SUV Measurements Research Articles

Clinical Evaluation of a Data-Driven Respiratory Gating Algorithm for Whole-Body PET with Continuous Bed Motion

Respiratory gating is the standard to prevent respiration effects from degrading image quality in PET. Data-driven gating (DDG) using signals derived from PET raw data is a promising alternative to gating approaches requiring additional hardware (e.g., pressure-sensitive belt gating [BG]). However, continuous-bed-motion (CBM) scans require dedicated DDG approaches for axially extended PET, compared with DDG for conventional step-and-shoot scans. In this study, a CBM-capable DDG algorithm was investigated in a clinical cohort and compared with BG using optimally gated (OG) and fully motion-corrected (elastic motion correction [EMOCO]) reconstructions. Methods: Fifty-six patients with suspected malignancies in the thorax or abdomen underwent whole-body 18F-FDG CBM PET/CT using DDG and BG. Correlation analyses were performed on both gating signals. Besides static reconstructions, OG and EMOCO reconstructions were used for BG and DDG. The metabolic volume, SUVmax, and SUVmean of lesions were compared among the reconstructions. Additionally, the quality of lesion delineation in the different PET reconstructions was independently evaluated by 3 experts. Results: The global correlation coefficient between BG and DDG signals was 0.48 ± 0.11, peaking at 0.89 ± 0.07 when scanning the kidney and liver region. In total, 196 lesions were analyzed. SUV measurements were significantly higher in BG-OG, DDG-OG, BG-EMOCO, and DDG-EMOCO than in static images (P < 0.001; median SUVmax: static, 14.3 ± 13.4; BG-EMOCO, 19.8 ± 15.7; DDG-EMOCO, 20.5 ± 15.6; BG-OG, 19.6 ± 17.1; and DDG-OG, 18.9 ± 16.6). No significant differences between BG-OG and DDG-OG or between BG-EMOCO and DDG-EMOCO were found. Visual lesion delineation was significantly better in BG-EMOCO and DDG-EMOCO than in static reconstructions (P < 0.001); no significant difference was found when comparing BG and DDG for either EMOCO or OG reconstruction. Conclusion: DDG-based motion compensation of CBM PET acquisitions outperforms static reconstructions, delivering qualities comparable to BG approaches. The new algorithm may be a valuable alternative for CBM PET systems.

Initial experience with a PET/computed tomography system using silicon photomultiplier detectors

A PET/computed tomography (CT) that uses silicon photomultiplier (SiPM) technology was installed at our institution. Here, we report the initial use of the new scanner and evaluate the image quality in comparison to standard PET/CT scanners. Seventy-two patients were scanned first using standard PET/CT followed immediately by the new PET/CT system. Images from the new PET/CT system were reconstructed using a conventional [non time-of-flight (TOF)] algorithm, TOF alone and TOF in combination with BSREM. Images from standard PET/CT were reconstructed using clinical standard-of-care settings. Three blinded readers randomly reviewed four datasets (standard, non-TOF, TOF alone, TOF+BSREM) per patient for image quality using a five-point Likert scale. SUV measurements for the single most avid lesion on each dataset were also recorded. Datasets from the new scanner had higher image quality (P < 0.001) and SUV measurements (P < 0.001) compared with the standard scanners, and scores further improved when TOF and BSREM algorithms were added (mean scores for standard, non-TOF, TOF alone and TOF+BSREM were 3.1, 3.9, 4.3 and 5.0, respectively; mean SUVmax for hottest lesion were 8.8, 10.3, 10.7 and 13.3, respectively). The SiPM-based PET/CT system outperforms two standard Bismuth germanium oxide- and Lutetium-yttrium oxyorthosilicate-based scanners in terms of image quality, with further benefits added using TOF and BSREM. This may be beneficial for detecting small lesions and more accurate disease staging.

Physiological 68Ga-RM2 uptake in patients with biochemically recurrent prostate cancer: an atlas of semi-quantitative measurements.

