Range Of Standardized Uptake Value Research Articles

Combined visual and quantitative assessment of somatostatin receptor scintigraphy for staging and restaging of neuroendocrine tumors.

Somatostatin receptor scintigraphy (SRS) using 111In-DTPA-DPhe1-octreotide (pentetreotide) has become an integral part of neuroendocrine neoplasm management. The lack of precise quantification is a disadvantage of SRS. This study aimed to adapt the standardized uptake value (SUV) to SRS, establish the SUV range for physiological uptake in the liver, kidney, and spleen, and elucidate the utility of combined visual and quantitative SRS assessment for staging and restaging of neuroendocrine tumors (NETs). This study included 21 patients with NETs who underwent 111In-pentetreotide SRS. The SUV of physiological and pathological uptake was calculated using bone single-photon emission computed tomography (SPECT) quantitative analysis software (GI-BONE). For visual analysis, the primary and metastatic lesions were scored visually on planar and SPECT images using a five-point scale. We assessed the relationships between the SUVs of the liver, kidney, and spleen in the dual phase, and among quantitative indices, visual score, and pathological lesions classification. Sixty-three NEN lesions were evaluated. The mean ± standard deviation maximum SUVs (SUVmax) were liver: 4h, 2.6 ± 1.0; 24h, 2.2 ± 1.0; kidney: 4h, 8.9 ± 1.8; 24h, 7.0 ± 2.0; and spleen; 4h, 11.3 ± 4.5; 24h, 11.5 ± 7.6. Higher SUVmax was significantly associated with higher visual scores on dual-phase SPECT (4h, p < 0.001; 24h, p < 0.001) (4h: scores 3 and 4, p < 0.05; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01; 24h: scores 3 and 4, p = 0.0748; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01). We adapted the SUV to SRS and established the range of SUV for physiological uptake in the liver, kidney, and spleen. Combined visual and quantitative assessment is useful for imaging individual lesions in greater detail, and may serve as a new tumor marker of SRS for staging and restaging of NETs.

Quantitative assessment of 99mTc-methylene diphosphonate bone SPECT/CT for assessing bone metastatic burden and its prognostic value in patients with castration-resistant prostate cancers: initial results in a single-center retrospective study

To evaluate the prognostic value of the quantitative assessment of 99mTc-methylene diphosphonate (99mTc-MDP) bone SPECT/CT in castration-resistant prostate cancer (CRPC) patients with bone metastases. A total of 103 patients who underwent 99mTc-MDP bone SPECT/CT imaging from the neck to the proximal femur were included. First, in 65 patients without bone metastases, the normal range of standardized uptake value (SUV) of non-pathological bone was evaluated to determine an SUV threshold to reliably exclude most normal osseous activity. Then, in 38 CRPC patients with bone metastases, lesion uptake volume (LUV), which is the extracted volume of bone metastases exhibiting high accumulation above the SUV threshold, was calculated. The relation between LUV and prostate-related mortality was statistically evaluated. Based on the SUV measurements of non-pathological bones, the optimal SUV threshold, which defines abnormal bone SPECT uptake, was determined to be 8. Median LUV was 39mL (interquartile range 4.0-104.3mL) in the CRPC subjects with bone metastases. Kaplan-Meier survival analysis showed a significant relation between prostate cancer-specific survival and LUV (cut-off value, 19.95mL; P = 0.001). Multivariate analysis revealed LUV as an independent prognostic factor for the survival (P = 0.008, hazard ratio 23.424). Global chi-square test showed that LUV had significant incremental prognostic value in addition to prostate-specific antigen and the interval from progression to CRPC until bone SPECT/CT (P = 0.022). Quantitative assessment of 99mTc-MDP bone SPECT images can provide valuable prognostic information in CRPC patients with bone metastases.

Normal FDG uptake in the adenoids and palatine tonsils in children on PET/MRI.

