Dual Time Point PET Research Articles

Glioma Biopsy Based on Hybrid Dual Time-Point FET-PET/MRI-A Proof of Concept Study.

Neuroimaging based on O-[2-(18F)fluoroethyl]-l-tyrosine (FET)-PET provides additional information on tumor grade and extent compared with MRI. Dynamic PET for biopsy target selection further improves results but is often clinically impractical. Static FET-PET performed at two time-points may be a good compromise, but data on this approach are limited. The aim of this study was to compare the histology of lesions obtained from two challenging glioma patients with targets selected based on hybrid dual time-point FET-PET/MRI. Five neuronavigated tumor biopsies were performed in two difficult cases of suspected glioma. Lesions with (T1-CE) and without contrast enhancement (T1 and T2-FLAIR) on MRI were selected. Dual time-point FET-PET imaging was performed 5–15 min (PET10) and 45–60 min (PET60) after radionuclide injection. The most informative FET-PET/MRI images were coregistered with MRI in time of biopsy planning. Five biopsy targets (three from high uptake and two from moderate uptake FET areas) thought to represent the most malignant sites and tumor extent were selected. Histopathological findings were compared with FET-PET and MRI images. Increased FET uptake in the area of non-CE locations on MRI correlated well with high-grade gliomas localized as far as 3 cm from T1-CE foci. Selecting a target in the motor cortex based on FET kinetics defined by dual time-point PET resulted in a grade IV diagnosis after previous negative biopsies based on MRI. An additional grade III diagnosis was obtained from an area of glioma infiltration with moderate FET uptake (between 1 and 1.25 SUV). These findings seem to show that dual time-point FET-PET-based biopsies can provide additional and clinically useful information for glioma diagnosis. Selection of targets based on dual time-point images may be useful for determining the most malignant tumor areas and may therefore be useful for resection and radiotherapy planning.

Dual time point [18F]FLT-PET for differentiating proliferating tissues vs non-proliferating tissues

PurposeFor differentiating tumor from inflammation and normal tissues, fluorodeoxyglucose ([18F]FDG) dual time point PET could be helpful. Albeit [18F]FLT is more specific for tumors than [18F]FDG; we explored the role of dual time point [18F]FLT-PET for discriminating benign from malignant tissues.MethodsBefore any treatment, 85 womens with de novo unifocal breast cancer underwent three PET acquisitions at 33.94 ± 8.01 min (PET30), 61.45 ± 8.30 min (PET60), and 81.06 ± 12.12 min (PET80) after [18F]FLT injection. Semiquantitative analyses of [18F]FLT uptake (SUV) were carried out on tumors, liver, bone marrow (4th thoracic vertebra (T4) and humeral head), descending thoracic aorta, muscle (deltoid), and contralateral normal breast. Repeated measures ANOVA tests and Tukey’s posttests were used to compare SUVmax of each site at the three time points.ResultsThere was a significant increase in SUVmax over time for breast lesions (5.58 ± 3.80; 5.97 ± 4.56; 6.19 ± 4.42; p < 0.0001) (m ± SD for PET30, PET60, and PET80, respectively), and bone marrow (for T4, 8.21 ± 3.17, 9.64 ± 3.66, 10.85 ± 3.63, p < 0.0001; for humeral head, 3.36 ± 1.79, 3.87 ± 1.89, 4.39 ± 2.00, p < 0.0001). A significant decrease in SUVmax over time was observed for liver (6.79 ± 2.03; 6.24 ± 1.99; 5.57 ± 1.74; p < 0.0001), muscle (0.95 ± 0.28; 0.93 ± 0.29; 0.86 ± 0.20; p < 0.027), and aorta (1.18 ± 0.34; 1.01 ± 0.32; 0.97 ± 0.30; p < 0.0001). No significant difference was observed for SUVmax in contralateral breast (0.8364 ± 0.40; 0.78 ± 0.38; 0.80 ± 0.35).Conclusion[18F]FLT-SUVmax increased between 30 and 80 min only in proliferating tissues. This could be helpful for discriminating between residual tumor and scar tissue.

Early [(18)F]florbetaben and [(11)C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimer's disease.