68Ga-RM2 is a bombesin (BBN) analog that targets the gastrin releasing peptide receptors (GRPR) overexpressed in many cancer cells, including prostate cancer (PC). It has been reported to successfully detect primary and recurrent PC. Here, we describe the distribution and range of physiological uptake of 68Ga-RM2 in 95 patients with biochemically recurrent (BCR) PC. Ninety-five participants had simultaneous PET/MRI for BCR PC and were prospectively enrolled in this study. Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) were measured in 24 normal anatomical structures for each participant. Three readers evaluated the images independently. Uptake in various normal tissues was classified into 4 different categories: no significant uptake if SUVmean was less than SUVmean of the aortic arch (AA); mild if SUVmean was less or equal to 2.5, but higher than SUVmean of the AA; moderate if SUVmean was higher than 2.5, but less or equal to 5; intense if SUVmean was higher than 5. The most intense uptake was observed in the urinary bladder, due to excretion of the radiotracer. No significant uptake was seen in the brain, salivary glands, lungs, myocardium, skeleton, muscles, and fat. Liver, spleen, and adrenal glands had mostly no significant uptake; the gastrointestinal tract had intense physiological uptake, with pancreas being the organ with the highest SUVmax measurements (average SUVmax 64.91). Mild and moderate uptake was measured in the esophagus (average SUVmax 3.99), while the stomach wall, duodenum, and rectum had mild uptake (average SUVmax 2.49, 3.42, and 3.58, respectively). 68Ga-RM2 has been mostly evaluated for PC detection, but it can be used for other tumors overexpressing GRPR such as breast cancer. This atlas of normal biodistribution and SUV measurements in healthy tissues will help physicians distinguish between physiological vs. pathological uptake, as well as potentially assist with planning future studies using GRPR targeting radiopharmaceuticals.

A prospective feasibility study evaluating the role of multimodality imaging and liquid biopsy for response assessment in locally advanced rectal carcinoma.

Colorectal cancer is a commonly encountered disease that poses several diagnostic and therapeutic challenges. The inherent heterogeneity of tumor biology and propensity to relapse despite "curative" resection pose significant challenges with regard to response assessment. Although MR imaging already plays a key role in primary staging of patients with rectal carcinoma, its reliability in restaging after neoadjuvant therapy is debatable (Van der broek et al. in Dis Colon Rectum 60(3):274-283, 2017). Therefore, there is significant interest in developing additional methods which may improve diagnostic accuracy. This study aims to evaluate the role of multimodality imaging and liquid biopsy in therapeutic response assessment. Seventeen patients were enrolled into the study over a span of 24months. All underwent hybrid PET-MRI and CT-perfusion (CT-P), prior to and following neoadjuvant therapy for locally advanced rectal carcinoma. Twelve of the 17 patients also underwent liquid biopsy, which consisted of blood sampling and analysis of circulating tumor cells (CTCs) and extracellular vesicles (EVs), includingcell fragments and microparticles (MPs), using the Cell Search System (Menarini Silicon Biosystems). SUV, DWI, and ADC were calculated during PET-MRI, and several parameters were evaluated during CT-perfusion, including average perfusion, blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface area product (PS), contrast extraction efficiency (E), and K-trans (K). Changes observed pre- and post-neoadjuvant therapy in each modality were compared to tumor response at histopathology using a modified Ryan tumor regression grading system. Of the 17 patients included in the study, 14 were classified as non-responders, and 3 were classified as responders as determined by the modified Ryan Tumor Regression Grade (TRG) scoring system (Van der broek et al. in Dis Colon Rectum 60(3):274-283, 2017). When combined, blood markers and CT-P parameters (mean transit time (MTT), K-trans, and permeability-surfacearea product (PS)) produced the strongest models (p < 0.01). PET (SUV measurement) combined with CT-P-derived K-trans produced a marginally significant (p = 0.057) model for predicting response. MRI-derived ADC value did not provide a significant model for response prediction. A model of CT-P parameters plus liquid biopsy more accurately predicts tumor response than PET-MRI, CT-P alone, or liquid biopsy alone. These results suggest that in the evaluation of treatment response, liquid biopsy could provide additional information to functional imaging modalities such as CT-P and should therefore be explored further in a trial with larger sample size.

Intra- and Interobserver Agreement of SUV SPECT Quantitative SPECT/CT Processing Software, Applied in Clinical Settings for Patients with Solid Renal Tumors.

Quantification tools for SPECT/CT are a field of ongoing research among hybrid imaging techniques. A recent multicenter study evaluating SUV SPECT software on phantoms showed that quantitative SPECT/CT is reproducible in Hybrid Viewer software. The aim of our study was to evaluate the intra- and interobserver agreement of quantitative SUV SPECT measurements in clinical settings for patients with solid renal tumors. Methods: The evaluation was part of a study that examined the role of 99mTc-sestamibi SPECT/CT in the characterization of solid kidney tumors and the differentiation of renal oncocytomas from renal cell carcinomas. Quantitative evaluation of SUV measurements was performed in Hybrid Viewer PDR, version 2.5. Forty-eight renal lesions were identified and examined twice by 2 independent readers. The agreement of the SUV measurements, concerning renal tumors and adjacent renal parenchyma, was evaluated using the intraclass correlation coefficient (ICC). Results: ICC for SUVmax measurements by the same reader was 97%-99% for solid renal tumors and 92%-98% for ipsilateral healthy renal parenchyma. ICC for SUVmax measurements between readers was 87%-89% for solid renal tumors and 72%-73% for ipsilateral healthy renal parenchyma. Estimated ICC for SUVmean measurements of solid renal tumors was 95%-98% for the same reader and 86%-89% between readers. Similar results were found for SUVpeak measurements. Conclusion: The high ICCs indicate a strong agreement among SUV measurements for patients with solid renal lesions undergoing 99mTc-sestamibi SPECT/CT, not only for measurements by the same reader but also for measurements between 2 different readers.

