Change In Standardized Uptake Value Research Articles

Bone metabolism of residual ridge beneath the denture base of an RPD observed using NaF-PET/CT

A 66-year-old woman, who had a bilateral free-end edentulous mandible and no experience with dentures, was examined for the chief complaint of masticatory dysfunction on left side of dental arch. A unilateral distal extension removable partial denture (RPD) replacing lower-left molars was selected. Tomographic images were obtained using Fluorine-18 NaF positron emission computerized tomography (NaF-PET)/computed tomography (CT) before the RPD use and at 1, 6, and 13 weeks after the RPD use to observe the metabolic changes in residual bone caused by the RPD use. PET standardized uptake values (SUVs) and CT values were calculated for lower-left edentulous site (test side) and lower-right edentulous site (control side). As a result, SUVs on the control side remained static after the RPD use, whereas those on the test side increased at 1 and 6 weeks after the RPD use and then decreased. However, CT images showed no obvious changes in the bone shape and structure beneath RPD, and CT values both on the control and test sides did not change either. This report shows that NaF-PET could detect bone metabolic changes soon after the RPD use, which cannot be detected by clinical X-rays. The SUV changes may be a mechanobiological reaction to the pressure due to the RPD use, and wearing of the RPD may increase the bone turnover beneath denture. This report demonstrates that wearing of an RPD increases bone turnover beneath denture immediately after the RPD use without clinically detectable changes in bone structure or volume.

SU‐E‐J‐95: Evaluation of Repeat Respiratory Gated PET Scans for the Assessment of Treatment Effectiveness

Purpose: Gated (4D) PET/CT scans have been shown to be effective in recovering the signal lost due to respiratory motion. Ungated (3D) and 4D FDG‐PET scans obtained pre and post radiation therapy (RT) for lung cancer were compared to examine the role of 4D PET in assessing FDG uptake changes due to therapy. Methods: Sequential 3D and 4D FDG‐PET/CT scans were acquired approximately two weeks before (pre‐RT) and one month after (post‐RT) treatment for patients receiving definitive RT for lung cancer. Targeted lesions were identified for each patient, and a region of interest (ROI) was defined for each lesion on the 3D and each of the five phases of the 4D pre‐RT scans. The ROIs were generated using a 40% of the maximum standardized uptake value (SUV) threshold, and the maximum SUV for each lesion from the pre—RT scans was recorded. Pre‐RT ROIs were then used to locate the areas of the original FDG uptake on the post‐RT scans using rigid registration. A post‐RT ROI was generated, and the maximum post‐RT SUV was recorded. Results: Sixteen lesions were identified and analyzed for twelve patients. Comparison of pre‐RT to post‐RT 3D PET scans showed a median SUV decrease of 62% (range 36–89%), while comparison of pre‐RT to post‐RT 4D PET scans showed a median SUV decrease of 67% (range 30–89%). The mean difference between the SUV change on 3D versus 4D scans was 4.9% (range 0–15%, p=.07), and the highest quartile had an absolute difference greater than 9% in SUV change.Conclusion: When assessing SUV changes with PET scans done pre and post‐RT, a substantial proportion of lesions had showed differences of over 9% in measurement of SUV change when comparing 3D PET to 4D PET. Such differences could potentially influence classification of PET‐based response assessment.

TU‐C‐211‐09: Quantitative Total Bone Imaging Methodology and Its Sensitivity to Thresholding

Purpose: Prostate cancer is the most prevalent cancer among males in the US, and over 90% of patients develop bone metastases. Current treatment response evaluation metrics, such as RECIST, are not suited for assessing bone lesions. The aim of this work is to present an automated segmentation method that identifies and characterizes bone lesions and determine its sensitivity to thresholding. Methods: Patients with metastatic prostate cancer were treated with molecular target therapy and received whole body [F‐18]NaF (bone imaging) PET/CT scans during the course of treatment. Scans were evaluated using the Quantitative Total Bone Imaging (QTBI) methodology, which assesses total bone and individual bone lesions in patients with bone metastases. Individual lesions were segmented using thresholds ranging from 20% to 80% of the maximum standardized uptake value (SUV) in bone. The mean SUV, total SUV, and volume of the total bone and individual lesions were determined as well as the number of lesions. Treatment response was assessed as the percent change in the imaging metrics relative to pre‐treatment. Results: The QTBI methodology was able to identify and characterize bone lesions. Of the treatment response metrics, change in number of lesions showed the greatest dependence on the threshold. The standard deviation of patient responses ranged from 13.5 to 34.5. Change in mean SUV had the least sensitivity to threshold (SD=0.5–2.0). Change in total SUV and volume both showed intermediate variation (SD=7.5–11.5 and 11.0–12.5, respectively). Conclusions: The QTBI methodology is able to identify and characterize bone lesions. However, because most imaging metric responses vary with different thresholds, careful selection of SUV threshold for segmentation is necessary to accurately identify and characterize bone lesions and assess treatment response. With further refinement, this methodology can be a clinically useful tool to improve patient care and test new therapies for use in metastatic bone disease.