[(18)F]FDG is a commonly used neuronal injury biomarker for early and differential diagnosis of dementia. Typically, the blood supply to the brain is closely coupled to glucose consumption. Early uptake of the Aβ tracer [(11)C]PiB on PET images is mainly determined by cerebral blood flow and shows a high correlation with [(18)F]FDG uptake. Uptake data for (18)F-labelled Aβ PET tracers are, however, scarce. We investigated the value of early PET images using the novel Aβ tracer [(18)F]FBB in the diagnosis of Alzhimers disease (AD). This retrospective analysis included 22 patients with MCI or dementia who underwent dual time-point PET imaging with either [(11)C]PiB (11 patients) or [(18)F]FBB (11 patients) in routine clinical practice. Images were acquired 1-9min after administration of both tracers and 40-70min and 90-110min after administration of [(11)C]PiB and [(18)F]FBB, respectively. The patients also underwent [(18)F]FDG brain PET imaging. PET data were analysed visually and semiquantitatively. Associations between early Aβ tracer uptake and dementia as well as brain atrophy were investigated. Regional visual scores of early Aβ tracer and [(18)F]FDG PET images were significantly correlated (Spearman's ρ = 0.780, P < 0.001). Global brain visual analysis revealed identical results between early Aβ tracer and [(18)F]FDG PET images. In a VOI-based analysis, the early Aβ tracer data correlated significantly with the [(18)F]FDG data (r = 0.779, P < 0.001), but there were no differences between [(18)F]FBB and [(11)C]PiB. Cortical SUVRs in regions typically affected in AD on early Aβ tracer and [(18)F]FDG PET images were correlated with MMSE scores (ρ = 0.458, P = 0.032, and ρ = 0.456, P = 0.033, respectively). A voxel-wise group-based search for areas with relatively higher tracer uptake on early Aβ tracer PET images compared with [(18)F]FDG PET images revealed a small cluster in the midbrain/pons; no significant clusters were found for the opposite comparison. Early [(18)F]FBB and [(11)C]PiB PET brain images are similar to [(18)F]FDG PET images in AD patients, and these tracers could potentially be used as biomarkers in place of [(18)F]FDG. Thus, Aβ tracer PET imaging has the potential to provide biomarker information on AD pathology and neuronal injury. The potential of this approach for supporting the diagnosis of AD needs to be confirmed in prospective studies in larger cohorts.

Therapy response assessment with quantitative PET: evaluation of a shortened acquisition protocol with dynamic PET/CT

Purpose The results of SUV quantification for prediction of histopathological response in patients with oesophageal carcinoma show high variations with different accuracy. However, the routine use of a full dynamic PET is limited because of long acquisition times. We tested a shortened acquisition protocol for quantitative PET to overcome that limitation. Material and methods 13 patients with histopathologically proven oesophageal adenocarcinoma underwent a combined dynamic and static 18 F-FDG PET/CT including CT tumour perfusion (Siemens, Biograph mCT). Dynamic PET (listmode) was acquired for 60 min resulting in 38 frames from 10 to 600 sec duration for the full dynamic dataset and 2 frames each with 600 sec duration (20-30 min and 50-60 min p.i.) for dual time point PET (DTP). We evaluated the metabolic rate Ki using different models: 2-compartment irreversible model (Fit), Patlak plot and DTP (van den Hoff et al). The CT tumour perfusion protocol included the parameters blood flow, blood volume and permeability. Results

Patlak Image Estimation From Dual Time-Point List-Mode PET Data

We investigate using dual time-point PET data to perform Patlak modeling. This approach can be used for whole body dynamic PET studies in which we compute voxel-wise estimates of Patlak parameters using two frames of data for each bed position. Our approach directly uses list-mode arrival times for each event to estimate the Patlak parametric image. We use a penalized likelihood method in which the penalty function uses spatially variant weighting to ensure a count independent local impulse response. We evaluate performance of the method in comparison to fractional changes in SUV values (%DSUV) between the two frames using Cramer Rao analysis and Monte Carlo simulation. Receiver operating characteristic (ROC) curves are used to compare performance in differentiating tumors relative to background based on the dynamic data sets. Using area under the ROC curve as a performance metric, we show superior performance of Patlak relative to %DSUV over a range of dynamic data sets and parameters. These results suggest that Patlak analysis may be appropriate for analysis of dual time-point whole body PET data and could lead to superior detection of tumors relative to %DSUV metrics.