Combinative evaluation of primary tumor and lymph nodes in predicting pelvic lymphatic metastasis in early-stage cervical cancer: A multiparametric PET-CT study

PurposeThe purpose of this study is to investigate the value of combining tumor and pelvic lymph node (PLN) characteristics on PET-CT in predicting PLN metastasis of patients with early-stage cervical cancer, specifically to further reduce the false-negative cases of diagnosis. MethodsThe [18F] FDG PET-CT imaging data of 394 patients who were newly diagnosed with cervical cancer (FIGO stage, Ia-IIa) were retrospectively studied. We measured size, total lesion glycolysis (TLG) of tumor, metabolic tumor volume (MTV), maximum and mean standardized uptake value (SUVmax, SUVmean) of tumor and lymph node (LN). Diagnostic efficiency was evaluated using receiver operator characteristic (ROC) curve. We also investigated additional CT diagnosis information in PET-negative cases. ResultsOur results indicated both lymph node and tumor parameters were independent risk factors for lymphatic metastasis in early-stage cervical cancer. The diagnosis based on above meaningful parameters, we name it ‘combination diagnosis’, offered significantly higher predictive value than that based on SUV measurement alone, which the values of AUC were 0.842 and 0.784 respectively (P < 0.05). In PET-negative cases, we also found that tumor TLG, suspicious LN in lymphatic drainage pathway, long/short axis of LN ≤ 2, heterogeneity of LN significantly associated with PLN metastasis. ROC analysis showed combination diagnosis of all these parameters above produced an AUC value of 0.859 (P < 0.05, 95% CI, 0.811–0.899), which was significantly higher than either using tumor TLG alone (AUC = 0.622, Z = 3.919, P < 0.05) or indices derived from CT alone (AUC = 0.727, 0.668, 0.695. Z = 3.620, 5.356, 3.696, P < 0.05). ConclusionsWe proposed a combination diagnosis method that can better predict PLN metastasis for patients with early-stage cervical cancer. In PET-negative cases, combination diagnosis of TLG of tumor and CT indicators also produced improved prediction by reducing false-negative cases of diagnosis. This combination diagnosis approach has significant implications in cervical cancer patient management and treatment planning.

FDG PET/CT as a survival prognostic factor in patients with advanced renal cell carcinoma

Accurate prediction of the outcome of molecular target-based treatment in advanced renal cell carcinoma (RCC) is an important clinical problem. Positron emission tomography/computed tomography using [18F]-2-fluoro-2-deoxyglucose (FDG PET/CT) is a noninvasive tool for the assessment of glucose accumulation which can be a marker of the biological characteristics of the tumor. In this paper, we assess FDG PET/CT as a survival prognostic marker in patients with advanced RCC. The study included 121 patients treated in the years 2011–2016 with a diagnosis of advanced renal cell carcinoma (stage IV, multifocal metastases in all patients). Assessment using FDG PET/CT was conducted by measuring the maximum standard uptake value (SUVmax) for the marker used (the highest SUV measurement result for each patient in a single examination). SUVmax measurements were compared with various clinical risk factors used as prognostic markers. The median follow-up period was 19 months (ranging from 3 to 61 months). SUVmax measurements in all patients ranged from 1.3 to 30.0 (median 6.9). Higher SUVmax was correlated with poorer prognosis. Multi-way analysis with standard risk factors revealed that SUVmax was an independent factor for overall survival (OS; p < 0.003, hazard ratio 1.312, 95% CI 1.147–1.346). For SUVmax < 7.0, median OS was 32 months. For 7.0 ≤ SUVmax < 12.0, median OS was 12.5 months. For SUVmax ≥ 12.0, median OS was 10 months. The differences were statistically significant. A preliminary SUVmax assessment conducted using FDG PET/CT can provide information useful in the prediction of survival of patients with advanced RCC.

