FDG-PET/CT after two cycles of R-CHOP in DLBCL predicts complete remission but has limited value in identifying patients with poor outcome - final result of a UK National Cancer Research Institute prospective study.

The UK National Cancer Research Institute initiated a prospective study (UKCRN-ID 1760) to assess the prognostic value of early fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in diffuse large B-cell lymphoma (DLBCL). In total, 189 patients with DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) had baseline and post-cycle-2 PET (PET2) within a quality assurance framework. Treatment decisions were based on CT; PET2 was archived for central blinded reporting after treatment completion. The association of PET2 response with end-of-treatment CT, progression-free (PFS) and overall survival (OS) was explored. The end-of-treatment complete response rate on CT was 83·9%, 75·0%, 70·5%, 40·4% and 36·4% for Deauville score (DS) 1 (n = 34), 2 (n = 39), 3 (n = 46), 4 (n = 56) and 5 (n = 14) (P < 0·001); and 64·1% and 50·0% for the maximum standardised uptake value (∆SUVmax ) of ≥66% (n = 168) and <66% (n = 21), respectively (P = 0·25). After a median 5·4 years of follow-up, the 5-year PFS was 69·4%, 72·8%, 76·7%, 71·2% and 47·6% by DS 1-5 (P = 0·01); and 72·6% and 57·1% by ∆SUVmax of ≥66% and <66% (P = 0·03), respectively. The association with DS remained in multivariable analyses, and was consistent for OS. Early complete metabolic response (DS 1-3) at interim PET/CT after two cycles of R-CHOP in DLBCL was associated with a higher end-of-treatment complete and overall response rate; however, only DS-5 patients had inferior PFS and OS.

PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

Synthesis and biological evaluation of [(18)F]tetrafluoroborate: a PET imaging agent for thyroid disease and reporter gene imaging of the sodium/iodide symporter.

PURPOSE: The human sodium/iodide symporter (hNIS) is a well-established target in thyroid disease and reporter gene imaging using gamma emitters (123)I-iodide, (131)I-iodide and (99m)Tc-pertechnetate. However, no PET imaging agent is routinely available. The aim of this study was to prepare and evaluate (18)F-labelled tetrafluoroborate ([(18)F]TFB) for PET imaging of hNIS. METHODS: [(18)F]TFB was prepared by isotopic exchange of BF (4) (-) with [(18)F]fluoride in hot hydrochloric acid and purified using an alumina column. Its identity, purity and stability in serum were determined by HPLC, thin-layer chromatography (TLC) and mass spectrometry. Its interaction with NIS was assessed in vitro using FRTL-5 rat thyroid cells, with and without stimulation by thyroid-stimulating hormone (TSH), in the presence and absence of perchlorate. Biodistribution and PET imaging studies were performed using BALB/c mice, with and without perchlorate inhibition. RESULTS: [(18)F]TFB was readily prepared with specific activity of 10 GBq/mg. It showed rapid accumulation in FRTL-5 cells that was stimulated by TSH and inhibited by perchlorate, and rapid specific accumulation in vivo in thyroid (SUV = 72 after 1 h) and stomach that was inhibited 95% by perchlorate. CONCLUSION: [(18)F]TFB is an easily prepared PET imaging agent for rodent NIS and should be evaluated for hNIS PET imaging in humans.

Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma.

PURPOSE: To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries. METHODS: Four centres reported scans from 50 patients with stage II-IV HL, acquired before and after two cycles of Adriamycin/bleomycin/vinblastine/dacarbazine. A five-point scale was used to score response scans using 'normal' mediastinum and liver as reference levels. Centres read scans independently of each other. The level of agreement between centres was determined assuming (1) that uptake in sites involved at diagnosis that was higher than liver uptake represented disease (conservative reading), and (2) that uptake in sites involved at diagnosis that was higher than mediastinal uptake represented disease (sensitive reading). RESULTS: There was agreement that the response scan was 'positive' or 'negative' for lymphoma in 44 patients with a conservative reading and in 41 patients with a sensitive reading. Kappa was 0.85 (95% CI 0.74-0.96) for conservative reading and 0.79 (95% CI 0.67-0.90) for sensitive reading. Agreement was reached in 46 and 44 patients after discussion for the conservative and sensitive readings, respectively. CONCLUSION: The criteria developed for reporting in the RATHL trial are sufficiently robust to be used in a multicentre setting.

[18F]FDG PET/CT in the diagnosis of malignant peripheral nerve sheath tumours in neurofibromatosis type-1.