Clinical utility of integrated positron emission tomography/computed tomography imaging in the clinical management and radiation treatment planning of locally advanced rectal cancer

PurposeThe role of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in the staging and radiation treatment planning of locally advanced rectal cancer is ill defined. We studied the role of integrated PET/CT in the staging, radiation treatment planning, and use as an imaging biomarker in rectal cancer patients undergoing multimodality treatment. Methods and materialsThirty-four consecutive patients with T3-4N0-2M0-1 rectal adenocarcinoma underwent FDG-PET/CT scanning for staging and radiation treatment planning. Planned clinical management was compared before and after the addition of PET/CT information. Three radiation oncologists independently delineated CT-based gross tumor volumes (GTVCT) using clinical information and CT imaging data, as well as gradient autosegmented PET/CT-based GTVs (GTVPETCT). The mean GTV, interobserver concordance index (CCI), and proximal and distal margins were compared. The maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV), and dual-time point PET parameters were correlated with clinicopathologic endpoints. ResultsClinical management was altered by PET/CT in 18% (n = 6) of patients with clinical upstaging in 6 patients and radiation treatment planning altered in 5 patients. Of the 30 evaluable preoperative patients, the mean GTVPETCT was significantly smaller than the mean GTVCT volumes: 88.1 versus 102.8 cc (P = .03). PET/CT significantly increased interobserver CCI in contouring GTV compared with CT only-based contouring: 0.56 versus 0.38 (P < .001). The proximal and distal margins were altered by a mean of 0.4 ± 0.24 cm and −0.25 ± 0.18 cm, respectively. MTV was inversely associated with 2-year progression-free survival (PFS) and overall survival (OS): smaller MTVs (<33 cc) had superior 2-year PFS (86% vs 60%, P = .04) and OS (100% vs 45%, P < .01) compared with larger MTVs (>33 cc). SUVmax and dual-time point PET parameters did not correlate with any endpoints. ConclusionsFDG-PET/CT imaging impacts overall clinical management and is useful in the radiation treatment planning of rectal cancer patients by decreasing interobserver variability in contouring target boost volumes. Pretreatment MTV may provide useful prognostic information and requires further study.

Predicting outcomes in locally advanced rectal cancer using pretreatment FDG-PET imaging.

495 Background: FDG-PET/CT imaging has been shown to have clinical utility in the management of rectal cancers. The purpose of this study was to investigate multiple FDG-PET/CT parameters to predict for outcome after neoadjuvant chemoradiation (CRT) in patients (pts) with locally advanced rectal adenocarcinoma. Methods: We retrospectively evaluated pts with locally-advanced (T2-4, N0-2, M0) rectal adenocarcinoma treated with neoadjuvant CRT who received FDG-PET/CT scans for radiation therapy planning. We evaluated the impact of SUVmax and metabolic tumor volume (MTV, determined by using PET Edge MimVista), as well as dual-time point PET parameters of retention index (RI, difference in SUVmax between the two PET scans) and RI/time. Endpoints of pathologic complete response (pCR), tumor grade, margin status and pathologic downstaging were assessed using t-test, ANOVA or non-parametric analysis when appropriate. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan Meier estimates. Results: Of the 28 consecutive pts with FDG-PET/CT planning scans identified, 25 pts underwent surgical resection. All patients received a 5-FU based concurrent chemotherapy regimen with RT (median RT dose: 50.4 Gy). Median follow-up was 21 months. The median MTV was 45 cc. Compared to pts with a MTV&gt;45 cc, pts with a MTV &lt;45 cc had improved PFS (2-yr PFS: 86% vs. 60%, p=0.04) and improved OS (2-yr OS: 100% vs. 51%, p=0.01). The correlation between MTV and T-stage was not statistically significant (23% of pts with MTV&gt;45 had T4 tumors vs. 0% of pts with MTV&lt;45, p=0.17). MTV did not correlate with the other endpoints (pCR, tumor grade, margin status, pathologic downstaging). SUVmax did not correlate with any of the identified endpoints. Of the patients with dual-time point PET/CT scans (N=19), RI and RI/time did not correlate with any of the identified endpoints. Conclusions: Pretreatment MTV correlates with PFS and OS in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation. For pts with large MTVs, more aggressive treatment approaches should be considered. Dual-time point FDG-PET imaging does not appear to add clinical value in this patient population.