Palatine tonsil SUVmax on FDG PET-CT as a discriminator between benign and malignant tonsils in patients with and without head and neck squamous cell carcinoma of unknown primary

To analyse the maximum standardised uptake value (SUVmax) ratio between tonsils in patients with and without tonsillar carcinoma to determine useful diagnostic thresholds. Positron-emission tomography (PET)/computed tomography (CT) examinations of patients with suspected head and neck squamous cell carcinoma (SCC) and controls from April 2013 to September 2016 were reviewed retrospectively. Tonsillar SUVmax ratios (ipsilateral/contralateral for malignant tonsils, maximum/minimum for patients without [controls]) were calculated and used to construct a receiver operating characteristic (ROC) curve. Twenty-five patients had tonsillar carcinoma (mean SUVmax ratio of 2, range 0.89-5.4) and 86 patients acted as controls (mean SUVmax ratio of 1.1, range 1-1.5). Using the ROC, the most accurate SUVmax ratio for identifying malignancy was >1.2 (77% sensitivity, 86% specificity). A potentially more clinically useful SUVmax ratio is ≥1.6 with 62% sensitivity and 100% specificity. An SUVmax ratio between tonsils of ≥1.6 is highly suspicious for SCC and could be used to direct site of biopsy. Some malignant tonsils had normal FDG uptake; therefore, PET/CT should not be used to exclude tonsillar cancer. Minor asymmetrical uptake is frequently seen in non-malignant tonsils and does not necessarily require further investigation. Due to the single centre nature of this study and the recognised variation in SUV measurements between PET scans, other centres may need to develop their own cut-offs.

Test-Retest Reproducibility of 18F-FDG PET/CT Uptake in Cancer Patients Within a Qualified and Calibrated Local Network.

Calibration and reproducibility of quantitative 18F-FDG PET measures are essential for adopting integral 18F-FDG PET/CT biomarkers and response measures in multicenter clinical trials. We implemented a multicenter qualification process using National Institute of Standards and Technology-traceable reference sources for scanners and dose calibrators, and similar patient and imaging protocols. We then assessed SUV in patient test-retest studies. Methods: Five 18F-FDG PET/CT scanners from 4 institutions (2 in a National Cancer Institute-designated Comprehensive Cancer Center, 3 in a community-based network) were qualified for study use. Patients were scanned twice within 15 d, on the same scanner (n = 10); different but same model scanners within an institution (n = 2); or different model scanners at different institutions (n = 11). SUVmax was recorded for lesions, and SUVmean for normal liver uptake. Linear mixed models with random intercept were fitted to evaluate test-retest differences in multiple lesions per patient and to estimate the concordance correlation coefficient. Bland-Altman plots and repeatability coefficients were also produced. Results: In total, 162 lesions (82 bone, 80 soft tissue) were assessed in patients with breast cancer (n = 17) or other cancers (n = 6). Repeat scans within the same institution, using the same scanner or 2 scanners of the same model, had an average difference in SUVmax of 8% (95% confidence interval, 6%-10%). For test-retest on different scanners at different sites, the average difference in lesion SUVmax was 18% (95% confidence interval, 13%-24%). Normal liver uptake (SUVmean) showed an average difference of 5% (95% confidence interval, 3%-10%) for the same scanner model or institution and 6% (95% confidence interval, 3%-11%) for different scanners from different institutions. Protocol adherence was good; the median difference in injection-to-acquisition time was 2 min (range, 0-11 min). Test-retest SUVmax variability was not explained by available information on protocol deviations or patient or lesion characteristics. Conclusion:18F-FDG PET/CT scanner qualification and calibration can yield highly reproducible test-retest tumor SUV measurements. Our data support use of different qualified scanners of the same model for serial studies. Test-retest differences from different scanner models were greater; more resolution-dependent harmonization of scanner protocols and reconstruction algorithms may be capable of reducing these differences to values closer to same-scanner results.

Practical Clinical Measurement of Radiotracer Concentration in Blood: Initial Device Concept and Feasibility Testing.

Kinetic analysis of PET data requires continuous measurement of radioactivity in the arterial blood throughout the acquisition time, termed the arterial input function. The arterial input function is used as an input to compartmental modeling, which can be a better predictor of disease progression than SUV measurements from static PET images. Current common methods of measuring blood concentrations include image-derived, population-based, and manual sampling. These all have challenges due to logistical and technologic issues, as well as patient burden. The aim of this study was to design, develop, and assess a device that is practical and effective for the routine measurement of β-emitting radiotracer concentration in blood without the drawbacks of current methods and for which metabolite analysis is not required. Methods: Designs that integrated a scintillating fiber and a silicon photomultiplier with a general-purpose venous access catheter for in vivo measurement were considered. Other design requirements included miniaturization, high sampling rates, and stopping power for β-particles. Preliminary prototypes were designed to test the feasibility of the concept. Phantom tests were developed to mimic human vasculature. Tests of linearity, sensitivity, signal-to-noise ratios, the impact of vein diameter, and the influence of γ-radiation were conducted. Results: Prototype sensors were constructed using 2 different diameters of polystyrene-based scintillating fibers. Fibers were custom-polished and fixed to a silicon photomultiplier. Sensor output was linear, with R 2 = 0.999 over the range from 0.037 to 9.25 MBq/mL. Absolute sensitivity was approximately 450 counts per second per MBq/mL. Measured signal-to-noise ratios ranged from 1.2:1 to 3.2:1 using a blood-to-tissue concentration ratio of 1:1. Sensor output increased with vein diameter and showed no sensitivity to γ-radiation. Conclusion: In experiments with phantom models, the prototype provided accurate measurements of β-emitting radiotracer concentration. The design will be refined for in vivo testing. The ability to routinely gather blood input function data would facilitate the adoption of kinetic modeling of PET data.