Information about the normal [F-18]2-fluoro-2-deoxyglucose (FDG) uptake in the adenoids and palatine tonsils in children is not available. The purpose of this study was to report the range of standardized uptake values (SUVs) in the normal adenoids and palatine tonsils in children, assess for the degree of asymmetry between the right and left tonsils and evaluate for the correlation of SUVs between the adenoids and tonsils. Pediatric patients who had had an FDG positron emission tomography (PET)/magnetic resonance imaging (MRI) brain study in our institution from January 2018 to March 2019 were identified. Patients with a history of malignancy, adenoidectomy and/or tonsillectomy, incomplete imaging coverage of Waldeyer ring and the presence of artifact on PET/MRI were excluded. Two pediatric radiologists independently measured the mean and maximum SUVs of the right tonsil, left tonsil and the adenoids. Range, mean and standard deviation were calculated for all measurements. Ratios of SUV of the left to right tonsils and the adenoids to the tonsils were calculated. The paired t-test and Pearson's correlation test were used for statistical analysis with a P-value <0.05 considered to be significant. Sixty-one PET/MRI brain scans were performed in our institution during the study period. After reviewing for exclusion criteria, 41 patients were included in the study (mean age: 10.1years, range: 2-17years; 19 boys and 22 girls). The mean SUV was 5.30±1.57 in the right tonsil, 5.25±1.53 in the left tonsil and 4.56±1.90 in the adenoids. The maximum SUV was 8.47±2.22 in the right tonsil, 8.45±2.18 in the left tonsil and 7.59±2.94 in the adenoids. The difference between the SUVs of the right and left tonsil was not statistically significant (P=0.69 for mean SUV and P=0.90 for maximum SUV). There was a statistically significant moderately positive correlation between the FDG uptake in the adenoids and the right and left tonsil for both mean and maximum SUV (r=0.36-0.41; P=0.008-0.022). There is a wide variation of FDG uptake in the normal tonsils and adenoids in children. Uptake in the right and left tonsils is not significantly different. There is a moderately positive correlation between the FDG uptake in the adenoids and the tonsils.

Analysis of quantitative [I-123] mIBG SPECT/CT in a phantom and in patients with neuroblastoma

PurposeTo determine the accuracy of quantitative SPECT, intersystem and interpatient standardized uptake value (SUV) calculation consistency for a manufacturer-independent quantitative SPECT/CT reconstruction algorithm, and the range of SUVs of normal and neoplastic tissue.MethodsA NEMA body phantom with 6 spheres (ranging 10–37 mm) was filled with a known activity-to-volume ratio and used to determine the contrast recovery coefficient (CRC) for each visible sphere, and the measured SUV accuracy of those spheres and background water solution. One hundred eleven 123I-metaiodobenzylguanidine ([I-123] mIBG) SPECT/CT examinations from 43 patients were reconstructed using SUV SPECT® (HERMES Medical Solutions Inc.); 42 examinations were acquired using a GE Infinia Hawkeye 4 SPECT/CT, and 69 were acquired on a Siemens Symbia Intevo SPECT/CT. Inter scanner SUV analysis of 9 regions of normal [I-123] mIBG tissue uptake was conducted. Intrapatient mean SUV variability was calculated by measuring normal liver uptake within patients scanned on both cameras. The intensity of uptake by neoplastic tissue in the images was quantified using maximum SUV and, if present, compared over time.ResultsThe phantom results of the visible spheres and background resulted in accuracy calculations better than 5–10% with CRC correction. Interscanner SUV variability showed no statistical difference (average p value 0.559; range 0.066–1.0) among the 9 normal tissues analyzed. Intrapatient liver mean SUV varied ≤ 16% as calculated for 28 patients (87 examinations) studied on both scanners. In one patient, a thoracic tumor evaluated over 10 time points (18 months) underwent a 74% (3.1/12.0) reduction in maximum SUV with treatment.ConclusionThe results demonstrate quantitative accuracy to better than 10%, and both consistent SUV calculation between 2 different SPECT/CT scanners for 9 tissues, and low intrapatient measurement variability for quantitative SPECT/CT analysis in a pediatric population with neuroblastoma. Quantitative SPECT/CT offers the opportunity for objective analysis of tumor response using [I-123] mIBG by normalizing the uptake to injected dose and patient weight, as is done for PET.

