PET Image Acquisition Research Articles

Whole-Body Multiparametric PET in Clinical Oncology: Current Status, Challenges, and Opportunities.

The interpretation of clinical oncologic PET studies has historically used static reconstructions based on SUVs. SUVs and SUV-based images have important limitations, including dependence on uptake times and reduced conspicuity of tracer-avid lesions in organs with high background uptake. The acquisition of dynamic PET images enables additional PET reconstructions via Patlak modeling, which assumes that a tracer is irreversibly trapped by tissues of interest. The resulting multiparametric PET images capture a tracer's net trapping rate (Ki) and apparent volume of distribution (VD), separating the contributions of bound and free tracer fractions to the PET signal captured in the SUV. Potential benefits of multiparametric PET include higher quantitative stability, superior lesion conspicuity, and greater accuracy for differentiating malignant and benign lesions. However, the imaging protocols necessary for multiparametric PET are inherently more complex and time-intensive, despite the recent introduction of automated or semiautomated scanner-based reconstruction packages. In this Review, we examine the current state of multiparametric PET in whole-body oncologic imaging. We summarize the Patlak methodology and relevant tracer kinetics, discuss clinical workflows and protocol considerations, and highlight clinical challenges and opportunities. We aim to help oncologic imagers make informed decisions about whether to implement multiparametric PET in their clinical practices.

State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms.

Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.

Application of the Lugano Classification for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The PRoLoG Consensus Initiative (Part 2-Technical).

The aim of this initiative was to provide consensus recommendations from a consortium of academic and industry experts in the field of lymphoma and imaging for the consistent application of imaging assessment with the Lugano classification. Methods: Consensus was obtained through a series of meetings from July 2019 to October 2021 sponsored by the PINTaD (Pharma Imaging Network for Therapeutics and Diagnostics) as part of the ProLoG (PINTaD RespOnse criteria in Lymphoma wOrking Group) consensus initiative. Results: Consensus recommendations encompass all technical imaging aspects of the Lugano classification. Some technical considerations for PET/CT and diagnostic CT are clarified with regards to required imaging series and scan visits, as well as acquisition and reconstruction of PET images and influence of lesion size and background activity. Recommendations are given on the role of imaging and clinical reviewers as well as on training and monitoring. Finally, an example template of an imaging case report form is provided to support efficient collection of data with Lugano Classification. Conclusion: Consensus recommendations are made to comprehensively address technical and imaging areas of inconsistency and ambiguity in the classification encountered by end users. Such guidance should be used to support standardized acquisition and evaluation with the Lugano 2014.

Artificial intelligence-based PET image acquisition and reconstruction

Artificial intelligence-based PET image acquisition and reconstruction

Reducing Radiation Exposure from PET Patients.

This study measured the typical emitted radiation rate from the urinary bladder of PET patients after their scan and investigated simple methods for reducing the emitted radiation before discharge. Methods: The study included 83 patients (63 18F-FDG and 20 18F-NaF patients). Emitted radiation from the patients' urinary bladder was measured with an ionization survey meter at a 1-m distance, presuming the urinary bladder to be the primary source of radiation. The measurements were taken at different time points after PET image acquisition: immediate (prevoid 1), voided (postvoid 1), after waiting 30 min in the uptake room while drinking 500 mL of water (prevoid 2), and voided again (postvoid 2). Results: For 18F-FDG patients, the reduction of emitted radiation due to drinking water and voiding alone from prevoid 1 to decay-corrected postvoid 2 was an average of 22.49% ± 7.48% (13.65 ± 3.42 μSv/h to 10.48 ± 2.37 μSv/h, P < 0.001). For 18F-NaF patients, the reduction was an average of 25.80% ± 10.03% (9.83 ± 2.01 μSv/h to 7.23 ± 1.49 μSv/h, P < 0.001). Conclusion: In addition to the physical decay of the radiotracers, using the biologic clearance properties resulted in a significant decrease of the emitted radiation in this study. Implementing additional water consumption to facilitate voiding with 30 min of wait time before discharging certain 18F-FDG and 18F-NaF patients who need to be in close contact with others, such as elderly, caregivers, and inpatients, might facilitate lowering their emitted radiation by an average of 22%-25% due to voiding, not counting in the physical decay that should add an additional 17% reduction.

Effect of metformin on 18F-fluorodeoxyglucose uptake and positron emission tomographic imaging.