Standard uptake value and metabolic tumor volume of 18F-FDG PET/CT predict short-term outcome early in the course of chemoradiotherapy in advanced non-small cell lung cancer

The aim of this study is to investigate the role of standard uptake values (SUVs) and metabolic tumor volume (MTV) in [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to predict the short-term outcome of chemoradiotherapy (CRT) in patients with advanced non-small cell lung cancer (NSCLC). A total of 37 patients were included in the prospective study. All patients were evaluated by FDG PET before and following 40 Gy radiotherapy (RT) with a concurrent cisplatin-based chemotherapy regimen. Semiquantitative assessment was used to determine maximum and mean SUVs (SUV(max)/SUV(mean)) and metabolic tumor volume (MTV). Short-term outcome using the treatment response evaluation was assessed according to the Response Evaluation Criteria in Solid Tumors. The receiver-operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy of (18)F-FDG PET in identifying responders. Changes in SUV(max), SUV(mean), and MTV were significantly more pronounced in responders than in nonresponders (p = 0.002, 0.002, 0.000). The thresholds of SUV(max), SUV(mean), and MTV changes defined by ROC curve analysis were 37.2, 41.7, and 29.7%, respectively. The sensitivity, specificity, and accuracy of SUV(max) change for predicting tumor response were 83.3, 84.6, and 84.9%, respectively. The sensitivity, specificity, and accuracy of SUV(mean) change for predicting tumor response were 79.2, 100, and 88.8%, respectively. The sensitivity, specificity, and accuracy of MTV change for predicting tumor response were 91.7, 84.6, and 92.3%, respectively. SUV and MTV changes from two serial (18)F-FDG PET/CT scans, before and after initial CRT, allow prediction of the treatment response in advanced NSCLC.

Evaluation of a cumulative SUV-volume histogram method for parameterizing heterogeneous intratumoural FDG uptake in non-small cell lung cancer PET studies

PurposeStandardized uptake values (SUV) are commonly used for quantification of whole-body [18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) studies. Changes in SUV following therapy, however, only provide a proper measure of response in case of homogeneous FDG uptake in the tumour. The purpose of this study was therefore to implement and characterize a method that enables quantification of heterogeneity in tumour FDG uptake.MethodsCumulative SUV-volume histograms (CSH), describing % of total tumour volume above % threshold of maximum SUV (SUVmax), were calculated. The area under a CSH curve (AUC) is a quantitative index of tumour uptake heterogeneity, with lower AUC corresponding to higher degrees of heterogeneity. Simulations of homogeneous and heterogeneous responses were performed to assess the value of AUC-CSH for measuring uptake and/or response heterogeneity. In addition, partial volume correction and image denoising was applied prior to calculating AUC-CSH. Finally, the method was applied to a number of human FDG scans.ResultsPartial volume correction and noise reduction improved CSH curves. Both simulations and clinical examples showed that AUC-CSH values corresponded with level of tumour heterogeneity and/or heterogeneity in response. In contrast, this correspondence was not seen with SUVmax alone. The results indicate that the main advantage of AUC-CSH above other measures, such as 1/COV (coefficient of variation), is the possibility to measure or normalize AUC-CSH in different ways.ConclusionAUC-CSH might be used as a quantitative index of heterogeneity in tracer uptake. In response monitoring studies it can be used to address heterogeneity in response.

Axitinib inhibition of [18F] fluorothymidine (FLT) uptake in patients (pts) with colorectal cancer (CRC): Implications for cytotoxic chemotherapy combinations.