A study of PET-CT SUV range for dose verification in carbon ion radiation therapy

Objective The positron generated at the dose deposition site by using high-energy carbon ions to hit the material annihilate with the negative electron in the material to release the gamma photon. The positron-emitting isotope (PEI) distributions in the target volume are activated significantly by carbon ions. Therefore, the mean values of positron emission tomography (PET) activity could be related to the delivered doses to the clinical target volume from carbon ion. This specialty can be used for the image registration fusion of the carbon ion treatment planning computed tomography (CT) and treatment verification PET-CT. After radiation in the almost same decay period, the relationship between the different target volume and the PET-CT SUV of different every single fraction dose can be found, then the range of SUV for the radiation target could be decided. So this PET-CT standardized uptake value (SUV) range can also provide a reference for the correlation and consistency in planning target dose verification and evaluation for the clinical trial. Methods The head phantom was used as a simulation of the real human body, the 1 cc, 4 cc, and 10 cc cube volume target contouring were done in the TPS, the 90 degree fixed carbon ion beams were delivered in different single fraction effective dose of 2.5 GyE, 5 GyE, and 8 GyE. After the beam delivery, later the PET-CT scanning was performed and parameters of scanning followed the trial regulation. The MIM Maestro software was used for the image processing and fusion to determine the maximum, minimum, average, and total values of SUV in the virtual clinical target volumes for the different single fraction dose. Results The results showed that for the same target volume, the SUV range of target had an approximate linear correlation with effective dose of target (P=0.000). The same effective dose for the different target volumes got the same SUV range (P>0.05). Conclusions For the carbon ion treatment plan, the SUV range from image registration and fusion of planning CT and PET-CT after treatment can be used to make an evaluation for accuracy of the dose distribution. And this method also could be used in the hyper-fraction treatment plan. In the SUV range research of different decay periods, the similar method can be performed for the exploration. Key words: Carbon ion therapy; Dose verification; Tomography, positron emission; Tomography, X-ray computed

Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging.

Ga-PSMA-11 is a novel PET tracer suggested to be used for imaging of advanced prostate cancer. In this study, we aimed to present a detailed biodistribution of Ga-PSMA-11, including physiological and benign variants of prostate-specific membrane antigen (PSMA) imaging. We carried out a retrospective analysis of 40 patients who underwent PSMA PET/computed tomography (CT) imaging and who had no evidence of residual or metastatic disease on the scans. In addition, 16 patients who underwent PSMA PET/CT imaging with any indication other than prostate cancer were included in the study to evaluate physiological uptake in the normal prostate gland. The median, minimum-maximum, and mean standardized uptake value (SUV) values were calculated for visceral organs, bone marrow and lymph nodes, and mucosal areas. Any physiological variants or benign lesions with Ga-PSMA-11 were also noted. Ga-PSMA-11 uptake was noted in the kidneys, parotid and submandibular glands, duodenum, small intestines, spleen, liver, and lacrimal glands, and mucosal uptake in the nasopharynx, vocal cords, pancreas, stomach, mediastinal blood pool, thyroid gland, adrenal gland, rectum, vertebral bone marrow, and testes. Celiac ganglia showed slight Ga-PSMA-11 uptake in 24 of 40 patients without the presence of any other pathologic lymph nodes in abdominal and pelvic areas. Variable uptake of Ga-PSMA-11 was observed in calcified choroid plexus, a thyroid nodule, an adrenal nodule, axillary lymph nodes and celiac ganglia, occasional osteophytes, and gallbladder. The patient group with PSMA PET/CT for indications other than prostate cancer (n=16) showed a slight radiotracer uptake in normal prostate gland (SUVmax: 5.5±1.6, range: 3.5-8.3). This study shows normal distribution pattern, range of SUVs, and physiological variants of Ga-PSMA-11. In addition, several potential pitfalls were documented to prevent misinterpretations of the scan.

Quantitative Analysis of Torso FDG-PET Scans by Using Anatomical Standardization of Normal Cases from Thorough Physical Examinations.

Understanding of standardized uptake value (SUV) of 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) depends on the background accumulations of glucose because the SUV often varies the status of patients. The purpose of this study was to develop a new method for quantitative analysis of SUV of FDG-PET scan images. The method included an anatomical standardization and a statistical comparison with normal cases by using Z-score that are often used in SPM or 3D-SSP approach for brain function analysis. Our scheme consisted of two approaches, which included the construction of a normal model and the determination of the SUV scores as Z-score index for measuring the abnormality of an FDG-PET scan image. To construct the normal torso model, all of the normal images were registered into one shape, which indicated the normal range of SUV at all voxels. The image deformation process consisted of a whole body rigid registration of shoulder to bladder region and liver registration and a non-linear registration of body surface by using the thin-plate spline technique. In order to validate usefulness of our method, we segment suspicious regions on FDG-PET images manually, and obtained the Z-scores of the regions based on the corresponding voxels that stores the mean and the standard deviations from the normal model. We collected 243 (143 males and 100 females) normal cases to construct the normal model. We also extracted 432 abnormal spots from 63 abnormal cases (73 cancer lesions) to validate the Z-scores. The Z-scores of 417 out of 432 abnormal spots were higher than 2.0, which statistically indicated the severity of the spots. In conclusions, the Z-scores obtained by our computerized scheme with anatomical standardization of torso region would be useful for visualization and detection of subtle lesions on FDG-PET scan images even when the SUV may not clearly show an abnormality.