Metformin is widely used to treat diabetes, but induces changes in glucose uptake in both normal organs and tumors. Here, we review the effects of metformin on the uptake of 18F-fludeoxyglucose (18F-FDG) in tissues and tumors, and its influence on 18F-FDG positron emission tomographic imaging (18F-FDG PET), as well as the mechanisms involved. This is an important issue, because metformin has diverse effects on tissue uptake of 18F-FDG, and this can affect the quality and interpretation of PET images. Metformin increases glucose uptake in the gastrointestinal tract, cerebral white matter, and the kidney, while regions of the cerebrum associated with memory show decreased glucose uptake, and the myocardium shows no change. Hepatocellular carcinoma and breast cancer show increased glucose uptake after metformin administration, while thyroid cancer shows decreased uptake, and colon and pancreatic cancers show no change. A high-energy diet increases 18F-FDG uptake, but this effect is blocked by metformin. Withdrawal of metformin 48 h before PET image acquisition is widely recommended. However, based on our review of the literature, we propose that the differentiation of metformin discontinuation could be reasonable. But future clinical trials are still needed to support our viewpoint.

A Guide to ComBat Harmonization of Imaging Biomarkers in Multicenter Studies.

The impact of PET image acquisition and reconstruction parameters on SUV measurements or radiomic feature values is widely documented. This scanner effect is detrimental to the design and validation of predictive or prognostic models and limits the use of large multicenter cohorts. To reduce the impact of this scanner effect, the ComBat method has been proposed and is now used in various contexts. The purpose of this article is to explain and illustrate the use of ComBat based on practical examples. We also give examples in which the ComBat assumptions are not met and, thus, in which ComBat should not be used.

Evaluation of [18F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies.

Tau aggregates represent a key pathologic feature of Alzheimer’s disease and other neurodegenerative diseases. Recently, PET probes have been developed for in vivo detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer’s disease tauopathies. The novel tau PET tracer, [18F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer’s disease and non-Alzheimer’s disease tauopathies. To assess the ability of [18F]PI-2620 to detect regional tau burden in non-Alzheimer’s disease tauopathies compared with Alzheimer’s disease, patients with progressive supranuclear palsy (n = 3), corticobasal syndrome (n = 2), corticobasal degeneration (n = 1) or Alzheimer’s disease (n = 8), and healthy controls (n = 7) were recruited. All participants underwent MRI, amyloid β assessment and [18F]PI-2620 PET (Image acquisition at 60–90 min post-injection). Cortical and subcortical tau accumulations were assessed by calculating standardized uptake value ratios using [18F]PI-2620 PET. For pathologic validation, tau pathology was assessed using tau immunohistochemistry and compared with [18F]PI-2620 retention in an autopsied case of corticobasal degeneration. In Alzheimer’s disease, focal retention of [18F]PI-2620 was evident in the temporal and parietal lobes, precuneus, and cingulate cortex. Standardized uptake value ratio analyses revealed that patients with non-Alzheimer’s disease tauopathies had elevated [18F]PI-2620 uptake only in the globus pallidus, as compared to patients with Alzheimer’s disease, but not healthy controls. A head-to-head comparison of [18F]PI-2620 and [18F]PM-PBB3, another tau PET probe for possibly visualizing the four-repeat tau pathogenesis in non-Alzheimer’s disease, revealed different retention patterns in one subject with progressive supranuclear palsy. Imaging-pathology correlation analysis of the autopsied patient with corticobasal degeneration revealed no significant correlation between [18F]PI-2620 retention in vivo. High [18F]PI-2620 uptake at 60–90 min post-injection in the globus pallidus may be a sign of neurodegeneration in four-repeat tauopathy, but not necessarily practical for diagnosis of non-Alzheimer’s disease tauopathies. Collectively, this tracer is a promising tool to detect Alzheimer’s disease-tau aggregation. However, late acquisition PET images of [18F]PI-2620 may have limited utility for reliable detection of four-repeat tauopathy because of lack of correlation between post-mortem tau pathology and different retention pattern than the non-Alzheimer’s disease-detectable tau radiotracer, [18F]PM-PBB3. A recent study reported that [18F]PI-2620 tracer kinetics curves in four-repeat tauopathies peak earlier (within 30 min) than Alzheimer’s disease; therefore, further studies are needed to determine appropriate PET acquisition times that depend on the respective interest regions and diseases.

