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Immuno-positron emission tomography (immunoPET) enables imaging of specific targets that play a role in targeted therapy and immunotherapy, such as antigens on cell membranes, targets in the disease microenvironment, or immune cells. The most common immunoPET applications use a monoclonal antibody labeled with a relatively long-lived positron emitter such as 89Zr (T1/2= 78.4 h), but smaller antibody-based constructs labeled with various other positron emitting radionuclides are also being investigated. This molecular imaging technique can thus guide the development of new drugs and may have a pivotal role in selecting patients for a particular therapy. In early phase immunoPET trials, multiple imaging time points are used to examine the time-dependent biodistribution and to determine the optimal imaging time point, which may be several days after tracer injection due to the slow kinetics of larger molecules. Once this has been established, usually only one static scan is performed and semi-quantitative values are reported. However, total PET uptake of a tracer is the sum of specific and nonspecific uptake. In addition, uptake may be affected by other factors such as perfusion, pre-/co-administration of the unlabeled molecule, and the treatment schedule. This article reviews imaging methodologies used in immunoPET studies and is divided into two parts. The first part summarizes the vast majority of clinical immunoPET studies applying semi-quantitative methodologies. The second part focuses on a handful of studies applying pharmacokinetic models and includes preclinical and simulation studies. Finally, the potential and challenges of immunoPET quantification methodologies are discussed within the context of the recent technological advancements provided by long axial field of view PET/CT scanners. [ABSTRACT FROM AUTHOR]

Purpose: Accurate preoperative localization is imperative to guide surgery in primary hyperparathyroidism (pHPT). It remains unclear which second-line imaging technique is most effective after negative first-line imaging. In this study, we compare the diagnostic effectiveness of [11C]methionine PET/CT, [11C]choline PET/CT, and four dimensional (4D)-CT head-to-head in patients with pHPT, to explore which of these imaging techniques to use as a second-line scan. Methods: We conducted a powered, prospective, blinded cohort study in patients with biochemically proven pHPT and prior negative or discordant first-line imaging consisting of ultrasonography and 99mTc-sestamibi. All patients underwent [11C]methionine PET/CT, [11C]choline PET/CT, and 4D-CT. At first, all scans were interpreted by a nuclear medicine physician, and a radiologist who were blinded from patient data and all imaging results. Next, a non-blinded scan reading was performed. The scan results were correlated with surgical and histopathological findings. Serum calcium values at least 6 months after surgery were used as gold standard for curation of HPT. Results: A total of 32 patients were included in the study. With blinded evaluation, [11C]choline PET/CT was positive in 28 patients (88%), [11C]methionine PET/CT in 23 (72%), and 4D-CT in 15 patients (47%), respectively. In total, 30 patients have undergone surgery and 32 parathyroid lesions were histologically confirmed as parathyroid adenomas. Based on the blinded evaluation, lesion-based sensitivity of [11C]choline PET/CT, [11C]methionine PET/CT, and 4D-CT was respectively 85%, 67%, and 39%. The sensitivity of [11C]choline PET/CT differed significantly from that of [11C]methionine PET/CT and 4D-CT (p = 0.031 and p < 0.0005, respectively). Conclusion: In the setting of pHPT with negative first-line imaging, [11C]choline PET/CT is superior to [11C]methionine PET/CT and 4D-CT in localizing parathyroid adenomas, allowing correct localization in 85% of adenomas. Further studies are needed to determine cost–benefit and efficacy of these scans, including the timing of these scans as first- or second-line imaging techniques. [ABSTRACT FROM AUTHOR]

