular cavity (SUVLV). SUVave was adjusted for hepatic fat using a formula equating percentage fat to CT density. Patients were divided in subgroups on the basis of blood glucose (< 4, 4 to < 5, 5 to < 6, 6 to < 8, 8 to < 10, and > 10 mmol/L). Hepatic steatosis was defined as CT density less than 40 HU (n = 71). RESULTS: The percentage of hepatic fat increased exponentially with blood glucose. SUVmax / SUVLV and fat-adjusted SUVave / SUVLV but not SUVave / SUVLV correlated with blood glucose. Fat-adjusted SUVave was higher in patients with hepatic steatosis (p < 0.001) by ~0.4 in all blood glucose groups. There was a similar difference (~0.3) in SUVmax (p < 0.005) but no difference in SUVave. SUVmax / SUVLV and fat-adjusted SUVave / SUVLV correlated with blood glucose in patients with hepatic steatosis but not in those without. SUVave / SUVLV correlated with blood glucose in neither group. CONCLUSION: FDG uptake is increased in hepatic steatosis, probably resulting from irreversible uptake in inflammatory cells superimposed on reversible hepatocyte uptake.

An analysis of whole body tracer kinetics in dynamic PET studies with application to image-based blood input function extraction.

In a positron emission tomography (PET) study, the local uptake of the tracer is dependent on vascular delivery and retention. For dynamic studies the measured uptake time-course information can be best interpreted when knowledge of the time-course of tracer in the blood is available. This is certainly true for the most established tracers such as 18F-Fluorodeoxyglucose (FDG) and 15O-Water (H2O). Since direct sampling of blood as part of PET studies is increasingly impractical, there is ongoing interest in image-extraction of blood time-course information. But analysis of PET-measured blood pool signals is complicated because they will typically involve a combination of arterial, venous and tissue information. Thus, a careful appreciation of these components is needed to interpret the available data. To facilitate this process, we propose a novel Markov chain model for representation of the circulation of a tracer atom in the body. The model represents both arterial and venous time-course patterns. Under reasonable conditions equilibration of tracer activity in arterial and venous blood is achieved by the end of the PET study-consistent with empirical measurement. Statistical inference for Markov model parameters is a challenge. A penalized nonlinear least squares process, incorporating a generalized cross-validation score, is proposed. Random effects analysis is used to adaptively specify the structure of the penalty function based on historical samples of directly measured blood data. A collection of arterially sampled data from PET studies with FDG and H2O is used to illustrate the methodology. These data analyses are highly supportive of the overall modeling approach. An adaptation of the model to the problem of extraction of arterial blood signals from imaging data is also developed and promising preliminary results for cerebral and thoracic imaging studies with FDG and H2O are obtained.

Factors affecting intrapatient liver and mediastinal blood pool ¹8F-FDG standardized uptake value changes during ABVD chemotherapy in Hodgkin's lymphoma.

PURPOSE: The aim of our study was to assess the intrapatient variability of 2-deoxy-2-((18)F)-fluoro-D-glucose ((18)F-FDG) uptake in the liver and in the mediastinum among patients with Hodgkin's lymphoma (HL) treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy (CHT). METHODS: The study included 68 patients (30 men, 38 women; mean age 32 ± 11 years) with biopsy-proven HL. According to Ann Arbor criteria, 6 were stage I, 34 were stage II, 12 were stage 3 and 16 were stage 4. All of them underwent a baseline (PET0) and an interim (PET2) (18)F-FDG whole-body positron emission tomography (PET)/CT. All patients were treated after PET0 with two ABVD cycles for 2 months that ended 15 ± 5 days prior to the PET2 examination. All patients were further evaluated 15 ± 6 days after four additional ABVD cycles (PET6). None of the patients presented a serum glucose level higher than 107 mg/dl. The mean and maximum standardized uptake values (SUV) of the liver and mediastinum were calculated using the same standard protocol for PET0, PET2 and PET6, respectively. Data were examined by means of the Wilcoxon matched pairs test and linear regression analysis. RESULTS: The main results of our study were an increased liver SUVmean in PET2 (1.76 ± 0.35) as compared with that of PET0 (1.57 ± 0.31; p < 0.0001) and PET6 (1.69 ± 0.28; p = 0.0407). The same results were obtained when considering liver SUVmax in PET2 (3.13 ± 0.67) as compared with that of PET0 (2.82 ± 0.64; p < 0.0001) and PET6 (2.96 ± 0.52; p = 0.0105). No significant differences were obtained when comparing mediastinum SUVmean and SUVmax in PET0, PET2 and PET6 (p > 0.05). Another finding is a relationship in PET0 between liver SUVmean and SUVmax with the stage, which was lower in those patients with advanced disease (r (2) = 0.1456 and p = 0.0013 for SUVmean and r (2) = 0.1277 and p = 0.0028 for SUVmax). CONCLUSION: The results of our study suggest that liver (18)F-FDG uptake is variable in patients with HL during the CHT treatment and the disease course and should be considered carefully when used to define the response to therapy in the interim PET in HL.