Acquisition Protocols to Optimize 68Ga-DOTA-NOC Position Emission Tomography/Computer Tomography Image Quality Based on Patient Body Mass Index and Injected Dose

Background: The choice of 68Ga-DOTA-1-Nal3-octreotide (68Ga-DOTA-NOC) injected dose and Position emission tomography/computer tomography (PET/CT) acquisition time is still a challenge for obtaining consistently high-quality PET image. Objective: To determine the optimal acquisition protocols based on patient body mass index (BMI) and the injected dose per kilogram for 68Ga-DOTA-NOC PET/CT imaging. Patients and Methods: This was a retrospective analysis of 51 patients (21 males and 30 females) who underwent clinical 68Ga-DOTANOC PET/CT imaging from November 2016 to March 2018 in Nanjing first hospital, the average BMI of these patients was 23.18 ± 3.45 kg/m2 with injected dose of 39.55–110.11 MBq. The study population was classified into groups based on Chinese standard BMI and injected dose. PET image quality and acquisition time were evaluated by coefficient of variance (CV) in the liver slice. Results: (1) The CV significantly increased with increasing weight and BMI (r = 0.647, 0.483, all P &lt; 0.01), and significantly decreased with increasing injected dose per kilogram (r = 0 695, P &lt; 0.01). (2) The CV differed significantly among 4 BMI-based groups, except for normal-weight group versus overweight group and overweight group versus obese group (P &lt; 0.01), and the ratio of overweight group and obese group to normal weight group was approximately 1.1 and 1.2, respectively. Meanwhile, the CV had a significant statistical difference among 3 injected dose per kilogram groups (P &lt; 0.01), and the ratio of that for low dose group and high dose group to moderate dose group was approximately 1.2 and 0.8. Conclusion: The findings showed a feasibility of obtaining consistently high-quality PET image at low injected dose and shorter acquisition time. Estimation of optimal acquisition time and injected dose using CV is valid in improving PET image quality, which can provide reference for the establishment and promotion of 68Ga-DOTA-NOC imaging protocols in China.

Diagnostic performance of FDG PET in large vessel vasculitis

This mini-review aims to qualitatively analyze the diagnostic performance of FDG PET in patients with diagnosis or suspected large vessel vasculitis (LVV). The future perspectives of PET in this field are also described. A comprehensive computer literature search of case–control studies published in PubMed/MEDLINE database in the last 10 years and regarding the diagnostic performance of FDG PET in LVV was carried out. Patient preparation, FDG PET image acquisition, and interpretation criteria were analyzed with respect to the recent joint procedural recommendations in LVV. We have summarized the methodological aspects and the diagnostic performances of FDG PET in detecting LVV considering 15 articles published in the literature. The data confirm the good diagnostic performance of FDG PET in this setting, using both visual and semiquantitative analysis. However, some heterogeneity has been found in several methodological aspects, as well as in the results of the included studies. Overall, FDG PET has a good diagnostic performance for the detection of active disease in LVV. Future prospective studies, more consistent with the joint procedural recommendations in LVV, are needed to support the use of standardized procedures and reproducible criteria for defining the presence of LVV with FDG PET/CT. Hybrid imaging and novel radiopharmaceuticals, more specific than FDG, are the future of PET in this field.

Reducing Respiratory Motion-Induced Errors in PET and CT Using an Iterative Image-to-Image Reconstruction Algorithm