PURPOSE: The detection of malignant peripheral nerve sheath tumours (MPNSTs) in patients with neurofibromatosis 1 (NF1) remains a clinical challenge. The purpose of this study was to evaluate the use of [(18)F]2-fluoro-2-deoxy-D-glucose PET/CT (FDG PET/CT with early and delayed imaging) in patients with symptomatic neurofibromas, to revalidate current cut-off values for identification of malignant change within neurofibromas and to examine the relationship between SUV and tumour grade. METHODS: Patients with symptomatic neurofibromas underwent FDG PET/CT imaging at 90 and 240 min. Semiquantitative analysis using maximum standardized uptake value (SUVmax) was performed and correlated with histology. RESULT: In 69 patients, 85 lesions were identified for analysis, including 10 atypical neurofibromas and 21 MPNSTs. Sensitivity of FDG PET/CT in diagnosing NF1-associated MPNST was 0.97 (95% CI 0.81-0.99) and the specificity was 0.87 (CI 0.74-0.95). There was a significant difference in SUVmax between early and delayed imaging and in SUVmax between tumours identified as benign and malignant on PET/CT. There was also a significant difference in SUVmax between tumour grades. CONCLUSION: FDG PET/CT is a highly sensitive and specific imaging modality for the diagnosis of MPNST in NF1 patients. We recommend performing early (90 min) and delayed imaging at 4 h for accurate lesion characterization and using a cut-off SUVmax of 3.5 on delayed imaging to achieve maximal sensitivity.

Observer variation in FDG PET-CT for staging of non-small-cell lung carcinoma.

PURPOSE: Error and variation in reporting remains one of the weakest features of clinical imaging despite enormous technological advances in nuclear medicine and radiology. The aim of this study was to evaluate agreement amongst experienced readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. METHODS: A series of (18)F-FDG PET-CT scans from 100 consecutive patients were reviewed independently by three experienced readers, with two readers reviewing each scan series a second time. Individual mediastinal lymph node stations were assessed as benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also assigned. Kappa (kappa) was used to compare ratings from two categories and weighted kappa (kappa(w)) for three or more categories, and kappa values were interpreted according to the Landis-Koch benchmarks. RESULTS: Both intra- and interobserver agreement for N and M staging were high. For M staging there was almost perfect intra- and interobserver agreement (kappa = 0.90-0.93). For N staging, agreement was either almost perfect or substantial (intraobserver kappa(w) = 0.79, 0.91; interobserver kappa(w) = 0.75-0.81). Importantly, there was almost perfect agreement for N0/1 vs N2/3 disease (kappa = 0.80-0.97). Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9) was either almost perfect or substantial (kappa(w) = 0.71-0.88), but lower for hilar nodes (10; kappa(w) = 0.56-0.71). Interreporter variability was greatest for aortopulmonary nodes (5, 6; kappa(w) = 0.48-0.55). CONCLUSION: Amongst experienced reporters in a single centre, there was a very high level of agreement for both mediastinal nodal stage and detection of distant metastases with PET-CT. This supports the use of PET-CT as a robust imaging modality for staging NSCLC.

Retrospective data-driven respiratory gating for PET/CT.

Respiratory motion can adversely affect both PET and CT acquisitions. Respiratory gating allows an acquisition to be divided into a series of motion-reduced bins according to the respiratory signal, which is typically hardware acquired. In order that the effects of motion can potentially be corrected for, we have developed a novel, automatic, data-driven gating method which retrospectively derives the respiratory signal from the acquired PET and CT data. PET data are acquired in listmode and analysed in sinogram space, and CT data are acquired in cine mode and analysed in image space. Spectral analysis is used to identify regions within the CT and PET data which are subject to respiratory motion, and the variation of counts within these regions is used to estimate the respiratory signal. Amplitude binning is then used to create motion-reduced PET and CT frames. The method was demonstrated with four patient datasets acquired on a 4-slice PET/CT system. To assess the accuracy of the data-derived respiratory signal, a hardware-based signal was acquired for comparison. Data-driven gating was successfully performed on PET and CT datasets for all four patients. Gated images demonstrated respiratory motion throughout the bin sequences for all PET and CT series, and image analysis and direct comparison of the traces derived from the data-driven method with the hardware-acquired traces indicated accurate recovery of the respiratory signal.

Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study.