Background: In metastatic breast cancer (MBC), [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) can be used for staging. We evaluated the correlation between BC histopathological characteristics and [18F]FDG uptake in corresponding metastases. Patients and Methods: Patients with non-rapidly progressive MBC of all subtypes prospectively underwent a baseline histological metastasis biopsy and [18F]FDG-PET. Biopsies were assessed for estrogen, progesterone, and human epidermal growth factor receptor 2 (ER, PR, HER2); Ki-67; and histological subtype. [18F]FDG uptake was expressed as maximum standardized uptake value (SUVmax) and results were expressed as geometric means. Results: Of 200 patients, 188 had evaluable metastasis biopsies, and 182 of these contained tumor. HER2 positivity and Ki-67 ≥ 20% were correlated with higher [18F]FDG uptake (estimated geometric mean SUVmax 10.0 and 8.8, respectively; p = 0.0064 and p = 0.014). [18F]FDG uptake was lowest in ER-positive/HER2-negative BC and highest in HER2-positive BC (geometric mean SUVmax 6.8 and 10.0, respectively; p = 0.0058). Although [18F]FDG uptake was lower in invasive lobular carcinoma (n = 31) than invasive carcinoma NST (n = 146) (estimated geometric mean SUVmax 5.8 versus 7.8; p = 0.014), the metastasis detection rate was similar. Conclusions: [18F]FDG-PET is a powerful tool to detect metastases, including invasive lobular carcinoma. Although BC histopathological characteristics are related to [18F]FDG uptake, [18F]FDG-PET and biopsy remain complementary in MBC staging (NCT01957332). [ABSTRACT FROM AUTHOR]

Background: The use of computed tomography (CT) for attenuation correction (AC) in whole‐body PET/CT can result in a significant contribution to radiation exposure. This can become a limiting factor for reducing considerably the overall radiation exposure of the patient when using the new long axial field of view (LAFOV) PET scanners. However, recent CT technology have introduced features such as the tin (Sn) filter, which can substantially reduce the CT radiation dose. Purpose: The purpose of this study was to investigate the ultra‐low dose CT for attenuation correction using the Sn filter together with other dose reduction options such as tube current (mAs) reduction. We explore the impact of dose reduction in the context of AC‐CT and how it affects PET image quality. Methods: The study evaluated a range of ultra‐low dose CT protocols using five physical phantoms that represented a broad collection of tissue electron densities. A long axial field of view (LAFOV) PET/CT scanner was used to scan all phantoms, applying various CT dose reduction parameters such as reducing tube current (mAs), increasing the pitch value, and applying the Sn filter. The effective dose resulting from the CT scans was determined using the CTDIVol reported by the scanner. Several voxel‐based and volumes of interest (VOI)‐based comparisons were performed to compare the ultra‐low dose CT images, the generated attenuation maps, and corresponding PET images against those images acquired with the standard low dose CT protocol. Finally, two patient datasets were acquired using one of the suggested ultra‐low dose CT settings. Results: By incorporating the Sn filter and adjusting mAs to the lowest available value, the radiation dose in CT images of PBU‐60 phantom was significantly reduced; resulting in an effective dose of nearly 2% compared to the routine low dose CT protocols currently in clinical use. The assessment of PET images using VOI and voxel‐based comparisons indicated relative differences (RD%) of under 6% for mean activity concentration (AC) in the torso phantom and patient dataset and under 8% for a source point in the CIRS phantom. The maximum RD% value of AC was 14% for the point source in the CIRS phantom. Increasing the tube current from 6 mAs to 30 mAs in patients with high BMI, or with arms down, can suppress the photon starvation artifact, whilst still preserving a dose reduction of 90%. Conclusions: Introducing a Sn filter in CT imaging lowers radiation dose by more than 90%. This reduction has minimal effect on PET image quantification at least for patients without Body Mass Index (BMI) higher than 30. Notably, this study results need validation using a larger clinical PET/CT dataset in the future, including patients with higher BMI. [ABSTRACT FROM AUTHOR]