OA146] Underestimation of 68GA PET/CT quantification caused by activity overestimation using default calibrator settings

Purpose It is desirable to achieve accurate quantification in PET/CT imaging as routinely assessed using SUV measurement, including for Gallium-68 (68Ga) labelled tracers. A PET/CT scan of a uniformly filled 68Ga phantom on a GE D710 scanner unexpectedly resulted in a low SUV mean of 0.88, outside of the local tolerance of 1.0 ± 5%. A possible cause of underestimation of quantification is inaccuracy of the activity measurement of 68Ga in the dose calibrator associated with the PET/CT scanner. Methods A source of 68Ga (maximum activity of 599 MBq in 4ml in a P6 vial) was measured in 5 Capintec CRC-55t calibrators (including that used with the D710 PET/CT scanner) using the default 68Ga pre-set calibrator factor of 416. The source was then measured in an externally located Fidelis secondary standard calibrator. Based upon the results, manual adjustments were made to the Capintec factors to match the decay corrected Fidelis measurement. A repeat PET/CT scan of a uniformly filled 68Ga phantom was then performed. Results The cross-calibration results showed that the 5 Capintec calibrators systematically overestimated the activity measurement by 8–9% compared to the Fidelis when using the default factor of 416. The factors were adjusted to 457–463 to match the decay corrected Fidelis measurement. After adjustment of factors, a repeat uniform phantom scan resulted in a SUV mean of 0.97, within the local tolerance. Conclusions Underestimation of PET/CT quantification of 68Ga was caused by overestimation of 68Ga activity measurement using the pre-set dose calibrator factor settings on a Capintec CRC-55t. Improvement in quantification accuracy was achieved by adjusting the calibrator factor based upon an external cross-calibration. Similar results have been recently reported by a group in Australia [1] . We recommend SUV checks using a uniform phantom and regular calibrator cross-calibration exercises for all isotopes used clinically or in clinical trials for quantitative PET/CT imaging.

Dual time-point quantitative SPECT-CT parathyroid imaging using a single computed tomography: feasibility and operator variability.

Dual-phase parathyroid scan with Tc-sestamibi is a standardized imaging method for diagnosing parathyroid adenoma and hyperplasia. Conventional planar images using a gamma camera are performed routinely in early and delayed time points, followed by a single SPECT-CT. SPECT-CT on both early and delayed time points, although clinically useful, is not commonly performed to avoid extra radiation exposure from computed tomography (CT). This study explores the feasibility of co-registering early and delayed SPECT-CT from a single CT and evaluates the most effective combination of images for co-registration. Fourteen retrospective patients with early and delayed planar and SPECT-CT images were recruited for this validation study. Results from contemporaneous early and delayed SPECT-CT, with hardware matched registration, are considered the gold standard. Noncontemporaneous early SPECT with delayed CT and vice versa were also processed with manual alignment by an experienced and a novice operator three times each to evaluate interoperator and intraoperator variability. Maximum standardized uptake values (SUVmax) of the thyroid lobes and parathyroid adenomas were measured, and the results in terms of accuracy and precision from noncontemporaneous SPECT-CT acquisitions were evaluated. Good image quality from co-registered SPECT-CT acquired at different time points with the results showed no bias (P>0.5). The co-registration of early SPECT and delayed CT showed higher precision than the alternative combination. Overall, the experienced operator achieved better precision and intraoperator variability than the novice operator (reproducibility coefficient=33% SUV vs. reproducibility coefficient=54% SUV, P<0.001). Quantitative SUV measurement from early and delayed parathyroid SPECT-CT imaging is feasible, with the best result achieved by experienced operators using delayed CT in manual registration.