Respiratory motion may change SUVmax and SUVpeak in PET images and compromise target definition and treatment response assessment in radiation therapy. While 4D imaging techniques may help address these issues, the time required for 4D data acquisition, image reconstruction and administrative costs keep 3D PET imaging staying as the mainstream in clinical practice. The purpose of this study is to explore the potential of using 4DCT information to remove motion-induced errors in 3D PET/CT images. A novel iterative image-to-image (III) reconstruction algorithm was developed. Specifically, a motion-blurred PET image was considered as a weighted average of PET images acquired at different respiration phases. PET images at each phase were assumed to be deformed from a virtual reference image. Image-intensity-based B-Spline registrations were performed on 4DCT from the end-inhale to the other phases. Resultant deformation maps were used to establish a set of composition equations between the virtual reference image and the blurred PET image. A maximum likelihood estimation maximization (MLEM) algorithm was used to solve these equations. The solution of these equations was smoothed by minimizing total gradient variations before generating the virtual reference image. A 10-phase 4D dataset with the resolution of 3.64×3.64×3.24 for PET and1.37×1.37×2.15 for CT was acquired from a lung cancer patient and used to benchmark the computed results. Different from previous studies, the III-reconstruction was performed in the image space, so there is no any tracking device or sorting operation required during the PET image acquisition. For the blurred PET, III-reconstructed PET and PET0 (which is the 4D-PET at the end-inhale phase), their relative SUVpeak are 10.2, 12.7 and 12.8, and SUVmax are 9.2, 12.5 and 13.1. With PET0 taken as the baseline, the III-reconstruction reduced the motion-induced error from 20.3% to 0.8% for SUVpeak, and from 29.8% to 4.6% for SUVmax. The mean SUV difference between the III-reconstructed PET and PET0 was 1.8% in the tumor region, and 13.2% over the whole image domain. Large differences between the two PET images were located mainly in the chest wall where ribs were mis-registered about 6 mm due to discontinuous motion between the ribs and lungs. The III-reconstruction algorithm was also applied to the 4DCT image. Image contrast ratios for the blurred 3DCT, III-reconstructed CT, and CT0 are 1.8, 3.7 and 4.0, respectively. The III-reconstruction method can be used to correct motion-induced errors in SUVmax and SUVpeak and improve image contrasts in free-breathing PET and CT images. This method does not require sorting projection data, thereby reducing financing cost and clinical burden. Further investigation of this reconstruction method is warranted.

Influence of detectors efficiency normalization on small animal PET image quality

LabPET GE 4 (a small animal positron emission tomograph) image acquisition is done by 1536 independents channels. Differences in the rate counting of each channel must be corrected so as not compromise image quality. Equipment user manual recommends that normalization of the detectors efficiency be made as often as possible and always whenever there are hardware or software parameters changes - included, but not limited to channels parameters adjustments, electronic cards replacements, channels activation or inactivation or software update. This work evaluates the normalization effects on the image quality parameters. PET image acquisition were performed using recommended parameters by the NEMA NU 4-2008 standards. Image was reconstructed in different ways using different normalization files. The tests performed indicated that the image quality parameters do not vary significantly with different normalization data. Therefore, a daily routine of normalizations is not justified, suggesting a periodical frequency of one month or more for this procedure.

Effect of forced diuresis during 18F-DCFPyL PET/CT in patients with prostate cancer: activity in ureters, kidneys and bladder and occurrence of halo artefacts around kidneys and bladder.

Forced diuresis may improve readability of 2-(3-(1-carboxy-5-[(6-[F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (F-DCFPyL) PET/computed tomography (CT) by reducing focal ureteral activity. A total of 40 patients received furosemide simultaneously with F-DCFPyL (cohort 1) and 40 patients received furosemide 85 min after F-DCFPyL administration (cohort 2). The frequency of occurrence of activity depositions in ureters and halo artefacts near the kidneys and bladder was measured, as well as intensity of F-DCFPyL uptake in kidneys and bladder. At 120 min after injection of F-DCFPyL, a significantly lower number of F-DCFPyL depositions in ureters was found in cohort 2. Moreover, F-DCFPyL uptake in kidneys and bladder was significantly lower in this cohort; however, the occurrence of halo artefacts was similar in both groups. Administration of furosemide may improve interpretation of F-DCFPyL PET/CT as it results in less activity depositions in ureters. However, the effect depends on the timing of furosemide administration in relation to F-DCFPyL administration and PET/CT acquisition time. Acquisition of PET-images 120 min after F-DCFPyL administration benefits from late furosemide administration (85 min after injection).