PURPOSE: Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) -adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes. PATIENTS AND METHODS: Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS). RESULTS: High PET score was associated with inferior EFS, before (P < .001) and after adjustment (P = .01) for baseline risk stratification. Only patients with a postchemotherapy PET score of 5 (uptake ≥ three times maximum liver uptake) had an increased risk of progression or HL-related death (hazard ratio, 9.4 v score of 3; 95% CI, 2.8 to 31.3 and hazard ratio, 6.7 v score of 4; 95% CI, 1.4 to 31.7). Patients with a PET score of 5 also had inferior progression-free and overall survival. There was no association between European Organisation for Research and Treatment of Cancer or German Hodgkin Study Group risk group and EFS, before or after adjusting for PET score (all P > .4). CONCLUSION: In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL.

Use of the CT component of PET-CT to improve PET-MR registration: demonstration in soft-tissue sarcoma.

We have investigated improvements to PET-MR image registration offered by PET-CT scanning. Ten subjects with suspected soft-tissue sarcomas were scanned with an in-line PET-CT and a clinical MR scanner. PET to CT, CT to MR and PET to MR image registrations were performed using a rigid-body external marker technique and rigid and non-rigid voxel-similarity algorithms. PET-MR registration was also performed using transformations derived from the registration of CT to MR. The external marker technique gave fiducial registration errors of 2.1 mm, 5.1 mm and 5.3 mm for PET-CT, PET-MR and CT-MR registration. Target registration errors were 3.9 mm, 9.0 mm and 9.3 mm, respectively. Voxel-based algorithms were evaluated by measuring the distance between corresponding fiducials after registration. Registration errors of 6.4 mm, 14.5 mm and 9.5 mm, respectively, for PET-CT, PET-MR and CT-MR were observed for rigid-body registration while non-rigid registration gave errors of 6.8 mm, 16.3 mm and 7.6 mm for the same modality combinations. The application of rigid and non-rigid CT to MR transformations to accompanying PET data gives significantly reduced PET-MR errors of 10.0 mm and 8.5 mm, respectively. Visual comparison by two independent observers confirmed the improvement over direct PET-MR registration. We conclude that PET-MR registration can be more accurately and reliably achieved using the hybrid technique described than through direct rigid-body registration of PET to MR.

18F-Tetrafluoroborate, a PET Probe for Imaging Sodium/Iodide Symporter Expression: Whole-Body Biodistribution, Safety, and Radiation Dosimetry in Thyroid Cancer Patients.

We report the safety, biodistribution, and internal radiation dosimetry, in humans with thyroid cancer, of 18F-tetrafluoroborate (18F-TFB), a novel PET radioligand for imaging the human sodium/iodide symporter (hNIS). Methods: Serial whole-body PET scans of 5 subjects with recently diagnosed thyroid cancer were acquired before surgery for up to 4 h after injection of 184 ± 15 MBq of 18F-TFB. Activity was determined in whole blood, plasma, and urine. Mean organ-absorbed doses and effective doses were calculated via quantitative image analysis and using OLINDA/EXM software. Results: Images showed a high uptake of 18F-TFB in known areas of high hNIS expression (thyroid, salivary glands, and stomach). Excretion was predominantly renal. No adverse effects in relation to safety of the radiopharmaceutical were observed. The effective dose was 0.0326 ± 0.0018 mSv/MBq. The critical tissues/organs receiving the highest mean sex-averaged absorbed doses were the thyroid (0.135 ± 0.079 mSv/MBq), stomach (0.069 ± 0.022 mSv/MBq), and salivary glands (parotids, 0.031 ± 0.011 mSv/MBq; submandibular, 0.061 ± 0.031 mSv/MBq). Other organs of interest were the bladder (0.102 ± 0.046 mSv/MBq) and kidneys (0.029 ± 0.009 mSv/MBq). Conclusion: Imaging using 18F-TFB imparts a radiation exposure similar in magnitude to many other 18F-labeled radiotracers. 18F-TFB shows a biodistribution similar to 99mTc-pertechnetate, a known nonorganified hNIS tracer, and is pharmacologically and radiobiologically safe in humans. Phase 2 trials for 18F-TFB as an hNIS imaging agent are warranted.

Large variations occur in bone density measurements of children when using different software.