Purpose : Monoclonal antibody (mAb)-based PET (immunoPET) imaging can characterise tumour lesions non-invasively. It may be a valuable tool to determine which patients may benefit from treatment with a specific monoclonal antibody (mAb) and evaluate treatment response. For 89Zr immunoPET imaging, higher sensitivity of state-of-the art PET/CT systems equipped with silicon photomultiplier (SiPM)-based detector elements may be beneficial as the low positron abundance of 89Zr causes a low signal-to-noise level. Moreover, the long physical half-life limits the amount of activity that can be administered to the patients leading to poor image quality even when using long scan durations. Here, we investigated the difference in semiquantitative performance between the PMT-based Biograph mCT, our clinical reference system, and the SiPM-based Biograph Vision PET/CT in 89Zr immunoPET imaging. Furthermore, the effects of scan duration reduction using the Vision on semiquantitative imaging parameters and its influence on image quality assessment were evaluated. Methods: Data were acquired on day 4 post 37 MBq 89Zr-labelled mAb injection. Five patients underwent a double scan protocol on both systems. Ten patients were scanned only on the Vision. For PET image reconstruction, three protocols were used, i.e. one camera-dependent protocol and European Association of Nuclear Medicine Research Limited (EARL) standards 1 and 2 compliant protocols. Vision data were acquired in listmode and were reprocessed to obtain images at shorter scan durations. Semiquantitative PET image parameters were derived from tumour lesions and healthy tissues to assess differences between systems and scan durations. Differently reconstructed images obtained using the Vision were visually scored regarding image quality by two nuclear medicine physicians. Results: When images were reconstructed using 100% acquisition time on both systems following EARL standard 1 compliant reconstruction protocols, results regarding semiquantification were comparable. For Vision data, reconstructed images that conform to EARL1 standards still resulted in comparable semiquantification at shorter scan durations (75% and 50%) regarding 100% acquisition time. Conclusion: Scan duration of 89Zr immunoPET imaging using the Vision can be decreased up to 50% compared with using the mCT while maintaining image quality using the EARL1 compliant reconstruction protocol. [ABSTRACT FROM AUTHOR]

Purpose: Current European Association of Nuclear Medicine (EANM) Research Ltd. (EARL) guidelines for the standardisation of PET imaging developed for conventional systems have not yet been adjusted for long axial field-of-view (LAFOV) systems. In order to use the LAFOV Siemens Biograph Vision Quadra PET/CT (Siemens Healthineers, Knoxville, TN, USA) in multicentre research and harmonised clinical use, compliance to EARL specifications for 18F-FDG tumour imaging was explored in the current study. Additional tests at various locations throughout the LAFOV and the use of shorter scan durations were included. Furthermore, clinical data were collected to further explore and validate the effects of reducing scan duration on semi-quantitative PET image biomarker accuracy and precision when using EARL-compliant reconstruction settings. Methods: EARL compliance phantom measurements were performed using the NEMA image quality phantom both in the centre and at various locations throughout the LAFOV. PET data (maximum ring difference (MRD) = 85) were reconstructed using various reconstruction parameters and reprocessed to obtain images at shorter scan durations. Maximum, mean and peak activity concentration recovery coefficients (RC) were obtained for each sphere and compared to EARL standards specifications. Additionally, PET data (MRD = 85) of 10 oncological patients were acquired and reconstructed using various reconstruction settings and reprocessed from 10 min listmode acquisition into shorter scan durations. Per dataset, SUVs were derived from tumour lesions and healthy tissues. ANOVA repeated measures were performed to explore differences in lesion SUVmax and SUVpeak. Wilcoxon signed-rank tests were performed to evaluate differences in background SUVpeak and SUVmean between scan durations. The coefficient of variation (COV) was calculated to characterise noise. Results: Phantom measurements showed EARL compliance for all positions throughout the LAFOV for all scan durations. Regarding patient data, EARL-compliant images showed no clinically meaningful significant differences in lesion SUVmax and SUVpeak or background SUVmean and SUVpeak between scan durations. Here, COV only varied slightly. Conclusion: Images obtained using the Vision Quadra PET/CT comply with EARL specifications. Scan duration and/or activity administration can be reduced up to a factor tenfold without the interference of increased noise. [ABSTRACT FROM AUTHOR]