Robust real-time extraction of respiratory signals from PET list-mode data

Respiratory motion, which typically cannot simply be suspended during PET image acquisition, affects lesions’ detection and quantitative accuracy inside or in close vicinity to the lungs. Some motion compensation techniques address this issue via pre-sorting (‘binning’) of the acquired PET data into a set of temporal gates, where each gate is assumed to be minimally affected by respiratory motion. Tracking respiratory motion is typically realized using dedicated hardware (e.g. using respiratory belts and digital cameras). Extracting respiratory signals directly from the acquired PET data simplifies the clinical workflow as it avoids handling additional signal measurement equipment. We introduce a new data-driven method ‘combined local motion detection’ (CLMD). It uses the time-of-flight (TOF) information provided by state-of-the-art PET scanners in order to enable real-time respiratory signal extraction without additional hardware resources.CLMD applies center-of-mass detection in overlapping regions based on simple back-positioned TOF event sets acquired in short time frames. Following a signal filtering and quality-based pre-selection step, the remaining extracted individual position information over time is then combined to generate a global respiratory signal. The method is evaluated using seven measured FDG studies from single and multiple scan positions of the thorax region, and it is compared to other software-based methods regarding quantitative accuracy and statistical noise stability.Correlation coefficients around 90% between the reference and the extracted signal have been found for those PET scans where motion affected features such as tumors or hot regions were present in the PET field-of-view. For PET scans with a quarter of typically applied radiotracer doses, the CLMD method still provides similar high correlation coefficients which indicates its robustness to noise. Each CLMD processing needed less than 0.4 s in total on a standard multi-core CPU and thus provides a robust and accurate approach enabling real-time processing capabilities using standard PC hardware.

Enhancement of multimodality texture-based prediction models via optimization of PET and MR image acquisition protocols: a proof of concept

Texture-based radiomic models constructed from medical images have the potential to support cancer treatment management via personalized assessment of tumour aggressiveness. While the identification of stable texture features under varying imaging settings is crucial for the translation of radiomics analysis into routine clinical practice, we hypothesize in this work that a complementary optimization of image acquisition parameters prior to texture feature extraction could enhance the predictive performance of texture-based radiomic models. As a proof of concept, we evaluated the possibility of enhancing a model constructed for the early prediction of lung metastases in soft-tissue sarcomas by optimizing PET and MR image acquisition protocols via computerized simulations of image acquisitions with varying parameters. Simulated PET images from 30 STS patients were acquired by varying the extent of axial data combined per slice (‘span’). Simulated T1-weighted and T2-weighted MR images were acquired by varying the repetition time and echo time in a spin-echo pulse sequence, respectively. We analyzed the impact of the variations of PET and MR image acquisition parameters on individual textures, and we investigated how these variations could enhance the global response and the predictive properties of a texture-based model. Our results suggest that it is feasible to identify an optimal set of image acquisition parameters to improve prediction performance. The model constructed with textures extracted from simulated images acquired with a standard clinical set of acquisition parameters reached an average AUC of in bootstrap testing experiments. In comparison, the model performance significantly increased using an optimal set of image acquisition parameters (), with an average AUC of . Ultimately, specific acquisition protocols optimized to generate superior radiomics measurements for a given clinical problem could be developed and standardized via dedicated computer simulations and thereafter validated using clinical scanners.

Early PET imaging with [68]Ga-PSMA-11 increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence.

PET/CT using 68Ga-labelled prostate-specific membrane antigen PSMA-11 (HBEDD-CC) has emerged as a promising imaging method in the diagnostic evaluation of prostate cancer (PC) patients with biochemical recurrence. However, assessment of local recurrence (LR) may be limited by intense physiologic tracer accumulation in the urinary bladder on whole-body scans, normally conducted 60min post-tracer injection (p.i.). It could be shown on early dynamic imaging studies that 68Ga-PSMA-11 uptake in PC lesions occurs earlier than tracer accumulation in the urinary bladder. This study aims to investigate whether early static PET acquisition increases detection rate of local recurrence on 68Ga-PSMA-11 PET/CT in comparison to PET imaging 60min p.i.. 203 consecutive PC patients with biochemical failure referred to 68Ga-PSMA-11 PET/CT were analysed retrospectively (median prostate specific antigen (PSA) value: 1.44ng/ml). In addition to whole-body PET/CT scans 60min p.i., early static imaging of the pelvis was performed, starting at a median time of 283s p.i. (range: 243-491s). Assessment was based on visual analysis and calculation of maximum standardized uptake value (SUVmax) of pathologic lesions present in the pelvic area found on early PET imaging and on 60min-PET scans. 26 patients (12.8%) were judged positive for LR on PET scans 60min p.i. (median SUVmax: 10.8; range: 4.7-40.9), whereas 50 patients (24.6%) revealed a lesion suggestive of LR on early PET imaging (median SUVmax: 5.9; range: 2.9-17.6), resulting in a significant rise in detection rate (p<0.001). Equivocal findings on PET scans 60min p.i. decreased significantly with the help of early imaging (15.8% vs. 4.5% of patients; p<0.001). Tracer activity in the urinary bladder with a median SUVmax of 8.2 was present in 63 patients on early PET scans (31.0%). However, acquisition starting time of early PET scans differed significantly in the patient groups with and without urinary bladder activity (median starting time of 321 vs. 275s p.i.; range: 281-491 vs. 243-311s p.i.; p<0.001). Median SUVmax value of lesions suggestive of LR on early images was significantly higher in comparison to gluteal muscle, inguinal vessels and seminal vesicle/anastomosis (median SUVmax: 5.9 vs. 1.9, 4.0 and 2.4, respectively). Performance of early imaging in 68Ga-PSMA-11 PET/CT in addition to whole-body scans 60min p.i. increases the detection rate of local recurrence in PC patients with biochemical recurrence. Acquisition of early PET images should be started as early as 5min p.i. in order to avoid disturbing tracer activity in the urinary bladder occuring at a later time point.