Uncertainty in measurements of ¹8F blood concentration and its effect on simplified dynamic PET analysis.

UNLABELLED: The purpose of this study was to assess the accuracy and practicality of well counter- and thyroid probe-based methods, commonly available in nuclear medicine facilities, for measuring the concentration of (18)F-FDG in blood samples. The degree to which the accuracy of such methods influences quantitative analysis of dynamic PET scans was also assessed. METHODS: Thirty-five patients with cancer of the head and neck underwent dynamic PET imaging as part of a study intended to evaluate the utility of quantitative, image-based metrics for assessment of early treatment response. The activity in blood samples from the patients, necessary to provide an estimate of the input function for quantitative analysis, was measured both using a thyroid probe and using a well counter. Three calibration techniques were compared: single-point calibration using a standard solution for the thyroid probe (ProbePoint technique), single-point calibration using a standard solution for the well counter (WellPoint technique), and multiple-point calibration over the full range of expected blood activities for the well counter (WellCurve technique). The WellCurve method was assumed to provide the most accurate estimate of blood activity. The precision of measuring blood volume using a micropipette was also evaluated by obtaining multiple blood samples. Simplified-kinetic-analysis multiple-time-point (SKA-M) uptake rates for the primary tumor were calculated for all 35 patients using PET images and each of the 3 methods for assessing blood concentration. RESULTS: Errors in blood activity measurements ranging from -9.5% to 7.6% were found using the ProbePoint method, whereas the error range was much less (from -1.3% to 0.9%) for the WellPoint method. The precision in blood volume measurements ranged from -6% to 12% in the 10 patients assessed. The errors in blood activity and volume measurements were reflected in the SKA-M measurements in the same range. CONCLUSION: The WellPoint method provides a compromise between accuracy and clinical practicality. Random errors in both blood activity and volume measurements accumulate and may compromise parameters--such as the SKA-M estimate of tumor uptake rate--that depend not only on images but also on blood concentration data.

2-[18F]fludarabine, a novel positron emission tomography (PET) tracer for imaging lymphoma: a micro-PET study in murine models.

PURPOSE: Fludarabine has proven to be of considerable efficacy in the treatment of low-grade lymphomas. We have developed the labeling of this drug with fluorine-18 and evaluated 2-[(18)F]fludarabine as a novel positron emission tomography (PET) probe for in vivo imaging. PROCEDURES: Preclinical studies were conducted with 2-[(18)F]fludarabine, in parallel with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG), in Swiss CD-1 and CB17 severely combined immunodeficient (SCID) mice, both as tumor-free control groups, and SCID mice bearing RL lymphomas. RESULTS: In Swiss mice, micro-PET studies with 2-[(18)F]fludarabine showed a distribution restricted to the organs of excretion and the spleen, the latter being less evident in SCID animals. In lymphoma-bearing SCID mice, 2-[(18)F]fludarabine demonstrated a rapid tumor uptake over the first 20 min which subsequently plateaued and provided an improved contrast than that of [(18)F]FDG. CONCLUSION: This radiotracer merits further evaluation to establish its clinical usefulness to image low-grade lymphoma in humans in future clinical investigations.

Elevated 18F-FDG levels in blood and organs after angiotensin II receptor blocker administration: experiment in mice administered telmisartan.

UNLABELLED: Angiotensin II receptor blockers (ARBs) are a common treatment for hypertensive patients but affect renal function. In this study, the effects of ARB on (18)F-FDG distribution and excretion were examined in mice treated with telmisartan at different doses. METHODS: Male C57BL/6J mice were given telmisartan (low-dose group, 0.33 mg/kg/d; moderate-dose group, 0.66 mg/kg/d; high-dose group, 3 mg/kg/d) mixed in a high-fat diet for 20 wk. Mice on a telmisartan-free diet served as the control. At designated time points, the mice were injected with (18)F-FDG (18.5 MBq/mouse, n = 5-10/time point for each group) to examine its biodistribution. Autoradiography using kidney sections was performed to visualize (18)F-FDG excretion. Plasma blood urea nitrogen (BUN) and creatinine levels were also measured to evaluate renal function. RESULTS: Twenty-week telmisartan treatment significantly and dose-dependently increased (18)F-FDG levels in the blood (percentage injected dose per gram of tissue normalized by animal body weight: low, 0.13 ± 0.03 [P < 0.0083]; moderate, 0.15 ± 0.01 [P < 0.0083]; high, 0.15 ± 0.03 [P < 0.0083], vs. control, 0.09 ± 0.01). Significantly increased (18)F-FDG levels in organs were observed in mice in the moderate- and high-dose groups but not in the low-dose group. The plasma BUN and creatinine levels also dose-dependently increased, but they were within the reference ranges (for BUN: low, 27.00 ± 4.42 mg/dL; moderate, 28.40 ± 2.70 mg/dL; high, 39.22 ± 6.91 mg/dL [P < 0.0083], vs. control, 22.40 ± 2.80 mg/dL. For creatinine: low, 0.28 ± 0.11 mg/dL; moderate, 0.40 ± 0.07 mg/dL [P < 0.0083]; high, 0.51 ± 0.09 mg/dL [P < 0.0083], vs. control, 0.18 ± 0.04 mg/dL). The blood (18)F-FDG level positively correlated with plasma BUN (r = 0.48, P < 0.01) and creatinine (r = 0.61, P < 0.01) levels. The (18)F-FDG levels in the blood and organs returned to baseline 3 wk after cessation of telmisartan treatment. Autoradiography indicated that renal (18)F-FDG excretion was attenuated by telmisartan treatment and was reversed after treatment cessation. CONCLUSION: (18)F-FDG levels in the blood and organs were significantly increased by telmisartan treatment, indicating a potential increase in background activity on PET imaging of patients treated with ARBs. Our findings indicate the need for a careful assessment of (18)F-FDG uptake in patients treated with ARBs. A brief cessation of ARB treatment may be a potential method to avoid these effects and solve this problem.