3591 Background: Axitinib is an oral, potent, and selective inhibitor of VEGF receptors (VEGFR) 1, 2, and 3. Clinical trials of VEGFR inhibitors in combination with cytotoxic chemotherapies have yet to yield positive results. Inhibition of cancer cell proliferation by VEGFR inhibitors may be antagonizing cytotoxic chemotherapy. This serial FLT-PET imaging study was performed to determine whether continuous dosing of axitinib inhibits FLT uptake and whether a 3- or 7-day drug holiday could reverse the FLT uptake inhibition. Methods: Pts with CRC or other GI cancers with suitable lesions were enrolled. Axitinib 7 mg (cohort 1) or 10 mg (cohort 2) twice daily (BID) starting dose was administered continuously for 7 days, then interrupted for ≥7 days. Dynamic and whole-body FLT-PET/CT scans were obtained at baseline, at the end of 7 days of continuous axitinib BID dosing, and then 3 and 7 days after axitinib interruption. Kinetic parameters calculated included the Patlak influx constant (Kpatlak) and changes in standardized uptake values (SUVmax, SUVmean). For liver lesions, SUVmean was used. Results: A total of 19 pts were enrolled, 3 and 16 into Cohorts 1 and 2, respectively. 15 had CRC and 4 had other GI cancers; 14 were male, and median age was 56 yrs. Serial FLT-PET data were available for 18 pts: 6 with lung, 5 with liver, 3 with lymph node, 2 with abdominal wall, and 2 with pelvic lesions. Following an initial 7 days of continuous axitinib, tumor FLT uptake (mean DSUV) changed by –46.0% (95% CI: –31.8%, –60.2%) from baseline. Then, after 3 days of axitinib holiday, tumor FLT uptake increased from nadir by +54.5% (95% CI: +17.5%, +91.5%), which further increased by +96.6% (95% CI: +36.4%, +156.8%) after 7 days of axitinib holiday. Conclusions: Continuous axitinib therapy for 7 days markedly inhibited fluorothymidine uptake. Since inhibition of cancer cell proliferation can protect against the cytotoxic effects of chemotherapeutics, this could explain the failure of VEGFR inhibitor + chemotherapy regimens to improve chemotherapy. Inclusion of a short drug holiday in axitinib dosing schedule may allow resensitization of cancer cells.

Quantitative diffusion weighted MRI: A functional biomarker of nodal disease in Hodgkin lymphoma?

This study explores the relationship between MRI Apparent Diffusion Coefficient (ADC) and PET Standardized Uptake Value (SUV) measurements in pediatric Hodgkin lymphoma. Sixteen patients (mean age 15.4 yrs, 8 male) with proven Hodgkin lymphoma were recruited and staged using PET-CT, anatomical MRI and additional 1.5T diffusion weighted imaging (DWI) prior to and following chemotherapy. Pre-treatment lymph nodes and anatomically paired post-treatment residual tissue located on MRI were matched to the corresponding PET-CT. Region of interest (ROI) analysis was used to extract quantitative measurements. Mean ADC (ADC(mean)) and maximum SUV (SUV(max)) were recorded and correlation assessed using Spearman statistics. Fifty-three ROIs were sampled. Pre- and post-treatment ADC(mean) ranged from 0.77 × 10(−3) to 1.79 × 10(−3) (median 1.15 × 10(−3) mm(2)s(−1)) and 1.08 × 10(−3) to 3.18 ×10(−3) (median 1.88 × 10(−3) mm(2)s(−1)), and SUV(max) from 2.60 to 25.4 (median 8.85 mg/ml) and 1.00 to 3.50 mg/ml (median 1.90 mg/ml). Median post-treatment ADC(mean) was higher, and median SUV(max) lower than pretreatment values (p < 0.0001). There was an inverse correlation between pre-treatment ADC(mean) and SUV(max) (p = 0.005) and between fractional change ([post-treatment – pre-treatment]/pre-treatment)in ADC(mean) and SUV(max) (p =0.002). Our results confirm a strong reciprocal relationship between nodal ADC(mean) and SUV(max) in Hodgkin lymphoma;supporting the potential application of quantitative DWI as a functional biomarker of disease.

PET Tumor Metabolism in Locally Advanced Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy: Value of Static versus Kinetic Measures of Fluorodeoxyglucose Uptake

Changes in tumor metabolism from positron emission tomography (PET) in locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NC) are predictive of pathologic response. Serial dynamic [(18)F]-FDG (fluorodeoxyglucose) PET scans were used to compare kinetic parameters with the standardized uptake value (SUV) as predictors of pathologic response, disease-free survival (DFS), and overall survival (OS). Seventy-five LABC patients underwent FDG PET prior to and at midpoint of NC. FDG delivery (K(1)), FDG flux (K(i)), and SUV measures were calculated and compared by clinical and pathologic tumor characteristics using regression methods and area under the receiver operating characteristic curve (AUC). Associations between K(1), K(i), and SUV and DFS and OS were evaluated using the Cox proportional hazards model. Tumors that were hormone receptor negative, high grade, highly proliferative, or of ductal histology had higher FDG K(i) and SUV values; on an average, FDG K(1) did not differ systematically by tumor features. Predicting pathologic response in conjunction with estrogen receptor (ER) and axillary lymph node positivity, kinetic measures (AUC = 0.97) were more robust predictors than SUV (AUC = 0.84, P = 0.005). Changes in K(1) and K(i) predicted both DFS and OS, whereas changes in SUV predicted OS only. In multivariate modeling, only changes in K(1) remained an independent prognosticator of DFS and OS. Kinetic measures of FDG PET for LABC patients treated with NC accurately measured treatment response and predicted outcome compared with static SUV measures, suggesting that kinetic analysis may hold advantage of static uptake measures for response assessment.