Sign determination methods for the respiratory signal in data-driven PET gating

Patient respiratory motion during PET image acquisition leads to blurring in the reconstructed images and may cause significant artifacts, resulting in decreased lesion detectability, inaccurate standard uptake value calculation and incorrect treatment planning in radiation therapy. To reduce these effects data can be regrouped into (nearly) ‘motion-free’ gates prior to reconstruction by selecting the events with respect to the breathing phase. This gating procedure therefore needs a respiratory signal: on current scanners it is obtained from an external device, whereas with data driven (DD) methods it can be directly obtained from the raw PET data. DD methods thus eliminate the use of external equipment, which is often expensive, needs prior setup and can cause patient discomfort, and they could also potentially provide increased fidelity to the internal movement. DD methods have been recently applied on PET data showing promising results. However, many methods provide signals whose direction with respect to the physical motion is uncertain (i.e. their sign is arbitrary), therefore a maximum in the signal could refer either to the end-inspiration or end-expiration phase, possibly causing inaccurate motion correction. In this work we propose two novel methods, CorrWeights and CorrSino, to detect the correct direction of the motion represented by the DD signal, that is obtained by applying principal component analysis (PCA) on the acquired data. They only require the PET raw data, and they rely on the assumption that one of the major causes of change in the acquired data related to the chest is respiratory motion in the axial direction, that generates a cranio-caudal motion of the internal organs. We also implemented two versions of a published registration-based method, that require image reconstruction. The methods were first applied on XCAT simulations, and later evaluated on cancer patient datasets monitored by the Varian Real-time Position ManagementTM (RPM) device, selecting the lower chest bed positions. For each patient different time intervals were evaluated ranging from 50 to 300 s in duration. The novel methods proved to be generally more accurate than the registration-based ones in detecting the correct sign of the respiratory signal, and their failure rates are lower than 3% when the DD signal is highly correlated with the RPM. They also have the advantage of faster computation time, avoiding reconstruction. Moreover, CorrWeights is not specifically related to PCA and considering its simple implementation, it could easily be applied together with any DD method in clinical practice.

Fluorine-18 fluorocholine PET-CT localizes hyperparathyroidism in patients with inconclusive conventional imaging: a multicenter study from the Netherlands.

Several reports have shown good performance of fluorine-18 fluorocholine (F-FCH) PET-computed tomography (CT) for parathyroid localization, although overall evidence remains scarce. We collected data from three institutions in the Netherlands and investigated the performance of F-FCH PET-CT as a second-line imaging modality. We performed a retrospective review of all patients at least 18 years who underwent F-FCH PET-CT for biochemically proven hyperparathyroidism (HPT) and inconclusive ultrasound and sestamibi scintigraphy. Acquisition of PET images was performed 30 min after the administration of 2 MBq/kg F-FCH, together with a low-dose CT. PET-CT scans were performed in 33 (75%) women and 11 (25%) men with a mean age of 58.9 (range 31-80 years). Three patients had multiple endocrine neoplasia type 1, one patient had tertiary HPT because of Alport syndrome and the remaining patients had sporadic primary HPT. F-FCH PET-CT was positive in 34/44 (77.3%) cases. Of the 35 abnormal glands resected in 33 patients, F-FCH PET-CT could successfully localize 33/35 (94.3%), with only one false-positive result [positive predictive value (PPV)=97.1%]. Comparison of the 10 patients with negative PET-CT with the 34 patients with positive PET-CT showed no significant differences in age, sex, ratio of preoperative calcium, use of cinacalcet, history of neck surgery, and concomitant multinodular goiter. Our study shows excellent performance of F-FCH PET-CT in patients with HPT and inconclusive conventional imaging. Because of its favorable characteristics with high performance, prospective studies should be initiated to determine whether this new technique may replace conventional sestamibi scintigraphy as a first-line imaging modality.