Background: Excellent performance characteristics of the Vision Quadra PET/CT, e.g. a substantial increase in sensitivity, allow for precise measurements of image-derived input functions (IDIF) and tissue time activity curves. Previously we have proposed a method for a reduced 30 min (as opposed to 60 min) whole body 18F-FDG Patlak PET imaging procedure using a previously published population-averaged input function (PIF) scaled to IDIF values at 30–60 min post-injection (p.i.). The aim of the present study was to apply this method using the Vision Quadra PET/CT, including the use of a PIF to allow for shortened scan durations. Methods: Twelve patients with suspected lung malignancy were included and received a weight-based injection of 18F-FDG. Patients underwent a 65-min dynamic PET acquisition which were reconstructed using European Association of Nuclear Medicine Research Ltd. (EARL) standards 2 reconstruction settings. A volume of interest (VOI) was placed in the ascending aorta (AA) to obtain the IDIF. An external PIF was scaled to IDIF values at 30–60, 40–60, and 50–60 min p.i., respectively, and parametric 18F-FDG influx rate constant (Ki) images were generated using a t* of 30, 40 or 50 min, respectively. Herein, tumour lesions as well as healthy tissues, i.e. liver, muscle tissue, spleen and grey matter, were segmented. Results: Good agreement between the IDIF and corresponding PIF scaled to 30–60 min p.i. and 40–60 min p.i. was obtained with 7.38% deviation in Ki. Bland–Altman plots showed excellent agreement in Ki obtained using the PIF scaled to the IDIF at 30–60 min p.i. and at 40–60 min p.i. as all data points were within the limits of agreement (LOA) (− 0.004–0.002, bias: − 0.001); for the 50–60 min p.i. Ki, all except one data point fell in between the LOA (− 0.021–0.012, bias: − 0.005). Conclusions: Parametric whole body 18F-FDG Patlak Ki images can be generated non-invasively on a Vision Quadra PET/CT system. In addition, using a scaled PIF allows for a substantial (factor 2 to 3) reduction in scan time without substantial loss of accuracy (7.38% bias) and precision (image quality and noise interference). [ABSTRACT FROM AUTHOR]

Background: 6-[18F]fluoro-l-3,4-dihydroxyphenyl alanine ([18F]FDOPA) is a commonly used PET tracer for the detection and staging of neuroendocrine tumors. In neuroendocrine tumors, [18F]FDOPA is decarboxylated to [18F]dopamine via the enzyme amino acid decarboxylase (AADC), leading to increased uptake when there is increased AADC activity. Recently, in our hospital, a new GMP compliant multi-dose production of [18F]FDOPA has been developed, [18F]FDOPA-H, resulting in a higher activity yield, improved molar activity and a lower administered mass than the conventional method ([18F]FDOPA-L). Aims: This study aimed to investigate whether the difference in molar activity affects the [18F]FDOPA uptake at physiological sites and in tumor lesions, in patients with NET. It was anticipated that the specific uptake of [18F]FDOPA-H would be equal to or higher than [18F]FDOPA-L. Methods: We retrospectively analyzed 49 patients with pathologically confirmed NETs and stable disease who underwent PET scanning using both [18F]FDOPA-H and [18F]FDOPA-L within a time span of 5 years. A total of 98 [18F]FDOPA scans (49 [18F]FDOPA-L and 49 [18F]FDOPA-H with average molar activities of 8 and 107 GBq/mmol) were analyzed. The SUVmean was calculated for physiological organ uptake and SUVmax for tumor lesions in both groups for comparison, and separately in subjects with low tumor load (1–2 lesions) and higher tumor load (3–10 lesions). Results: Comparable or slightly higher uptake was demonstrated in various physiological uptake sites in subjects scanned with [18F]FDOPA-H compared to [18F]FDOPA-L, with large overlap being present in the interquartile ranges. Tumor uptake was slightly higher in the [18F]FDOPA-H group with 3–10 lesion (SUVmax 6.83 vs. 5.19, p < 0.001). In the other groups, no significant differences were seen between H and L. Conclusion: [18F]FDOPA-H provides a higher activity yield, offering the possibility to scan more patients with one single production. Minor differences were observed in SUV's, with slight increases in uptake of [18F]FDOPA-H in comparison to [18F]FDOPA-L. This finding is not a concern for clinical practice, but could be of importance when quantifying follow-up scans while introducing new production methods with a higher molar activity of [18F]FDOPA. [ABSTRACT FROM AUTHOR]