Dual Time Point PET Imaging in Head and Neck Squamous Cell Carcinoma

Dual Time Point PET Imaging in Head and Neck Squamous Cell Carcinoma Objective: Dual time point 18F-fluorodeoxyglucose -positron emission tomography (DTP-PET) is a technique which may detect malignancy more accurately than standard PET/CT imaging. Our main objective was to perform a pilot study to evaluate the characteristics of DTP-PET in primary head and neck squamous cell carcinomas (HNSCC) and lymph node metastases. Study design: Case series Setting: University hospital tertiary care center Subjects and methods: 35 patients with previously untreated HNSCC underwent preoperative PET/CT at two time points (mean 41 minute time difference) from 2007-2010. Mean and maximum standardized uptake values (SUV) were measured for the primary lesion and cervical lymph node metastases at both times points and change in SUV over time was calculated. An SUV increase of 10% was used as the threshold for positivity. Results: 30 of 35 primary tumors (86%) were positive by DTPPET with an average increase in maximum SUV of 28%. 16 of 21 lymph node metastases (76%) were positive by DTP-PET with an average increase in maximum SUV of 35%. Change in mean SUV did not correlate as well with the presence of tumor. Conclusion: 86% of primary tumors and 76% of cervical lymph node metastases showed an increase in maximum SUV over time. These findings justify further study of DTP-PET as a method of detecting tumor in initial staging and restaging of HNSCC after treatment to improve the accuracy of standard PET/CT.

Clinical Significance of F-18 FP-CIT Dual Time Point PET Imaging in Idiopathic Parkinson's Disease.

The purpose of this study was to investigate the diagnostic value of dual time point F-18 FP-CIT PET imaging in idiopathic Parkinson's disease (PD). Twenty-four patients with PD (mean age 69.6) and 18 healthy people (mean age 70.26) underwent two sequential PET/CT scans (dual time point imaging) at 90 and 210 min after F-18 FP-CIT injection. Tracer activity of region of interest was measured in the caudate, putamen and a reference region in the brain from both time points. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were obtained in the control group. The percent change in tracer activity between 90- and 210-min images was calculated. The SOR values and the percent change in tracer activity were compared between the patients and healthy control group. The SOR values for the caudate, anterior and posterior putamen at both 90- and 210-min images were significantly reduced in the patients with PD. The lowest P value was obtained for the anterior and posterior putamen (p < 0.001) at both time points. There were significant differences of the percent change in tracer activity for the anterior and posterior putamen in the two groups (p = 0.01). F-18 FP-CIT PET scans at 90 and 210 min after injection are both able to diagnose PD. Therefore, the 90-min image by itself is sufficient for diagnosing PD.

FDG uptake in brown adipose tissue—A brief report on brown fat with FDG uptake mechanisms and quantitative analysis using dual-time-point FDG PET/CT

Aims Brown adipose tissue (BAT) is a potential source of false-positive findings on [ 18F] FDG PET. In this report, we have discussed the 18F-FDG uptake mechanisms in BAT and have aimed to determine if dual time point PET imaging helps to differentiate BAT from malignant lesions. Methods Patients with dual-time-point PET/CT scans were reviewed retrospectively and 31 cases (11 males, 20 females, age: 28.6±9.7) having hypermetabolic BAT were included for this study. 18F-FDG uptake in BAT was quantitatively analyzed by maximum standardized uptake values (SUVmax), and average percent change in SUVmax of BAT between early and delayed images was calculated. Results Compared to the initial scans, 18F-FDG uptakes in BAT in delayed images were higher in 26 of the patients, and lower in one patient. In terms of body regions, 18F-FDG uptake increased in 80.6%, remained unchanged in 5.5% and decreased in 13.9% of the body regions. Mean percent change in SUVmax, including all BAT regions, was 19.8±19.1% while the mean percent increase was calculated as 69±25% in regions where progressive accumulation was observed. The increase in SUVmax correlated with the time interval between the two scans. Conclusion Physiologic 18F-FDG uptake in BAT increases over time and may mimic the behavior of malignant lesions on dual time point PET imaging. Without the exact anatomic definition of the CT scan, false positive interpretation of PET data may be possible in cases with atypical BAT.