Ex vivo evaluation of the serotonin 1A receptor partial agonist [3H]CUMI‐101 in awake rats

[³H]CUMI-101 is a 5-HT(1A) partial agonist, which has been evaluated for use as a positron emission tracer in baboon and humans. We sought to evaluate the properties of [³H]CUMI-101 ex vivo in awake rats and determine if [³H]CUMI-101 can measure changes in synaptic levels of serotonin after different challenge paradigms. [³H]CUMI-101 shows good uptake and good specific binding ratio (SBR) in frontal cortex 5.18 and in hippocampus 3.18. Binding was inhibited in a one-binding-site fashion by WAY100635 and unlabeled CUMI-101. The ex vivo B(max) of [³H]CUMI-101 in frontal cortex (98.7 fmol/mg) and hippocampus (131 fmol/kg) agree with the ex vivo B(max) of [³H]MPPF in frontal cortex (147.1 fmol/mg) and hippocampus (72.1 fmol/mg) and with in vitro values reported with 8-OH-DPAT. Challenges with citalopram, a selective serotonin reuptake inhibitor, fenfluramine, a serotonin releaser, and 4-chloro-DL-phenylalanine, a serotonin synthesis inhibitor, did not show any effect on the standardized uptake values (SUVs) in any region. Citalopram did alter SBR, but this was due to changes in cerebellar SUVs. Our results indicate that [³H]CUMI-101 is a good radioligand for imaging 5-HT(1A) high-density regions in rats; however, the results from pharmacological challenges remain inconclusive.

3’-deoxy-3’-[18F]fluorothymidine PET Quantification of Bone Marrow Response to Radiation Dose

The purpose of this study was to quantify the relationship of bone marrow response to radiation dose, using 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT)-labeled uptake quantified in positron-emission tomography (PET) scans.Pre- and post-Week 1 treatment [(18)F]FLT PET images were registered to the CT images used to create the radiation treatment plan. Changes in [(18)F]FLT uptake values were measured using profile data of standardized uptake values (SUVs) and doses along the vertebral bodies located at a field border where a range of radiation doses were present for 10 patients. Data from the profile measurements were grouped into 1 Gy dose bins from 1 to 9 Gy to compare SUV changes for all patients. Additionally, the maximum pretreatment, the post-Week 1 treatment, and the dose values located within the C6-T7 vertebrae that straddled the field edge were measured for all patients.Both the profile and the individual vertebral data showed a strong correlation between SUV change and radiation dose. Relative differences in SUVs between bins >1 Gy and <7 Gy were statistically significant (p < 0.01, two-sample t test). The reduction in SUV was approximately linear until it reached a reduction threshold of 75%-80% in SUV for doses greater than 6 Gy/week for both the dose-binned data and the vertebral maximum SUVs.The change in SUV observed in head and neck cancer patients treated with chemoradiation shows the potential for using [(18)F]FLT PET images for identifying active bone marrow and monitoring changes due to radiation dose. Additionally, the change in [(18)F]FLT uptake observed in bone marrow for different weekly doses suggests potential dose thresholds for reducing bone marrow toxicity.

Predicting pathologic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer using FDG PET/CT.