Purpose: Metabolically active tumour volume (MATV) is a potential quantitative positron emission tomography (PET) imaging biomarker in melanoma. Accumulating data indicate that low MATV may predict increased chance of response to immunotherapy and overall survival. However, metastatic melanoma can present with numerous (small) tumour lesions, making manual tumour segmentation time-consuming. The aim of this study was to evaluate multiple semi-automatic segmentation workflows to determine reliability and reproducibility of MATV measurements in patients with metastatic melanoma. Methods: An existing cohort of 64 adult patients with histologically proven metastatic melanoma was used in this study. 18F-FDG PET/CT diagnostic baseline images were acquired using a European Association of Nuclear Medicine (EANM) Research Limited–accredited Siemens Biograph mCT PET/CT system (Siemens Healthineers, Knoxville, USA). PET data were analysed using manual, gradient-based segmentation and five different semi-automatic methods: three direct PET image–derived delineations (41MAX, A50P and SUV40) and two based on a majority-vote approach (MV2 and MV3), without and with (suffix '+') manual lesion addition. Correlation between the different segmentation methods and their respective associations with overall survival was assessed. Results: Correlation between the MATVs derived by the manual segmentation and semi-automated tumour segmentations ranged from R2 = 0.41 for A50P to R2 = 0.85 for SUV40+ and MV2+, respectively. Manual MATV segmentation did not differ significantly from the semi-automatic methods SUV40 (∆MATV mean ± SD 0.08 ± 0.60 mL, P = 0.303), SUV40+ (∆MATV − 0.10 ± 0.51 mL, P = 0.126), MV2+ (∆MATV − 0.09 ± 0.62 mL, P = 0.252) and MV3+ (∆MATV − 0.03 ± 0.55 mL, P = 0.615). Log-rank tests showed statistically significant overall survival differences between above and below median MATV patients for all segmentation methods with areas under the ROC curves of 0.806 for manual segmentation and between 0.756 [41MAX] and 0.807 [MV3+] for semi-automatic segmentations. Conclusions: Simple and fast semi-automated FDG PET segmentation workflows yield accurate and reproducible MATV measurements that correlate well with manual segmentation in metastatic melanoma. The most readily applicable and user-friendly SUV40 method allows feasible MATV measurement in prospective multicentre studies required for validation of this potential PET imaging biomarker for clinical use. [ABSTRACT FROM AUTHOR]

Background/aim: PET with 6-[18F]fluor-l-3,4-dihydroxyphenylalanine (18F-FDOPA) has been shown to be a useful imaging tool with a high sensitivity for the visualization of neuroendocrine tumors (NETs). 18F-FDOPA uptake in tumors other than NETs has been suggested previously, but data on this phenomenon are limited. We therefore studied the non-physiological, false-positive uptake of 18F-FDOPA in a large population of patients with a NET or with a high clinical suspicion of harboring a NET. Patients and methods: Retrospective single-center study among adult patients in whom 18F-FDOPA PET scintigraphy was performed between January 2004 and December 2014. The original scan report was compared with the original pathology report corresponding with the 18F-FDOPA PET-positive lesion. In case this was inconsistent with the diagnosis of a NET, both the scan and the pathology slides were reassessed. Specimens of these non-NET tissues were immunohistochemically stained for AADC. Results: 1070 18F-FDOPA PET scans from 705 patients were evaluated. Focal or multiple 18F-FDOPA-avid lesions were described in 709 18F-FDOPA PET scans (66%). Histology of these 18F-FDOPA PET-positive lesions was present in 508 (72%) cases. In seven cases, the histopathology was not compatible with NET but showed squamous cell carcinoma of the cervix, multiple myeloma (two cases), hepatocellular carcinoma, Schwannoma, adrenocortical carcinoma and a skeletal myxoid chondrosarcoma, with positive immunohistochemical staining for AADC in 67%. Conclusions: Pathological uptake of 18F-FDOPA does not always indicate the presence of a NET. The possibility of 18F-FDOPA uptake by tumor types other than NETs, although rare, should be considered. [ABSTRACT FROM AUTHOR]