BACKGROUND: Paediatric dual X-ray absorptiometry (DXA) studies present a number of technical problems. One of these is that the edge detection algorithms designed for the adult skeleton may fail for paediatric studies. Hologic provide alternative algorithms for low bone density studies. AIM: To assess low-density software for the analysis of paediatric DXA studies and to compare with the adult protocol. METHODS: Our centre has scanned 450 normal children as part of a normal range study. A subgroup of 103 children was selected using a random number generator. The group was distributed evenly between males and females and across the age range 5-17 years. Each individual underwent both a lumbar spine and a whole-body scan on a Hologic QDR-4500W DXA scanner. Both scans were analysed using the standard adult protocol and then re-analysed using the Hologic experimental paediatric protocol for whole body and the Hologic low-density protocol for lumbar spine. RESULTS: Both lumbar spine protocols showed an increase in bone mineral density with age; however, the low-density protocol always produced a lower bone mineral density result than the adult protocol. Bland-Altman analysis showed limits of agreement of 0.031-0.093 g x cm(-2) (male, 0.032-0.089 g x cm(-2); female, 0.031-0.096 g x cm(-2)). This represents a mean difference of 9%. Five results showed differences greater than the upper limit of agreement. All these cases were children under 11 years of age who had large areas of spine not identified as bone by the adult protocol. These children were all below the 30th percentile for the body mass index. The whole-body protocols showed similar increases in bone mineral density with age; however, the experimental paediatric protocol always produced a lower bone mineral density result than the adult protocol. Paired results showed limits of agreement of 0.0668-0.130 g x cm(-2) (male, 0.063-0.124 g x cm(-2); female, 0.073-0.134 g x cm(-2)). This represents a mean difference of 11%. Five results showed differences greater than the upper limit of agreement. CONCLUSIONS: For anteroposterior (AP) lumbar spine scans, the use of the paediatric algorithm in children under 11 years of age would prevent the largest failures in analysis. For whole-body scanning, the adult algorithm showed no major failures in children of 11 years or older. It is hoped that forthcoming improvements in whole-body density analysis will improve the results for those under 11 years of age. Normal range data should be generated for any new algorithm to allow proper interpretation of clinical studies.

False Discovery Rates in PET and CT Studies with Texture Features: A Systematic Review.

PURPOSE: A number of recent publications have proposed that a family of image-derived indices, called texture features, can predict clinical outcome in patients with cancer. However, the investigation of multiple indices on a single data set can lead to significant inflation of type-I errors. We report a systematic review of the type-I error inflation in such studies and review the evidence regarding associations between patient outcome and texture features derived from positron emission tomography (PET) or computed tomography (CT) images. METHODS: For study identification PubMed and Scopus were searched (1/2000-9/2013) using combinations of the keywords texture, prognostic, predictive and cancer. Studies were divided into three categories according to the sources of the type-I error inflation and the use or not of an independent validation dataset. For each study, the true type-I error probability and the adjusted level of significance were estimated using the optimum cut-off approach correction, and the Benjamini-Hochberg method. To demonstrate explicitly the variable selection bias in these studies, we re-analyzed data from one of the published studies, but using 100 random variables substituted for the original image-derived indices. The significance of the random variables as potential predictors of outcome was examined using the analysis methods used in the identified studies. RESULTS: Fifteen studies were identified. After applying appropriate statistical corrections, an average type-I error probability of 76% (range: 34-99%) was estimated with the majority of published results not reaching statistical significance. Only 3/15 studies used a validation dataset. For the 100 random variables examined, 10% proved to be significant predictors of survival when subjected to ROC and multiple hypothesis testing analysis. CONCLUSIONS: We found insufficient evidence to support a relationship between PET or CT texture features and patient survival. Further fit for purpose validation of these image-derived biomarkers should be supported by appropriate biological and statistical evidence before their association with patient outcome is investigated in prospective studies.

Role of ¹8F-FDG PET imaging in paediatric primary dystonia and dystonia arising from neurodegeneration with brain iron accumulation.

PURPOSE: No current neuroimaging modality offers mechanistic or prognostic information to guide management in paediatric dystonia. We assessed F-fluorodeoxyglucose (¹8F-FDG) PET/computed tomography (CT) brain imaging in childhood primary dystonia (PDS) and neurodegeneration with brain iron accumulation (NBIA) to determine whether it would identify altered metabolism and hence constitute a potentially useful 'biomarker' indicating functional disturbances associated with dystonia and severity of the disease. MATERIALS AND METHODS: A total of 27 children (15 PDS and 12 NBIA) underwent brain ¹8F-FDG PET/CT imaging under anaesthesia during acquisition. The images were assessed visually and the two groups were compared quantitatively with statistical parametric mapping. PET/CT images were spatially transformed to Montreal Neurological Institute standard space. Voxelwise ¹8F-FDG uptake was normalized to whole-brain uptake. Data of both groups were correlated separately with duration and severity of dystonia as assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: Visual inspection did not identify any abnormalities in ¹8F-FDG uptake within the cerebral cortex, basal ganglia, or thalami in either group. Quantitative analysis identified higher uptake in the posterior cingulate and bilateral posterior putamina but decreased uptake in the occipital cortex and cerebellum in NBIA compared with PDS. The NBIA group had more severe dystonia scores compared with the PDS group. BFMDRS was negatively correlated with age but not with duration of dystonia. CONCLUSION: Compared with PDS, NBIA is dominated by relative overactivity in the putamen and by cerebellar underactivity, patterns that may reflect the increased severity of dystonia in NBIA cases. Hence, there is a potential role for ¹8F-FDG PET/CT imaging in paediatric dystonia, particularly in the NBIA group.