Standardized uptake value differences between primary and metastatic lesions in ¹⁸F-FDG PET/CT of patients with lung cancer.

FDG-PET/CT is a robust tool for staging of lung cancer, but the differences in FDG uptake between primary and metastatic lesions have not yet been well described. To define the potential range of standardized uptake value (SUV) differences between primary and metastatic lesions in lung cancer patients and to identify the factors responsible for these differences. FDG-PET/CT images of 75 lung cancers with 296 metastases were analyzed retrospectively. Histological types, primary locations, and metastatic sites were recorded. The average and maximum SUV (SUVavg, SUVmax) of each primary tumor and metastasis were measured, and the ratio of metastatic SUVs to primary SUVs (M/Pavg, M/Pmax), its difference from 100% (diff-M/Pavg, diff-M/Pmax), the ratio of ROI area of metastatic to primary lesions (ROI-M/P), and its difference from 100% (diff-ROI-M/P) were calculated. M/Pavg was in the range of 35.9-224.6% (mean ± SD: 97.9% ± 35.9%), while M/Pmax was in the range of 24.8-286.7% (98.1% ± 45.3%). Furthermore, values were in the range of 50-200% for M/Pavg in 280/296 lesions (94.6%) and for M/Pmax in 255/296 lesions (86.1%). M/Pavg and M/Pmax showed significant linear correlations with ROI-M/P (r = 0.62, 0.64, respectively). Multivariate analysis showed that diff-ROI-M/P had the greatest effect on diff-M/Pavg and diff-M/Pmax. The SUVs of most metastatic lesions ranged from half to double those of primaries in lung cancer patients. When the SUV of a suspected metastasis is beyond the range of half to double that of the primary lung cancer, other non-metastatic lesions should be considered, while taking ROI size into account.

PET Imaging of Estrogen Receptors as a Diagnostic Tool for Breast Cancer Patients Presenting with a Clinical Dilemma

16α-(18)F-fluoro-17β-estradiol ((18)F-FES) is an estrogen receptor (ER)-specific PET tracer with various potential interesting applications. The precise contribution of this technique in current clinical practice, however, has yet to be determined. Therefore, the aim of this study was to evaluate the value of (18)F-FES PET in breast cancer patients presenting with a clinical dilemma. (18)F-FES PET examination could be requested by referring physicians for patients with a history of ER-positive breast cancer and the presence of a clinical dilemma despite complete standard work-up. All requests for (18)F-FES PET required a positive arbitration by a dedicated medical oncologist and nuclear medicine physician. The referring physician was asked to fill in validated questionnaires before, shortly after, and at more than 3 mo after (18)F-FES PET to determine indication, diagnostic value, and therapeutic consequences of (18)F-FES PET. To further validate (18)F-FES PET findings, (18)F-FES PET lesions were quantified and compared with centrally reviewed conventional imaging. Thirty-three patients underwent (18)F-FES PET between December 2008 and October 2010. (18)F-FES PET was requested to evaluate equivocal lesions on conventional work-up (n = 21), ER status in metastatic patients (n = 10), and the origin of metastases (n = 2). (18)F-FES-positive lesions were observed in 22 patients. (18)F-FES PET was especially sensitive for bone metastases, detecting 341 bone lesions, compared with 246 by conventional imaging. The sensitivity for liver metastases was poor, and quantification of (18)F-FES uptake in liver lesions was hampered by high physiologic background. (18)F-FES uptake was highly variable between all metastases (range of standardized uptake value, 1.20-18.81), and 45% of the patients with a positive (18)F-FES PET finding had both (18)F-FES-positive and (18)F-FES-negative metastases. (18)F-FES PET improved diagnostic understanding in 88% of the patients and led to therapy change in 48% of the patients. With the exception of liver metastases, whole-body imaging of ER expression with (18)F-FES PET can be a valuable additional diagnostic tool when standard work-up is inconclusive. (18)F-FES PET supported therapy decisions by improving diagnostic understanding and providing information on ER status of tumor lesions.