Background: Surgery and high-dose radioactive iodine (131I) treatment are the cornerstones in the treatment of differentiated thyroid cancer. Patients without 131I uptake on the post-therapeutic whole body scan (WBS), but with detectable thyroglobulin (Tg) during thyroxine withdrawal (Tg-off), are evaluated with an 18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for tumor localization within three months. The yield of 18F-FDG-PET imaging and clinical usefulness of a Tg-off cutoff value to predict a positive scan were assessed. Methods: From 2002 to 2011, 52 patients with a negative WBS and concurrent detectable Tg-off were evaluated. Thirty-five PET scans were performed during initial treatment, 17 after recurrent disease. Thirty-two patients were on substitution therapy, 17 were evaluated with endogenous thyrotropin elevation, and 3 after recombinant human thyrotropin stimulation. To determine the Tg-off cutoff value, a receiver operating characteristic curve was used. Results: Nine (17%) 18F-FDG-PET scans were true positive, 3 (6%) false positive, 36 (69%) true negative, and 4 (8%) false negative (sensitivity 69%, specificity 92%). In 13%, a true-positive scan resulted in a change in the clinical management. The area under the receiver operating characteristic curve is 0.82 [CI 0.64-0.99] ( p<0.01), and the Tg-off cutoff value is 38.00 ng/mL (sensitivity 67%, specificity 95%). Ninety percent of 18F-FDG-PET true-positive patients had a Tg-off >2.00 ng/mL. Conclusions: An 18F-FDG-PET within three months after a negative WBS with detectable Tg-off showed additional tumor localization in 17% of the patients, leading to a change in clinical management in 13%. A clinically useful Tg-off cutoff value was not found, but 90% of positive 18F-FDG-PET scans occurred in patients with a Tg-off >2.00 ng/mL. [ABSTRACT FROM AUTHOR]

Purpose: Positron emission tomography (PET) using 6-[F]fluoro- L-dihydroxyphenylalanine (F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Methods: Seventy-seven consecutive carcinoid patients who underwent an F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. Results: All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. F-dopa PET detected 979 lesions. SUV on F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin ( r = 0.51) and urinary and plasma 5-HIAA ( r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Conclusion: Tumour load per patient measured with F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Carcinoid patients frequently develop a second primary malignancy (SPM), which can deserve full treatment. Distinguishing a SPM from carcinoid lesions is therefore important. Differentiation can be achieved using the difference in uptake between different positron emission tomography (PET) tracers. Methods and results: Between January 2005 and August 2008, 105 carcinoid patients were seen at the Department of Medical Oncology for treatment and follow-up. We identified 3 patients who presented with a new SPM in whom differentiation between carcinoid lesions and the SPM was guided by functional imaging of the catecholamine pathway with 6-fluoro-[18F]l-dihydroxyphenylalanine (18F-DOPA) PET and [18F]fluoro-2-deoxy-d-glucose (18F-FDG) PET as radiotracer for the glucose metabolism. All 3 patients had metastatic carcinoid disease and localised adenocarcinoma based on the PET-scans. For the adenocarcinoma they received curative treatment. Conclusion: The difference in uptake between these PET techniques can be used for decision making when a primary or metastatic SPM is suspected. [Copyright &y& Elsevier]

A letter to the editor is presented about the use of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in monitoring response to sorafenib treatment in patients with hepatocellular carcinoma.