Emerging clinical applications for PET/MR in the field of cardiovascular imaging

In the same way in which PET/CT has been shown to be a powerful multimodality imaging tool, there are compelling reasons for combining PET and MRI. Combined PET-MRI systems, i.e. the simultaneous acquisition of PET and MR images, combine the most sensitive and robust noninvasive clinical technology for molecular imaging (PET) with high-contrast, high-resolution and time-resolved MR imaging. The fusion of these two modalities into one acquisition system has represented a clear breakthrough in the imaging field, and the implementation of these imaging systems for clinical applications still remains a challenge. However, a certain number of pitfalls still remain and must be avoided. In this review, we will first discuss the technological advancements, which take advantage of simultaneous PET and MR acquisitions, such as improved attenuation and motion correction, but also the remaining issues, which must be considered when performing this combined imaging. Second, we will present the first clinical applications of PET-MRI emerging in the field of cardiac imaging. Lastly, we will review promising future clinical applications for PET-MRI in the vascular field.

(R)-NODAGA-PSMA: A Versatile Precursor for Radiometal Labeling and Nuclear Imaging of PSMA-Positive Tumors.

PurposeThe present study aims at developing and evaluating an urea-based prostate specific membrane antigen (PSMA) inhibitor suitable for labeling with 111In for SPECT and intraoperative applications as well as 68Ga and 64Cu for PET imaging.MethodsThe PSMA-based inhibitor-lysine-urea-glutamate-coupled to the spacer Phe-Phe-D-Lys(suberoyl) and functionalized with the enantiomerically pure prochelator (R)-1-(1-carboxy-3-carbotertbutoxypropyl)-4,7-carbotartbutoxymethyl)-1,4,7-triazacyclononane ((R)-NODAGA(tBu)3), to obtain (R)-NODAGA-Phe-Phe-D-Lys(suberoyl)-Lys-urea-Glu (CC34). CC34 was labeled with 111In, 68Ga and 64Cu. The radioconjugates were further evaluated in vitro and in vivo in LNCaP xenografts by biodistribution and PET studies. Biodistribution studies were also performed with 68Ga-HBED-CC-PSMA (HBED-CC: N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid) and 111In-PSMA-617 for comparison.Results 68Ga-CC34, 64Cu-CC34, and 111In-CC34 were prepared in radiochemical purity >95%. 68/natGa-CC34, 64/natCu-CC34, 111/natIn-CC34, 68/natGa-HBED-CC-PSMA, and 111/natIn-PSMA-617 exhibited high affinity for the LNCaP cells, with Kd values of 19.3±2.5 nM, 27.5±2.7 nM, 5.5±0.9 nM, 2.9±0.6 nM and 5.4±0.8 nM, respectively. They revealed comparable internalization profiles with approximately 75% of the total cell associated activity internalized after 3 h of incubation. 68Ga-CC34 showed very high stability after its administration in mice. Tumor uptake of 68Ga-CC34 (14.5±2.9% IA/g) in LNCaP xenografts at 1 h p.i. was comparable to 68Ga-HBED-CC-PSMA (15.8±1.4% IA/g) (P = 0.67). The tumor-to-normal tissue ratios at 1 and 2 h p.i of 68Ga-CC34 were also comparable to 68Ga-HBED-CC-PSMA (P>0.05). Tumor uptake of 111In-CC34 (28.5±2.6% IA/g) at 1 h p.i. was lower than 111In-PSMA-617 (52.1±6.5% IA/g) (P = 0.02). The acquisition of PET-images with 64Cu-CC34 at later time points showed wash-out from the kidneys, while tumor uptake still remained relatively high. This resulted in an increased tumor-to-kidney ratio over time.Conclusions 68Ga-CC34 is comparable to 68Ga-HBED-CC-PSMA in terms of tumor uptake and tumor to normal tissue ratios. 64Cu-CC34 could enable high contrast imaging of PSMA positive tissues characterized by elevated expression of PSMA or when delayed imaging is required. 64Cu-CC34 is currently being prepared for clinical translation.