Limitations of dual time point PET in the assessment of lung nodules with low FDG avidity

FDG PET has long shown efficacy in the evaluation of indeterminate pulmonary nodules. More recently, the use of dual time point imaging has been looked at as a means for improving sensitivity and accuracy. While initial reports were very promising, more recent results looking specifically at pulmonary lesions with low levels of FDG avidity demonstrated limitations. These lesions (initial maximum standard uptake value of less than 2.5) are of particular interest due to the fact that well-differentiated adenocarcinomas, broncheoaveolar carcinoma and carcinoid may have low FDG avidity on standard PET imaging, leading to false-negative exams. Our study retrospectively reviewed the accuracy of dual time point (DTP) FDG PET imaging to determine if it aided in the identification of malignant pulmonary nodules when initial time point imaging showed a maximum SUV of less than 2.5. 113 patients had undergone a total of 130 DTP PET/CT with 152 lesions assessed. 67 lesions were subsequently definitively diagnosed as benign or malignant based upon biopsy or imaging follow-up. Utilizing a maximum SUV increase of 10%, which optimizes our sensitivity and specificity; our results demonstrate a sensitivity of 63% and a specificity of 59%, similar to other investigators evaluating lesions with low FDG avidity. Increasing or decreasing this threshold did not improve our results, nor did the addition of lesions with maximum SUV's of 2.5 or greater on initial imaging. Specifically in nodules with low FDG avidity (max SUV < 2.5), the sensitivity was 61%, specificity 58%, and accuracy was 60%. Our findings suggest that DTP FDG PET may not be of benefit in the assessment of pulmonary nodules with maximum SUV of less than 2.5 on initial imaging.

Dual-Time F-18 FDG-PET/CT Imaging for Diagnosis of Occult Non-Hodgkin Lymphoma in a Patient With Esophageal Cancer

In this case we show the significance of dual time point PET in determining the nature of an abdominal process in a 67-year-old man with a newly diagnosed adenocarcinoma of the esophagus. Whole body PET/CT detected abnormal uptake in the distal part of the esophagus. In addition, focally increased FDG uptake was detected in the right abdomen. The late PET images of the abdomen showed an increase in the SUV resulting in this lesion being evaluated as malignant. The final pathology of the abdominal mass revealed a follicular B-Cell non-Hodgkin lymphoma grade I.

Determination of Age-Related Changes in Structure and Function of Skin, Adipose Tissue, and Skeletal Muscle With Computed Tomography, Magnetic Resonance Imaging, and Positron Emission Tomography

In this article, we report quantitative preliminary data obtained from retrospective analysis of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and combined PET-computed tomography (PET/CT) examinations in subjects ages 3 to 84 years pertaining to changes in the metabolism of skin, subcutaneous adipose tissue, visceral adipose tissue, and skeletal muscle with age, as well as age-related changes in skeletal muscle attenuation. We also propose a new method for identifying hypermetabolic brown fat on FDG-PET. Finally, we present a review of the literature regarding reported age-related structural and functional changes that occur in skin, fat, and skeletal muscle. Using FDG-PET, We evaluated 213 subjects for changes in the metabolism of skin, adipose tissue, and skeletal muscle with aging. Thirty-two separate subjects were chosen to measure maximum standardized uptake value (SUV) of hypermetabolic brown fat on dual-time point PET imaging. Finally, 15 subjects evaluated by PET/CT were selected to measure changes in metabolism and attenuation of skeletal muscle, and changes in metabolism of adipose tissue with aging. We found that skin, fat, and skeletal muscle all demonstrate significant (P < 0.05) increases in SUV with increasing age on PET imaging. Dual-time point PET imaging demonstrates increasing FDG uptake of hypermetabolic brown fat in various regions studied. Finally, our PET/CT studies revealed statistically insignificant (P > 0.05) decreases in SUV of adipose tissue with aging and the opposite trend in skeletal muscles (P > 0.05). Skeletal muscle attenuation in the various regions studied was found to significantly decrease with age (P < 0.05). Our study shows notable trends in metabolism and attenuation of skeletal muscle and metabolism of skin and adipose tissue that occur with normal aging. We hope that the methodologies and data we present here will serve as a useful starting point for those interested in conducting future prospective research on age-related changes in these structures.