Optimal reconstruction matrix and PET image filtration for point-spread function and time-of-flight reconstruction – A phantom study

IntroductionThe aim of this study was to determine the optimal image matrix and half-width of the Gaussian filter after iterative reconstruction of the PET image with point-spread function (PSF) and time-of-flight (TOF) correction, based on measuring the recovery coefficient (RC) curves. The measured RC curves were compared to those from an older system which does not use PSF and TOF corrections. Materials and methodsThe measurements were carried out on a NEMA IEC Body Phantom. We measured the RC curves based on SUVmax and SUVA50 in source spheres with different diameters. The change in noise level for different reconstruction parameter settings and the relation between RC curves and the administered activity were also evaluated. ResultsWith an increasing size of image matrix and reduction in the half-width of the post-reconstruction Gaussian filter, there was a significant increase in image noise and overestimation of the SUV. The local increase in SUV, observed for certain filtrations and objects with a diameter below 13mm, was caused by PSF correction. The decrease in administered activity, while maintaining the same conditions of acquisition and reconstruction, also led to overestimation of readings of the SUV and additionally to deterioration in reproducibility. ConclusionThis study proposes a suitable size for the image matrix and filtering for displaying PET and SUV measurements. The benefits were demonstrated as improved image parameters for the newer instrument, these even being found using relatively strong filtration of the reconstructed images.

18F-FDG PET/CT evaluation of tumor response to the implantation of RENCA macrobeads (RMB) in phase I and II clinical trials [INDBB 10091] in advanced, treatment-resistant metastatic colorectal cancer (mCRC).

e15046 Background: RMB, a cytostatic, biological system form of anti cancer therapy have been used in Ph I &amp; II clinical trials in mCRC w/ evidence of improved survival benefit &amp; QOL. Evaluation of metastatic tumor response by standard CT RECIST criteria however has been unsatisfactory. We hypothesized that using 18F FDG PET/CT scan to evaluate tumor anatomy &amp; metabolism could provide a more accurate picture of tumor response to RMB Methods: 48 mCRC pts (14, Ph 1; 34, Ph 2a) who failed available treatments were implanted intraperitoneally w/ RMB (8mb/kg). Physicals, biomarkers &amp; lab evaluation were obtained at baseline &amp; days 14-90, with PET CT imaging at baseline &amp; day 90. PET scan was acquired 1 hour after FDG injection of 9.4 mCi. CT was used for attenuation correction. Correlation between 18F FDG PET SUVmax findings &amp; CEA &amp; or CA19-9 responses was assessed. Positive response was defined as ≥20% decrease post implant in CEA, CA19-9 &amp; SUV. Only tumors w/ SUVmax ≥ 2.5 were evaluated. SUV measurements were made by 1 radiologist experienced in PET-CT scanning &amp; SUV determination Results: 123 FDG positive mCRC lesions (39, Ph 1; 84 Ph 2a) were detected in 37 evaluable pts (14 m, 23 f; mean age 58.2; SUVmax 2.5-17.5). Of the 37 pts, 28 (76%) showed stabilization &amp; or decreased FDG uptake (4 w/ frank necrosis) as well as stable/decreased CT tumor measurements. Pts w/ pulmonary lesions showed greater responses than those w/ hepatic lesions. 9 (24%) of 37 pts showed increased SUVs. 23 pts (62%) showed decrease in CEA &amp; or CA 19-9 ≥ 20%. 17 pts (74%; 13 decrease, 4 central &amp; peripheral necrosis) had correlation between decreased SUVs/necrosis &amp; biomarkers decrease Conclusions: We conclude SUVs are useful in monitoring mCRC lesions response to RMB therapy. Changes in SUVs correlate w/ CEA &amp; CA 19-9 changes. Taken together the combined data indicate anti tumor effect in these Ph 1/2a trials &amp; offer preliminary support for our hypothesis that 18FDG can be useful in evaluating cell system therapies. Issues of SUVmax standardization &amp; effects of intra tumor heterogeneity however must be considered. Further studies are merited &amp; ongoing, including a planned Ph 3 trial Clinical trial information: NCT01053013; NCT00283075.

SUV navigator enables rapid [18F]-FDG PET/CT image interpretation compared with 2D ROI and 3D VOI evaluations.

Positron emission tomography (PET) and the maximum standardized uptake value (SUVmax) is a useful technique for assessing malignant tumors. Measurements of SUVmax in multiple lesions per patient frequently require many time-consuming procedures. To address this issue, we designed a novel interface named SUV Navigator (SUVnavi), and the purpose of this study was to investigate its utility. We measured SUVmax in 661 lesions from 100 patients with malignant tumors. Diagnoses and SUVmax measurements were made with SUVnavi, 2D, and 3D measurements. SUV measurement accuracy in each method were also evaluated. The average reduction in time with SUVnavi versus 2D was 53.8% and 3D was 37.5%; time required with SUVnavi was significantly shorter than with 2D and 3D (P<0.001 and P<0.001, respectively). The time reduction and lesion number had a positive correlation (P<0.001 and P<0.001, respectively). SUVmax agreed with precise SUVmax in all lesions measured with SUVnavi and 3D but in only 466 of 661 lesions (70.5%) measured with 2D. SUVnavi may be useful for rapid [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) image interpretation without reducing the accuracy of SUVmax measurement.