SU‐C‐110‐03: Utility of Maximum Intensity Projections of Gated PET Images in Determining Internal Target Volumes of Moving Lung Tumors: A Phantom Study

Purpose: To examine maximum intensity projections (MIPs) as a method for segmenting lung tumor internal target volumes (ITVs) in positron emission tomography (PET) images using two threshold‐based methods, and to assess various parameters that potentially affect the accuracy of tumor segmentation by this technique. Methods and Materials: An acrylic phantom setup, consisting of a 1.5cm diameter sphere filled with 11 ‐C solution inside a cylindrical bath of 18‐fluorodeoxyglucose solution, was used for a PET list‐mode acquisition. The phantom was attached to a robotic arm that moved according to four patient breathing trajectories via an abdominal breathing bellows device. List‐mode data was gated based on the breathing trajectories, and PET‐MIPs were created from the reconstructed gated images. ITVs were calculated and compared for both un‐gated PET images and PET‐MIPs by using varying thresholds of absolute standardized uptake value (SUV) and percentage of maximum SUV. In addition, a simulation of PET‐MIPs was performed to examine the effects of tumor size, image smoothing, and tumor trajectory on the accuracy of ITV measurement. Results: For any given threshold value, PET‐MIPs tended to produce larger ITVs than un‐gated PET. For optimal percentage thresholds across all trajectories, PET‐MIPs measured an ITV to within 5% accuracy in a larger SUV range with lower initial values than un‐gated PET for the same accuracy. For both PET‐MIP and un‐gated PET, a percentage threshold method produced a smaller deviation from true ITV in similar SUV ranges when compared to an absolute threshold method. The PET‐MIP simulation demonstrated greater accuracy of ITV measurement with increased image smoothing and sphere size. Breathing trajectories exhibiting baseline drift negatively impacted accurate ITV determination. Conclusion: Threshold‐based ITV segmentation is sensitive to lung tumor volume, trajectory, and SUV. PET‐MIPs appear to be a promising tool in the accurate delineation of lung tumor ITV.

Distribution pattern of 68Ga-DOTATATE in disease-free patients

68Ga-DOTA-DPhe1,Tyr3-octreotate (68Ga-DOTATATE) is a somatostatin analogue that shows high affinity for somatostatin receptor subtype 2 (sst2) and has been used for imaging neuroendocrine tumours. However, normal uptake patterns and potential pitfalls have not been described with this high-sensitivity radiotracer. The aim of this study was therefore to outline the normal distribution pattern of 68Ga-DOTATATE in disease-free patients, to provide standardized uptake values (SUVs) of various organs and to compare our results with the current knowledge on sst2 receptor expression in vitro. 68Ga-DOTATATE PET/computed tomography was performed in 42 patients (15 men and 27 women). Approximately 145 MBq of tracer was injected intravenously and imaging was performed using a GE Discovery ST PET/computed tomography scanner. SUVs were calculated on the reconstructed images for various organs. 68Ga-DOTATATE uptake was noted in the sst2-expressing organs such as pituitary, thyroid, stomach wall, spleen, adrenals, kidneys, pancreas and prostate and in the liver and salivary glands, with excreted activity in the bowel and in the pelvicalyceal system of the kidneys and urinary bladder. The SUVs ranged from 0.1 to 48.8 in the organs considered. Potential pitfalls in interpreting the 68Ga-DOTATATE uptake in organs such as thyroid, pancreas lymph nodes and bowel were identified. This study shows the distribution pattern of 68Ga-DOTATATE outlines the range of SUVs for various organs in disease-free patients and identifies some of the potential pitfalls encountered during imaging.