A method for accurate spatial registration of PET images and histopathology slices.

BACKGROUND: Accurate alignment between histopathology slices and positron emission tomography (PET) images is important for radiopharmaceutical validation studies. Limited data is available on the registration accuracy that can be achieved between PET and histopathology slices acquired under routine pathology conditions where slices may be non-parallel, non-contiguously cut and of standard block size. The purpose of this study was to demonstrate a method for aligning PET images and histopathology slices acquired from patients with laryngeal cancer and to assess the registration accuracy obtained under these conditions. METHODS: Six subjects with laryngeal cancer underwent a (64)Cu-copper-II-diacetyl-bis(N4-methylthiosemicarbazone) ((64)Cu-ATSM) PET computed tomography (CT) scan prior to total laryngectomy. Sea urchin spines were inserted into the pathology specimen to act as fiducial markers. The specimen was fixed in formalin, as per standard histopathology operating procedures, and was then CT scanned and cut into millimetre-thick tissue slices. A subset of the tissue slices that included both tumour and fiducial markers was taken and embedded in paraffin blocks. Subsequently, microtome sectioning and haematoxylin and eosin staining were performed to produce 5-µm-thick tissue sections for microscopic digitisation. A series of rigid registration procedures was performed between the different imaging modalities (PET; in vivo CT-i.e. the CT component of the PET-CT; ex vivo CT; histology slices) with the ex vivo CT serving as the reference image. In vivo and ex vivo CTs were registered using landmark-based registration. Histopathology and ex vivo CT images were aligned using the sea urchin spines with additional anatomical landmarks where available. Registration errors were estimated using a leave-one-out strategy for in vivo to ex vivo CT and were estimated from the RMS landmark accuracy for histopathology to ex vivo CT. RESULTS: The mean ± SD accuracy for registration of the in vivo to ex vivo CT images was 2.66 ± 0.66 mm, and the accuracy for registration of histopathology to ex vivo CT was 0.86 ± 0.41 mm. Estimating the PET to in vivo CT registration accuracy to equal the PET-CT alignment accuracy of 1 mm resulted in an overall average registration error between PET and histopathology slices of 3.0 ± 0.7 mm. CONCLUSIONS: We have developed a registration method to align PET images and histopathology slices with an accuracy comparable to the spatial resolution of the PET images.

Multicenter Reproducibility of 18F-Fluciclatide PET Imaging in Subjects with Solid Tumors.

UNLABELLED: Integrins are upregulated on both tumor cells and associated vasculature, where they play an important role in angiogenesis and metastasis. Fluciclatide is an arginine-glycine-aspartic acid peptide with high affinity for αvß3/αvß5 integrin, which can be radiolabeled for PET imaging of angiogenesis. Thus, (18)F-fluciclatide is a potential biomarker of therapeutic response to antiangiogenic inhibitors. The aim of this study was to evaluate the reproducibility of (18)F-fluciclatide in multiple solid-tumor types. METHODS: Thirty-nine patients underwent PET/CT scanning at 40, 65, and 90 min after injection of (18)F-fluciclatide (maximum, 370 MBq) on 2 separate days (2-9 d apart). Patients did not receive any therapy between PET/CT scans. (18)F-fluciclatide images were reported and quantitative measures of uptake were extracted using the PERCIST methodology. Intrasubject reproducibility of PET uptake in all measurable lesions was evaluated by calculating relative differences in SUV between PET scans for each lesion during the 2 imaging sessions. RESULTS: Thirty-nine measurable lesions were detected in 26 patients. Lesion uptake correlated strongly across imaging sessions (r = 0.92, P < 0.05, at 40 min; r = 0.94, P < 0.05, at 65 min; r = 0.94, P < 0.05, at 90 min) with a mean relative difference and SD of the relative difference of 0.006 ± 0.18 at 40 min, 0.003 ± 0.19 at 65 min, and 0.025 ± 0.20 at 90 min. This reflects 95% limits of repeatability of 35%-39% for the difference between the 2 SUV measurements or a variability of 18%-20% in agreement from that observed in well-calibrated multicenter (18)F-FDG studies. CONCLUSION: The test-retest reproducibility of (18)F-fluciclatide across multiple tumor types has been measured and shown to be acceptable. This is an important step in the development of this in vivo biomarker to identify and quantify response to antiangiogenic therapy in cancer patients.