505 Background: Pathologic complete response (pCR) after neoadjuvant chemoradiation has been observed in 15% to 30% of patients with locally advanced rectal cancer. The utility of FDG PET/CT scans in the management of patients with stage II or III rectal cancer is not well defined. The objective of this study is to determine if FDG PET/CT can be used to predict pCR and disease-free survival in patients receiving neoadjuvant chemoradiation with locally advanced rectal cancer. Methods: A retrospective chart review was conducted in patients with endorectal ultrasound-staged T3 to T4 rectal tumors who underwent preoperative and postoperative FGD PET/CT imaging. All patients were treated with neoadjuvant chemoradiotherapy (CRT). Maximum standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, % SUV change, and time between therapy and surgery in comparison to pathological complete response. Kaplan-Meier estimation was used to look for significant predictors of survival. Results: Seventy patients (mean age 62; 42M:28F) with preoperative stage T3Nx (n = 60) and T4Nx (n = 10) underwent pre-CRT and post-CRT FDG PET/CT scans between November 2002 and March 2009. All patients underwent definitive surgery after therapy with standard pathologic evaluation.The pCR rate was 26%. Median pre-CRT SUV was 10.5 while the median post-CRT SUV was 4.05. Patients with pCR had a lower mean post-CRT SUV compared to those without pCR (2.7 vs. 4.5, p = 0.02). Median SUV decrease was 61% (range 6% to 95%) and was significant in predicting pCR (p = 0.004). Patients with a pCR had a greater time interval between neoadjuvant therapy and surgery (median 57 days vs. 50 days) than those without (p = 0.05). Furthermore, patients with post-CRT SUV &lt; 4 had a lower local recurrence rate compared to those with post-CRT SUV &gt; 4 (p = 0.03). Patients with SUV decrease &gt; 61% had improved overall survival at mean follow-up of 39 months than those without (p = 0.01). Conclusions: PET/CT can predict response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Pre-CRT SUV was the only predictor of disease-free survival. No significant financial relationships to disclose.

Influence of dietary state and insulin on myocardial, skeletal muscle and brain [18F]-fluorodeoxyglucose kinetics in mice

BackgroundWe evaluated the effect of insulin stimulation and dietary changes on myocardial, skeletal muscle and brain [18F]-fluorodeoxyglucose (FDG) kinetics and uptake in vivo in intact mice.MethodsMice were anesthetized with isoflurane and imaged under different conditions: non-fasted (n = 7; "controls"), non-fasted with insulin (2 IU/kg body weight) injected subcutaneously immediately prior to FDG (n = 6), fasted (n = 5), and fasted with insulin injection (n = 5). A 60-min small-animal PET with serial blood sampling and kinetic modeling was performed.ResultsWe found comparable FDG standardized uptake values (SUVs) in myocardium in the non-fasted controls and non-fasted-insulin injected group (SUV 45-60 min, 9.58 ± 1.62 vs. 9.98 ± 2.44; p = 0.74), a lower myocardial SUV was noted in the fasted group (3.48 ± 1.73; p < 0.001). In contrast, the FDG uptake rate constant (Ki) for myocardium increased significantly by 47% in non-fasted mice by insulin (13.4 ± 3.9 ml/min/100 g vs. 19.8 ± 3.3 ml/min/100 g; p = 0.030); in fasted mice, a lower myocardial Ki as compared to controls was observed (3.3 ± 1.9 ml/min/100 g; p < 0.001). Skeletal muscle SUVs and Ki values were increased by insulin independent of dietary state, whereas in the brain, those parameters were not influenced by fasting or administration of insulin. Fasting led to a reduction in glucose metabolic rate in the myocardium (19.41 ± 5.39 vs. 3.26 ± 1.97 mg/min/100 g; p < 0.001), the skeletal muscle (1.06 ± 0.34 vs. 0.34 ± 0.08 mg/min/100 g; p = 0.001) but not the brain (3.21 ± 0.53 vs. 2.85 ± 0.25 mg/min/100 g; p = 0.19).ConclusionsChanges in organ SUVs, uptake rate constants and metabolic rates induced by fasting and insulin administration as observed in intact mice by small-animal PET imaging are consistent with those observed in isolated heart/muscle preparations and, more importantly, in vivo studies in larger animals and in humans. When assessing the effect of insulin on the myocardial glucose metabolism of non-fasted mice, it is not sufficient to just calculate the SUV - dynamic imaging with kinetic modeling is necessary.

Utility of fluorodeoxyglucose-positron emission tomography in the identification of new lesions in lung cancer patients for the assessment of therapy response

Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) has added positron emission tomography (PET) as an optional complement for the detection of new lesions. In this study, we evaluate the utility of fluorodeoxyglucose (FDG)-PET in the identification of new lesions and progressive disease not recognized on computed tomography (CT) in patients with nonsmall cell lung cancer (NSCLC) undergoing therapy. Seventy patients (30 female, 40 male; mean age 67±14 years, range, 39-94 years) with NSCLC underwent FDG-PET before and after chemotherapy and/or radiotherapy, whereas 69 patients underwent CT imaging. Overall (OS) and progression-free survivals (PFS) were calculated for RECIST 1.1 with CT alone, RECIST 1.1 with PET for the identification of new lesions, visual PET, and semiquantitative PET using a change in standardized uptake value ranging from -15 to -50%. PET identified new lesions in 26 patients, resulting in 10 patients (14.5%) being upgraded to progressive disease. The combination of CT and PET for the detection of new lesions improved the prediction of survival (OS: P=0.0491 for all stages and P=0.0033 for stage IV; PFS: P=0.0045 for stage IV) compared with CT imaging alone (OS: P=0.1362 for all stages and P=0.1625 for stage IV; PFS: P=0.0632 for stage IV). Furthermore, a change in standardized uptake value of -35% was the most discriminative for the prediction of survival for the semiquantitative PET approach (OS: P=0.0393 for all stages, P=0.0051 for stage IV; PFS: P=0.0092 for stage IV) and more discriminative than the visual PET approach (OS: P=0.2699 for all stages, P=0.0105 for stage IV; PFS: P=0.014 for stage IV). FDG-PET is helpful in identifying new lesions in NSCLC patients, resulting in the improved assessment of therapy response with CT imaging combined with FDG-PET compared with CT imaging alone. Although RECIST 1.1 includes FDG-PET only as an optional adjunct, we recommend the implementation of PET imaging in the assessment of therapy response.

FDG-PET Assessment of the Effect of Head and Neck Radiotherapy on Parotid Gland Glucose Metabolism

Functional imaging with [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) provides the opportunity to define the physiology of the major salivary glands before and after radiation therapy. The goal of this retrospective study was to identify the radiation dose-response relationship of parotid gland glucose metabolism in patients with head and neck squamous cell carcinoma (HNSCC). Forty-nine adults with HNSCC were identified who had curative intent intensity-modulated radiation therapy (IMRT) and FDG-PET imaging before and after treatment. Using a graphical user interface, contours were delineated for the parotid glands on axial CT slices while all authors were blinded to paired PET slices. Average and maximal standard uptake values (SUV) were measured within these anatomic regions. Changes in SUV and volume after radiation therapy were correlated with parotid gland dose-volume histograms from IMRT plans. The average parotid gland volume was 30.7 mL and contracted 3.9 ± 1.9% with every increase of 10 Gy in mean dose (p = 0.04). However, within the first 3 months after treatment, there was a uniform reduction of 16.5% ± 7.3% regardless of dose. The average SUV(mean) of the glands was 1.63 ± 0.48 pretreatment and declined by 5.2% ± 2.5% for every increase of 10 Gy in mean dose (p = 0.04). The average SUV(max) was 4.07 ± 2.85 pretreatment and decreased in a sigmoid manner with mean dose. A threshold of 32 Gy for mean dose existed, after which SUV(max) declined rapidly. Radiation dose responses of the parotid glands can be measured by integrated CT/FDG-PET scans. Retrospective analysis showed sigmoidal declines in the maximum metabolism but linear declines in the average metabolism of the glands with dose. Future studies should correlate this decline in FDG uptake with saliva production to improve treatment planning.

Positron emission tomography in patients with aggressive fibromatosis/desmoid tumours undergoing therapy with imatinib

We used (18)F-FDG PET to evaluate the FDG uptake in patients with aggressive fibromatosis (AF, also known as desmoid tumours) undergoing therapy with imatinib (imatinib mesylate, Glivec). The pilot study included nine patients with progressive AF receiving oral treatment with imatinib at a daily dose of 800 mg. Patients were examined using PET prior to the start of therapy and during imatinib treatment. Restaging according to the Response Evaluation Criteria in Solid Tumors (RECIST) was performed in parallel using CT and/or MRI and served as reference. The clinical outcomes in nine evaluable patients were as follows: seven patients with stable disease, and two patients with progressive disease. A 27% decrease in the median average standardized uptake value (SUV) of the sequential PET examinations was demonstrated in all evaluable patients with three patients (33%) showing a decrease in SUV of more than 40% (48%, 52% and 54%, respectively); no patient showed a substantial increase in SUV. To our knowledge, this is the first series of AF patients undergoing treatment with imatinib and monitored using sequential PET imaging, that allows detection of SUV changes after imatinib induction, thus helping to decide whether treatment should be continued or not.