An update on the usefulness of the intensity of 18fluorodeoxyglucose uptake in positron emission tomography (FDG-PET) in distinguishing between indolent and aggressive non-Hodgkin’s lymphomas

8602 Background: FDG PET is recommended for the initial evaluation and staging of patients with non-Hodgkin’s lymphoma (NHL). There is not enough knowledge about the usefulness of PET in distinguishing different subtypes of NHL, so we investigated whether the intensity of tumor FDG uptake in NHL is different between indolent and aggressive histology. This comparison may also clarify the value ot an initial PET scan in indolent lymphoma, because of its lower and unpredictable uptake. Methods: We studied a retrospective cohort of lymphoma patients with NHL, attended at a single tertiary care center from April 2003 to November 2007 and who had not received treatment. We reviewed the initial, re-staging and/or relapse PET studies of 101 patients with diagnosis of NHL. Mean age 45 (15 to 86) years, 41 female and 60 male. We recorded the highest standardized uptake value (SUV), correlations were made with histopathology. We analyzed SUVs considering the various histologies and grades. Two sample comparisons were performed using the Wilcoxon test. Results: The histopathological diagnoses were: diffuse large B-cell lymphomas (53 patients), anaplastic large cell lymphoma (8 patients), Follicular lymphoma grade 1 and 2 (25 patients), Follicular lymphoma grade 3 (5), Burkitt (5), and other types (5 patients, 1 MALT, 1 lymphoma/CLL, 1 mycosis fungoides, 2 peripheral t cell lymphoma). FDG uptake was lower in indolent (29 patients) than aggressive lymphoma (72 patients) (SUV, mean 5.8, SD ± 2.2, mean rank 26.2, sum of ranks 768 vs 13.5 SD ± 6.9, mean rank 60.9, sum of ranks 4388; P=<.0001). Despite overlap between indolent and aggressive disease in the low SUV range (indolent 1.9 to 11; aggressive 3.2 to 33) all cases of indolent lymphoma had an SUV ≤ 11. Conclusions: These findings confirm our previous results showing that the FDG uptake is significantly lower in indolent than in aggressive lymphoma. Patients with NHL and SUV > 11 have a high likelihood for aggressive disease. These results also suggest that to follow the treatment response in indolent lymphoma is important to have an initial PET study. No significant financial relationships to disclose.

The usefulness of the intensity of 18fluorodeoxyglucose uptake in positron emission tomography (FDG-PET) in distinguishing between indolent and aggressive non-Hodgkin's lymphomas

6584 Purpose: FDG PET is recommended for the initial evaluation and staging of patients with non-Hodgkin's lymphoma (NHL). We investigated whether the intensity of tumor FDG uptake in NHL is significantly different between indolent and aggressive histology. Materials and Methods: We studied a retrospective cohort of lymphoma patients with NHL, attended at a single tertiary care center from April 2003 to November 2006 and who had not received treatment. We reviewed the initial, re-staging and/or relapse PET studies of 50 patients with diagnosis of NHL. Mean age 42 (15 to 72) years, 27 female and 23 male. We recorded the highest standardized uptake value (SUV), correlations were made with histopathology. We analyzed SUVs considering the various histologies and grades. Two sample comparisons were performed using the Wilcoxon test. Results: The histopathological diagnoses were: diffuse large B-cell lymphomas (26 patients), anaplastic large cell lymphoma (7 patients), Follicular lymphoma (14 patients), and other types (3 patients, 1 MALT, 1 Burkitt and 1 small cell Burkitt-like). FDG uptake was lower in indolent (15 patients) than aggressive lymphoma (35 patients) (SUV, mean 6.2, SD  ± 1.7, mean rank 15.47, sum of ranks 232 vs 12.9  ± 7.4, mean rank 29.8, sum of ranks 1,043; P=.001). Despite overlap between indolent and aggressive disease in the low SUV range (indolent 3.7 to 9.3; aggressive 3.2 to 24.9) all cases of indolent lymphoma had an SUV ≤ 9.3. Conclusion: FDG uptake is significantly lower in indolent than in aggressive lymphoma. Patients with NHL and SUV &gt; 10 have a high likelihood for aggressive disease. As with other retrospective studies, this information should be confirmed prospectively, but this data allows formulating new hypothesis about correlations between the SUV, the molecular subtypes and the clinical behaviour of the lymphomas No significant financial relationships to disclose.