Optimization of parathyroid imaging by simultaneous dual energy planar and single photon emission tomography.

BACKGROUND: Single photon emission tomography (SPET) gives valuable 3-dimensional information, but prolongs the time of imaging and increases the possibility of patient movement. We therefore investigated a method for the optimization of SPET. METHOD: Using an in-house fabricated thyroid/parathyroid neck phantom simultaneous dual energy (DE) 1223I/99mTc imaging to localize parathyroid glands was assessed both in planar and SPET modes. RESULTS: Experiments demonstrated improved spatial resolution and contrast for planar pinhole imaging compared to parallel collimation. For DE-SPET compared to planar pinhole imaging more glands in the phantom were visualized by the improved contrast. CONCLUSION: We conclude that DE-SPET for parathyroid imaging is feasible to aid the accurate localization of parathyroid adenomas. For planar imaging pinhole collimation is superior to parallel hole collimation.

Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group.

PURPOSE: Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response­adapted treatment guided by early interim positron emission tomography (PET)­computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely. METHODS: An imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research in progress, and identify key areas for research pertaining to imaging and lymphoma. RESULTS: A working paper was circulated for comment and presented at the Fourth International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in Lugano, Switzerland, to update the International Harmonisation Project guidance regarding PET. Recommendations were made to optimize the use of PET-CT in staging and response assessment of lymphoma, including qualitative and quantitative methods. CONCLUSION: This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials.

Comparing approaches to correct for respiratory motion in NH3 PET-CT cardiac perfusion imaging.

AIM: Respiratory motion affects cardiac PET-computed tomography (CT) imaging by reducing attenuation correction (AC) accuracy and by introducing blur. The aim of this study was to compare three approaches for reducing motion-induced AC errors and evaluate the inclusion of respiratory motion correction. MATERIALS AND METHODS: AC with a helical CT was compared with averaged cine and gated cine CT, as well as with a pseudo-gated CT, which was produced by applying PET-derived motion fields to the helical CT. Data-driven gating was used to produce respiratory-gated PET and CT images, and 60 NH3 PET scans were attenuation corrected with each of the CTs. Respiratory motion correction was applied to the gated and pseudo-gated attenuation-corrected PET images. RESULTS: Anterior and lateral wall intensity measured in attenuation-corrected PET images generally increased when PET-CT alignment improved and decreased when alignment degraded. On average, all methods improved PET-CT liver and cardiac alignment, and increased anterior wall intensity by more than 10% in 36, 33 and 25 cases for the averaged, gated and pseudo-gated CTAC PET images, respectively. However, cases were found where alignment worsened and severe artefacts resulted. This occurred in more cases and to a greater extent for the averaged and gated CT, where the anterior wall intensity reduced by more than 10% in 21 and 24 cases, respectively, compared with six cases for the pseudo-gated CT. Application of respiratory motion correction increased the average anterior and inferior wall intensity, but only 13% of cases increased by more than 10%. CONCLUSION: All methods improved average respiratory-induced AC errors; however, some severe artefacts were produced. The pseudo-gated CT was found to be the most robust method.

Implications of a positive sentinel node in oral squamous cell carcinoma.

BACKGROUND: The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome. METHODS: In all, 109 patients (n = 109) from 15 European centers, with cT1/2,N0 tumors, and a positive sentinel lymph node were identified. Kaplan-Meier and univariate and multivariate logistic regression analysis were used to identify variables that predicted for additional positive nodes and their position within the neck. RESULTS: A total of 122 neck dissections were performed in 109 patients. Additional positive nodes were found in 34.4% of cases (42/122: 18 same, 21 adjacent, and 3 nonadjacent neck level). Additional nodes, especially if outside the sentinel node basin, had an impact on outcome. CONCLUSIONS: The results are preliminary but suggest that both the number and the position of positive sentinel nodes may identify different prognostic groups that may allow further tailoring of management plans.