Noninvasive estimation of the input function for dynamic mouse 18F-FDG microPET studies.

A new noninvasive estimation method for the plasma time-activity curve, i.e., input function (IF) of the tracer kinetic model in dynamic (18)F-FDG microPET mouse studies, is proposed and validated. This estimation method comprises of four steps. First, a novel constraint nonnegative matrix factorization segmentation algorithm was applied to extract the left ventricle (Lv) and myocardium (Myo) time activity curves (TACs). Second, we modeled the IF as a seven-parameter mathematical equation and constructed a dual-output model of the real TAC in Lv and Myo accounting for the partial-volume and spillover effects. Then, we fit the image-derived Lv and Myo TACs to the dual-output model to estimate the parameters of the IF. Finally, the IF was validated by comparing it to the gold standard IF while considering the delay and dispersion effects. Our method was verified based on 20 mice datasets from the Mouse Quantitation Program database, provided by UCLA. The error of the areas under the curves between the delayed and dispersed estimated IF and the gold standard IF was 7.237% ± 6.742% (r = 0.969), and the error of the (18)F-FDG influx constant Ki of the Myo was 4.910% ± 6.810% ( r = 0.992). The results demonstrated the effectiveness of the proposed method.

Improved derivation of input function in dynamic mouse [18F]FDG PET using bladder radioactivity kinetics.

PURPOSE: Accurate determination of the plasma input function (IF) is essential for absolute quantification of physiological parameters in positron emission tomography (PET). However, it requires an invasive and tedious procedure of arterial blood sampling that is challenging in mice because of the limited blood volume. In this study, a hybrid modeling approach is proposed to estimate the plasma IF of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in mice using accumulated radioactivity in urinary bladder together with a single late-time blood sample measurement. METHODS: Dynamic PET scans were performed on nine isoflurane-anesthetized male C57BL/6 mice after a bolus injection of [18F]FDG at the lateral caudal vein. During a 60- or 90-min scan, serial blood samples were taken from the femoral artery. Image data were reconstructed using filtered backprojection with computed tomography-based attenuation correction. Total accumulated radioactivity in the urinary bladder at late times was fitted to a renal compartmental model with the last blood sample and a one-exponential function that described the [18F]FDG clearance in blood. Multiple late-time blood sample estimates were calculated by the blood [18F]FDG clearance equation. A sum of four-exponentials was assumed for the plasma IF that served as a forcing function to all tissues. The estimated plasma IF was obtained by simultaneously fitting the [18F]FDG model to the time-activity curves (TACs) of liver and muscle and the forcing function to early (0-1 min) left-ventricle data (corrected for delay, dispersion, partial-volume effects, and erythrocyte uptake) and the late-time blood estimates. Using only the blood sample collected at the end of the study to estimate the IF and the use of liver TAC as an alternative IF were also investigated. RESULTS: The area under the plasma IFs calculated for all studies using the hybrid approach was not significantly different from that using all blood samples. [18F]FDG uptake constants in brain, myocardium, skeletal muscle, and liver computed by the Patlak analysis using estimated and measured plasma IFs were in excellent agreement (slope∼1; R2>0.983). The IF estimated using only the last blood sample drawn at the end of the study and the use of liver TAC as the plasma IF provided less reliable results. CONCLUSIONS: The estimated plasma IFs obtained with the hybrid method agreed well with those derived from arterial blood sampling. Importantly, the proposed method obviates the need of arterial catheterization, making it possible to perform repeated dynamic [18F]FDG PET studies on the same animal. Liver TAC is unsuitable as an input function for absolute quantification of [18F]FDG PET data.