Role of Positron Emission Tomography in Lymphoma

Positron emission tomography (PET) scanning, particularly using [F]fluorodeoxyglucose (FDG), has recently emerged as a powerful functional imaging tool for assessment of patients with Hodgkin’s disease and nonHodgkin’s lymphoma (NHL). Numerous investigations have been reported on its use for staging, restaging, and monitoring tumor response of lymphoma, with only a few exploring its value in predicting the tumor’s malignancy grade. In this issue of the Journal of Clinical Oncology, Schoder et al seek to determine whether the intensity of FDG uptake measured using the standardized uptake value (SUV) could differentiate between indolent and aggressive NHL. The SUV is a semiquantitative measure of the degree of FDG uptake, which may be conceptualized as the ratio between the tumoral concentration of tracer and its concentration in the entire body if the tracer were evenly distributed throughout. Because of its simplicity, this parameter is widely utilized both in the research setting and in clinical practice. In their study of 97 patients with NHL, Schoder et al concluded that the SUV is lower in indolent than in aggressive NHL, that patients with an SUV 10 have a high likelihood of aggressive NHL, and that this information may be helpful if there is discordance between biopsy and clinical behavior. These findings clearly have implications in treatment planning and prognosis. While the study by Schoder et al is the largest to date to attempt to distinguish between indolent and aggressive NHLs based on the SUV, the findings are not very different from those of previously reported smaller studies. Similar to those previous studies, a considerable overlap in the SUVs was found between indolent and aggressive NHL, with a relatively wide range of SUVs observed even within the same histologic subtype. This variability could have been even greater had the authors determined the SUVs for all well-delineated tumor lesions in each patient rather than only for the most intense lesion because of the known intrapatient variability in SUV in patients with NHL and other cancer types. Despite this overlap, two conclusions may be drawn reasonably from the data. First, an SUV 13 in the most intense lesion indicates a high likelihood of aggressive histology, while an SUV of 6 is very likely associated with indolent histology. Second, these upper and lower cutoff SUVs provide relatively high accuracy in grading NHL in only approximately 55% of patients, because only approximately 58% of patients with biopsy-proven aggressive histology had an SUV 13, and slightly less than 50% of those with indolent histology had an SUV 6. Consequently, approximately 45% of patients remain in a gray zone between the SUVs of 6 and 13, where the overlap is so pronounced that it practically precludes a justifiable degree of confidence in grading NHL. The adverse effect of this overlap becomes apparent when examining the results of the receiver operating characteristic (ROC) analysis used to determine optimum cutoff SUV that distinguishes indolent from aggressive histologies: this optimum cutoff SUV of 10, although associated with a fair balance of sensitivity and specificity, resulted in a 29% misclassification rate for aggressive NHL and a 19% misclassification rate for indolent NHL. The latter may result in overtreatment of a significant fraction of patients with indolent lymphoma. Conversely, misclassification of almost one third of patients with aggressive lymphoma may result in their undertreatment, which cannot be justified considering the potentially curable nature of their disease. The moderate sensitivity and specificity of the cutoff SUV of 10 needs to be further evaluated in light of the fact that this value was derived post hoc, potentially resulting in an overestimation of its diagnostic accuracy. However, the findings in the 22 patients in whom the biopsy was taken from a site other than that with the most intense FDG uptake could serve as an initial test for the performance of this cutoff in an independent, albeit small, cohort of JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 21 JULY 2

Intensity of18Fluorodeoxyglucose Uptake in Positron Emission Tomography Distinguishes Between Indolent and Aggressive Non-Hodgkin’s Lymphoma

(18)Fluorodeoxyglucose positron emission tomography (FDG PET) is widely used for the staging of lymphoma. We investigated whether the intensity of tumor FDG uptake could differentiate between indolent and aggressive disease. PET studies of 97 patients with non-Hodgkin's lymphoma who were untreated or had relapsed and/or persistent disease and had not received treatment within the last 6 months were analyzed, and the highest standardized uptake value (SUV) per study was recorded. Correlations were made with histopathology. FDG uptake was lower in indolent than in aggressive lymphoma for patients with new (SUV, 7.0 +/- 3.1 v 19.6 +/- 9.3; P < .01) and relapsed (SUV, 6.3 +/- 2.7 v 18.1 +/- 10.9; P = .04) disease. Despite overlap between indolent and aggressive disease in the low SUV range (indolent, 2.3 to 13.0; aggressive, 3.2 to 43.0), all cases of indolent lymphoma had an SUV <or= 13. A receiver operating characteristic (ROC) analysis demonstrated that the SUV distinguished reasonably well between aggressive and indolent disease (area under ROC curve, 84.7%), and an SUV > 10 excluded indolent lymphoma with a specificity of 81%. With a higher cutoff for the SUV, the specificity would have been higher. FDG uptake is lower in indolent than in aggressive lymphoma. Patients with NHL and SUV > 10 have a high likelihood for aggressive disease. This information may be helpful if there is discordance between biopsy and clinical behavior.