Purpose: To evaluate the optimal tracer uptake time, the minimal amount of radioactivity and the inter-observer agreement for 11C-choline positron emission tomography/computed tomography (PET/CT) in patients with primary hyperparathyroidism (pHPT). Methods: Twenty-one patients with biochemically proven pHPT were retrospectively studied after injection of 6.3 ± 1.2 MBq/kg 11C-choline. PET data of the first nine patients, scanned for up to 60 min, were reconstructed in 10-min frames from 10- to 60-min postinjection (p.i.), mimicking varying 11C-choline uptake times. Parathyroid adenoma to background contrast ratios were calculated and compared, using standardized uptake values (SUVs). Data was reconstructed with varying scan durations (1, 2.5, 5, and 10 min) at 20–30-min p.i. (established optimal uptake time), mimicking less administered radioactivity. To establish the minimal required radioactivity, the SUVs in the shorter scan durations (1, 2.5, and 5 min) were compared to the 10-min scan duration to determine whether increased variability and/or statistical differences were observed. Four observers analyzed the 11C-choline PET/CT in four randomized rounds for all patients. Results: SUVpeak of the adenoma decreased from 30 to 40 p.i. onwards. All adenoma/background contrast ratios did not differ from 20- to 30-min p.i. onwards. The SUVs of adenoma in the scan duration of 1, 2.5, and 5 min all differed significantly from the same SUV in the 10-min scan duration (all p = 0.012). However, the difference in absolute SUV adenoma values was well below 10% and therefore not considered clinically significant. The inter-observer analysis showed that the Fleiss' kappa of the 1-min scan were classified as "moderate," while these values were classified as "good" in the 2.5-, 5-, and 10-min scan duration. Observers scored lower certainty scores in the 1- and 2.5-min scans compared to the 5- and 10-min scan durations. Conclusion: The optimal time to start PET/CT scanning in patients with pHPT is 20 min after mean injection of 6.3 MBq/kg 11C-choline, with a recommended scan duration of at least 5 min. Alternatively, the radioactivity dose can be lowered by 50% while keeping a 10-min scan duration without losing the accuracy of 11C-choline PET/CT interpretation. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: A feasibility study was performed to investigate the presence of VEGF in melanoma lesions by VEGF-SPECT with 111In-bevacizumab. In addition the effect of a single therapeutic bevacizumab dose on 111In-bevacizumab uptake was compared with VEGF levels in resected melanoma lesions. Patients and methods: Eligible were patients with stage III/IV melanoma who presented with nodal recurrent disease. VEGF-SPECT was performed after administration of 100 Mbq 111In-bevacizumab (8mg) at days 0, 2, 4 and 7 post injection. Tumour visualisation and quantification were compared with CT and FDG-PET. On day 7 a single dose of 7.5mg/kg bevacizumab was administered intravenously. On day 21, a second tracer dose 111In-bevacizumab was administered and scans were obtained on days 21, 25 and 28. Metastases were surgically resected within 2weeks after the last VEGF-SPECT scan and immunohistological (IHC) VEGF tumour expression was compared with 111In-bevacizumab tumour uptake. Results: Nine patients were included. FDG-PET and CT detected both in total 12 nodal lesions which were all visualised by VEGF-SPECT. At baseline, 111In-bevacizumab tumour uptake varied 3-fold between and 1.6±0.1-fold within patients. After a therapeutic dose of bevacizumab there was a 21±4% reduction in 111In-bevacizumab uptake. The 111In-bevacizumab tumour uptake in the second series positively correlated with the VEGF-A expression in the resected tumour lesions. Conclusion: VEGF-SPECT could visualise all known melanoma lesions. A single dose of bevacizumab slightly lowered 111In-bevacizumab uptake. Future studies should elucidate the role of VEGF-SPECT in the selection of patients and the individual dosing of bevacizumab treatment. [Copyright &y& Elsevier]