Stability of 3′-Deoxy-3′-[18F]Fluorothymidine Standardized Uptake Values in Head and Neck Cancer Over Time

The purpose of this study was to evaluate the consistency of 3'-deoxy-3'[(18)F]fluorothymidine (FLT) standardized uptake values (SUVs) over the time course of imaging in head and neck cancer. Thirteen (13) subjects (all male; age: 56.9 +/- 6.7 years) with squamous cell head and neck cancer, stage III/IV, were administered FLT and imaged dynamically for 1 hour over the tumor and then underwent whole-body (WB) imaging commencing at 74 +/- 6 minutes. Imaging was repeated after 5 days of radiotherapy (10 Gy) and a single course of platinum-based chemotherapy. Volumes-of-interest (VOIs) were created on the last dynamic frame (SUV(60)). The pretherapy WB and midtherapy images were coregistered to the dynamic sequence and VOIs were applied. Mean and maximum SUVs (SUV(60) and SUV(WB)) and the change with treatment were evaluated. The correlations (Spearman's rho) between SUV(60) and SUV(WB) for all VOIs (pre- and midtherapy, n = 108 data pairs) were 0.98 for mean and 0.97 for maximum SUVs (p < 0.0001). Average absolute differences between SUV(60) and SUV(WB) were 0.18 +/- 0.15 and 0.29 +/- 0.32 SUV units, respectively. Correlations (Spearman's rho) between the change in SUV with therapy were 0.90 for mean and 0.89 for maximum SUV (p < 0.0001), with differences in the change values averaging 0.03 +/- 0.36 and -0.17 +/- 0.57 units, respectively. FLT SUVs are stable and comparable for images initiated between 55 and 100 minutes postinjection whether acquired pre- or midtherapy in head and neck cancer.

Impact of Dynamic 18F-FDG PET on the Early Prediction of Therapy Outcome in Patients with High-Risk Soft-Tissue Sarcomas After Neoadjuvant Chemotherapy: A Feasibility Study

Dynamic PET (dPET) studies with (18)F-FDG were performed in patients with soft-tissue sarcomas who received neoadjuvant chemotherapy early in the course of therapy. The goal of the study was to evaluate the impact of early dPET studies and assess their value with regard to the therapy outcome using histopathologic data. The evaluation included 31 patients with nonmetastatic soft-tissue sarcomas, who were treated with neoadjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin. Patients were examined before the onset of therapy and after the completion of the second cycle. Histopathologic response served for reference and was available for 25 of 31 patients. Response was defined as less than 10% viable tumor tissue in the resected tumor tissue. The following parameters were retrieved from dPET studies: standardized uptake value (SUV); fractal dimension; 2-compartment model with computation of K(1), k(2), k(3), and k(4) (unit, 1/min); fractional blood volume; and influx according to Patlak. The mean SUV was 4.6 before therapy and 2.8 after 2 cycles. The mean influx was 0.059 before therapy and 0.043 after 2 cycles. The mean SUV was 3.9 in the responders and 5.5 in the nonresponders before therapy. After therapy, responders revealed a mean SUV of 2.5, whereas nonresponders had a mean SUV of 3.5. We used linear discriminant analysis to categorize the patients into 2 groups: response (n = 12) and nonresponse (n = 13). The correct classification rate of the responders (positive predictive value) was generally higher (>67%) than that for the nonresponders. Finally, the combined use of the 2 predictor variables, namely SUV and influx, of each study led to the highest accuracy of 83%. This combination was particularly useful for the prediction of responders (positive predictive value, 92%). The use of the percentage change in maximum SUV led to an accuracy of 58%. On the basis of these results, only a multiparameter analysis based on kinetic (18)F-FDG data of a baseline study and after 2 cycles is helpful for the early prediction of chemosensitivity in patients with soft-tissue sarcomas receiving neoadjuvant chemotherapy.

The higher the decrease in the standardized uptake value of positron emission tomography after chemoradiation, the better the survival of patients with gastroesophageal adenocarcinoma

Postchemoradiation percentage decrease in standardized uptake value (SUV) of positron emission tomography (PET) from baseline correlates with overall survival (OS) and pathologic response. Analyses of dichotomized data are commonly reported. The authors analyzed percentage SUV decrease as both dichotomized and continuous variables. The authors assessed 151 consecutive patients with gastroesophageal adenocarcinoma who had chemoradiation and surgery. Baseline and postchemoradiation PET/computed tomography imaging was performed. The log-rank test and Cox proportional hazards models were used to associate percentage SUV changes and OS, and logistic regression models were used to detect the association between percentage SUV changes and pathologic response. A >52% SUV decrease (dichotomized analysis) was associated with a longer OS (log-rank test, P = .023). The univariate Cox proportional hazards model indicated that greater percentage SUV decrease (as a continuous variable) was associated with a lower risk of death (hazard ratio [HR], 0.99; P = .01). Pathologic response (< or =50% residual cancer) was associated with longer OS (P = .003). Patients with chemoradiation resistance (>50% residual cancer) tended to have a higher risk of death than those with chemoradiation sensitivity (0-50% residual cancer; HR, 2.12; P = .099). In the multivariate model, the percentage SUV decrease (as a continuous variable) was the only prognosticator of OS (P = .01). The percentage SUV decrease was nonsignificantly associated with pathologic complete response (univariate odds ratio [OR], 1.01; P = .06 and multivariate OR, 1.03; P = .07). The greater the decline in SUV after chemoradiation, the longer is the OS of gastroesophageal adenocarcinoma patients. The percentage SUV decrease as a continuous variable is a better prognosticator of OS than its dichotomized assessments.