Quantitation of Cancer Treatment Response by 18F-FDG PET/CT: Multicenter Assessment of Measurement Variability

The aim of this study was to assess the interobserver variability of quantitative 18F-FDG PET/CT parameters used in assessments of treatment response across multiple sites and readers. Methods: Paired pre- and posttreatment 18F-FDG PET/CT images of 30 oncologic patients were distributed to 22 readers across 15 U.S. and international sites. One reader was aware of the full medical history (readreference) of the patients, whereas the 21 other readers were unaware. The readers selected the single hottest tumor from each study, and made SUV measurements from this target lesion and the liver. Descriptive statistics, percentage changes in the measurements, and their agreements were obtained. Results: The intraclass correlation coefficient for the percentage change in SUVmax (%ΔSUVmax) of the hottest tumor was 0.894 (95% confidence interval [CI], 0.813-0.941), and the individual equivalence coefficient was 1.931 (95% CI, 0.568-6.449) when all reads were included (n = 638). When only the measurements that selected the same target tumor as the readreference (n = 486) were included, the intraclass correlation coefficient for the %ΔSUVmax was 0.944 (95% CI, 0.841-0.989), and the individual equivalence coefficient was -0.688 (95% CI, -1.810 to -0.092). The absolute change in SUVmean of liver corrected for lean body mass showed upper and lower limits of agreement (average bias ± 2 SDs) of 0.13 and -0.13 g/mL. Conclusion: The quantitative tumor SUV changes measured across multiple sites and readers show a high correlation. Selection of the same tumor target among readers further increased the degree of correlation.

Characteristics of neuroendocrine neoplasm metastasis in somatostatin receptor PET/CT imaging: a retrospective analysis

Objective To investigate the characteristics of NEN metastasis with SSTR PET/CT and to correlate the results with FDG-PET and pathology. Methods From November 2011 to August 2016, a total of 43 patients with NEN (18 males, 25 females; age range: 26-74 years) were recruited into this retrospective study; they underwent 68Ga-DOTA-TATE PET/CT (TATE-PET) imaging 40-60 min after 44.4-229.4 MBq 68Ga-DOTA-TATE administration. Metastases in 31 patients were confirmed by histopathology and in 12 patients by follow-up and other imaging modalities. Twenty-eight of 43 patients finished routine FDG-PET in a week after TATE-PET. PET/CT results were considered positive when the metastatic lesions were tracer-avid. ROI was drawn over each lesion for size and SUV measurement. χ2 test and Pearson correlation analysis were used for statistical analysis. Results (1) Of 43 patients, TATE-PET detection rates of metastasis in the liver, lymph nodes, bones and lungs were 85.7%(30/35), 12/13, 7/7, 2/3, respectively, with their corresponding SUVmax of 18.1(11.3-23.3), 10.8(5.4-15.6), 7.7(4.2-9.9) and 1.8(1.3-2.3), respectively. Statistical correlation between size and SUVmax was found in metastatic bone lesions(r=0.233, P 0.05. Compared with FDG-PET, TATE-PET was superior in demonstrating metastasis in the liver and bones (70.0%(14/20) vs 65.0%(13/20), 3/3 vs 2/3), equal in detecting lung metastasis (both 2/3) but inferior in demonstrating metastasis in lymph nodes(9/10 vs 10/10). Conclusions The capability of TATE-PET in revealing NEN metastasis varies depending on lesion localization and histologic grade. TATE-PET and FDG-PET are complementary to each other in detection of NEN metastasis, but without obvious relationship to histologic grade. Key words: Neuroendocrine tumors; Carcinoma, neuroendocrine; Neoplasm metastasis; Positron-emission tomography; Tomography, X-ray computed; Gallium radioisotopes; Octreotide; Deoxyglucose

Concordance of 18F-FDG PET Uptake in Tumor and Normal Tissues on PET/MRI and PET/CT.

The aim of this study was to assess the concordance of PET measurements of F-FDG uptake in tumor and normal tissues obtained on Australia's first clinical PET/MRI scanner in comparison to PET/CT, with comparison against published data. One hundred subjects were prospectively recruited from an unselected, heterogeneous group of cancer patients to undergo F-FDG PET/CT and PET/MRI on the same day. SUVs of physiological regions and tumor tissues obtained by PET/MRI and PET/CT were compared and benchmarked against existing published data. Physiological activity was measured in the thoracic aorta and right lobe of the liver. Tumor SUVs were analyzed by cancer type, body region, and a combined group of all lesions. There was an excellent correlation between SUV measurements in tumor lesions obtained by PET/MRI and PET/CT, across all body regions and in all tumor types studied. There was a less robust correlation for SUVs measured in areas of physiological activity, but the level of agreement still fell within 2 SDs of mean. Data from this study showed comparable or smaller systemic biases and narrower confidence limits than existing studies in the literature comparing SUVs from PET/MRI and PET/CT. F-FDG PET/MRI appears promising as an adjunct or alternative to PET/CT for quantitative evaluation in oncology, independent of body region and tumor type, across a wide range of SUVs.

Repeatability of 18F-FLT PET in a Multicenter Study of Patients with High-Grade Glioma.

Quantitative 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET has potential as a noninvasive tumor biomarker for the objective assessment of response to treatment. To guide interpretation of these quantitative data, we evaluated the repeatability of 18F-FLT PET as part of a multicenter trial involving patients with high-grade glioma. Methods:18F-FLT PET was performed on 10 patients with recurrent high-grade glioma at 5 different institutions within the Adult Brain Tumor Consortium trial ABTC1101. Data were acquired according to a double baseline protocol in which PET examinations were repeated within 2 d of each other with no intervening treatment. On each of the 2 imaging days, dedicated brain PET was performed at 2 time points, 1 and 3 h after 18F-FLT administration. Tumor SUVs and related parameters were measured at a central laboratory using various volumes of interest: isocontour at 30% of the maximum pixel (SUVmean_30%), gradient-based segmentation (SUVmean_gradient), the maximum pixel (SUVmax), and a 1-mL sphere at the region of highest uptake (SUVpeak). Repeatability coefficients (RCs) were calculated from the relative differences between corresponding SUV measurements obtained on the 2 d. Results: RCs for tumor SUVs were 22.5% (SUVmean_30%), 23.8% (SUVmean_gradient), 23.2% (SUVmax), and 18.5% (SUVpeak) at 1 h after injection. Corresponding data at 3 h were 22.4%, 25.0%, 27.3%, and 23.6%. Normalizing the tumor SUV data with reference to a background region improved repeatability, and the most stable parameter was the tumor-to-background ratio derived using SUVpeak (RC, 16.5%). Conclusion: SUV quantification of 18F-FLT uptake in glioma had an RC in the range of 18%-24% when imaging began 1 h after 18F-FLT administration. The volume-of-interest methodology had a small but not negligible influence on repeatability, with the best performance obtained using SUVpeak Although changes in 18F-FLT SUV after treatment cannot be directly interpreted as a change in tumor proliferation, we have established ranges beyond which SUV differences are likely due to legitimate biologic effects.

Monitoring of Tumor Growth with [(18)F]-FET PET in a Mouse Model of Glioblastoma: SUV Measurements and Volumetric Approaches.

Noninvasive tumor growth monitoring is of particular interest for the evaluation of experimental glioma therapies. This study investigates the potential of positron emission tomography (PET) using O-(2-18F-fluoroethyl)-L-tyrosine ([18F]-FET) to determine tumor growth in a murine glioblastoma (GBM) model—including estimation of the biological tumor volume (BTV), which has hitherto not been investigated in the pre-clinical context. Fifteen GBM-bearing mice (GL261) and six control mice (shams) were investigated during 5 weeks by PET followed by autoradiographic and histological assessments. [18F]-FET PET was quantitated by calculation of maximum and mean standardized uptake values within a universal volume-of-interest (VOI) corrected for healthy background (SUVmax/BG, SUVmean/BG). A partial volume effect correction (PVEC) was applied in comparison to ex vivo autoradiography. BTVs obtained by predefined thresholds for VOI definition (SUV/BG: ≥1.4; ≥1.6; ≥1.8; ≥2.0) were compared to the histologically assessed tumor volume (n = 8). Finally, individual “optimal” thresholds for BTV definition best reflecting the histology were determined. In GBM mice SUVmax/BG and SUVmean/BG clearly increased with time, however at high inter-animal variability. No relevant [18F]-FET uptake was observed in shams. PVEC recovered signal loss of SUVmean/BG assessment in relation to autoradiography. BTV as estimated by predefined thresholds strongly differed from the histology volume. Strikingly, the individual “optimal” thresholds for BTV assessment correlated highly with SUVmax/BG (ρ = 0.97, p < 0.001), allowing SUVmax/BG-based calculation of individual thresholds. The method was verified by a subsequent validation study (n = 15, ρ = 0.88, p < 0.01) leading to extensively higher agreement of BTV estimations when compared to histology in contrast to predefined thresholds. [18F]-FET PET with standard SUV measurements is feasible for glioma imaging in the GBM mouse model. PVEC is beneficial to improve accuracy of [18F]-FET PET SUV quantification. Although SUVmax/BG and SUVmean/BG increase during the disease course, these parameters do not correlate with the respective tumor size. For the first time, we propose a histology-verified method allowing appropriate individual BTV estimation for volumetric in vivo monitoring of tumor growth with [18F]-FET PET and show that standardized thresholds from routine clinical practice seem to be inappropriate for BTV estimation in the GBM mouse model.