Assessment of Interobserver Reproducibility in Quantitative 18F-FDG PET and CT Measurements of Tumor Response to Therapy

Our goal was to estimate and compare across different readers the reproducibility of the (18)F-FDG PET standardized uptake value (SUV) and CT size measurements, and changes in those measurements, in malignant tumors before and after therapy. Fifty-two tumors in 25 patients were evaluated on (18)F-FDG PET/CT scans. Maximum SUVs (SUV(bw) max) and CT size measurements were determined for each tumor independently on pre- and posttreatment scans by 8 different readers (4 PET, 4 CT) using routine nonautomated clinical methods. Percentage changes in SUV(bw) max and CT size between pre- and posttreatment scans were calculated. Interobserver reproducibility of SUV(bw) max, CT size, and changes in these values were described by intraclass correlation coefficients (ICCs) and estimates of variance. The ICC was higher for the pretreatment, posttreatment, and percentage change in SUV(bw) max than the ICC for the longest CT size and the 2-dimensional CT size (before treatment, 0.93, 0.72, and 0.61, respectively; after treatment, 0.91, 0.85, and 0.45, respectively; and percentage change, 0.94, 0.70, and 0.33, respectively). The variability of SUV(bw) max was significantly lower than the variability of the longest CT size and the 2-dimensional CT size (mean +/- SD before treatment, 6.3% +/- 14.2%, 16.2% +/- 17.8%, and 27.5% +/- 26.7%, respectively, P < or = 0.001; and after treatment, 18.4% +/- 26.8%, 35.1% +/- 47.5%, and 50.9% +/- 51.4%, respectively, P < or = 0.02). The variability of percentage change in SUV(bw) max (16.7% +/- 36.2%) was significantly lower than that for percentage change in the longest CT size (156.3% +/- 157.3%, P < or = 0.0001) and the 2-dimensional CT size (178.4% +/- 546.5%, P < 0.0001). The interobserver reproducibility of SUV(bw) max for both untreated and treated tumors and percentage change in SUV(bw) max are substantially higher than measurements of CT size and percentage change in CT size. Measurements of tumor metabolism by PET should be included in trials to assess response to therapy. Although PET reproducibility was high, the variability observed in analyses of identical image sets by 4 readers indicates that automated analytic tools to assess response might be helpful to further enhance reproducibility.

Prediction Model of Chemotherapy Response in Osteosarcoma by 18F-FDG PET and MRI

Response to neoadjuvant chemotherapy is a significant prognostic factor for osteosarcoma; however, this information can be determined only after surgical resection. If we could predict histologic response before surgery, it might be helpful for the planning of surgeries and tailoring of treatment. We evaluated the usefulness of (18)F-FDG PET for this purpose. A total of 70 consecutive patients with a high-grade osteosarcoma treated at our institute were prospectively enrolled. All patients underwent (18)F-FDG PET and MRI before and after neoadjuvant chemotherapy. We analyzed the predictive values of 5 parameters, namely, maximum standardized uptake values (SUVs), before and after (SUV2) chemotherapy, SUV change ratio, tumor volume change ratio, and metabolic volume change ratio (MVCR) in terms of their abilities to discriminate responders from nonresponders. Patients with an SUV2 of less than or equal to 2 showed a good histologic response, and patients with an SUV2 of greater than 5 showed a poor histologic response. The histologic response of a patient with an intermediate SUV2 (2 < SUV2 </= 5) was found to be predictable using MVCR. A patient with an MVCR of less than 0.65 is likely to be a good responder, whereas a patient with an MVCR of greater than or equal to 0.65 is likely to be a poor responder. According to our model, the predictive values for good responders and poor responders were 97% (31/32) and 95% (36/38), respectively. We found that combined information on (18)F-FDG PET and MRI scans, acquired before and after chemotherapy, could be used to predict histologic response to neoadjuvant chemotherapy in osteosarcoma.