Positron Emission Tomography In Oncology Research Articles

Development of the quantitative PET prostate phantom (Q3P) for improved quality assurance of 18F-PSMA PET imaging in metastatic prostate cancer.

Phantoms are commonly used to evaluate and compare the performance of imaging systems given the known ground truth. Positron emission tomography (PET) scanners are routinely validated using the NEMA image quality phantom, in which lesions are modeled using 10 to 37mm fillable spheres. The NEMA phantom neglects, however, to model focal (3-10-mm), high-uptake lesions that are increasingly observed in prostate-specific membrane antigen (PSMA) PET images. PSMA-targeting radiopharmaceuticals allow for enhanced detection of metastatic prostate cancers. As such, there is significant need to develop an updated phantom which considers both the quantitative and lesion detectability of this new paradigm in oncological PET imaging. In this work, we present the Quantitative PET Prostate Phantom (Q3P); a portable and modular phantom that can be used to improve and harmonize imaging protocols for 18F-PSMA PET scans. A one-piece cylindrical phantom was designed effectively in two halves, which we call modules. Module 1 was designed to mimic lesions in the presence of background, and Module 2 mimicked very high contrast conditions (i.e., very low background) that can be observed in 18F-PSMA PET scans. Shell-less radioactive spheres (3-16-mm) were cast using epoxy resin mixed with sodium-22 (22Na), a long half-life positron emitter with positron range similar to 18F. To establish realistic lesion contrast, the 22Na spheres were mounted in a cylindrical chamber that can be filled with an 18F background (module 1). Thirteen exchangeable spherical cavity inserts (3-37-mm) were machined in two parts and solvent welded together, and filled with 18F (50 kBq/mL) to model lesions with very high contrast (module 2). Five 2.5-min PET scans were acquired on a 5-ring GE Discovery MI PET/CT scanner (General Electric, USA). Lesions were segmented using 41% of SUVmax fixed thresholding (41% FT) and recovery coefficients (RCs) were computed from 5 noise realizations. The manufactured phantom is portable (5.7kg) and scan preparation takes less than 40min. The total 22Na activity is 250 kBq, allowing it to be shipped as an exempt package under International Atomic Energy Agency (IAEA) regulations. Recovery coefficients, computed using PSF modeling and no post-reconstruction smoothing, were 130.3% (16mm), 147.1% (10mm), 87.2% (6mm), and 7.0% (3mm) for RCmax, which decreased to 91.1% (16mm), 90.6% (10mm), 53.2% (6mm), and 3.6% (3mm) for RCmean in the 22Na spheres. Comparatively, 18F sphere recovery was 110.7% (17mm), 123.6% (10mm), 106.5% (7mm), and 23.3% (3mm) for RCmax, which was reduced to 76.7% (17mm), 77.7% (10mm), 66.8% (7mm), and 13.5% (3mm), for RCmean. A standardized imaging phantom was developed for lesion quantification assessment in 18F-PSMA PET images. The phantom is configurable, providing users with the opportunity to modify background activity levels or sphere sizes according to clinical demands. Distributed to the community, the Q3P phantom has the potential to enable better assessment of lesion quantification and harmonization of 18F-PSMA PET imaging, which may lead to more robust predictive metrics and better outcome prediction in metastatic prostate cancer.

Physiological myocardial 18F-FDG uptake pattern in oncologic PET/CT: comparison with findings in cardiac sarcoidosis.

Physiological myocardial 18F-fluorodeoxyglucose (18F-FDG) uptake in oncologic positron emission tomography (PET)/computed tomography (CT) is commonly observed with multiple variations under clinical fasting conditions. The purpose of the present study was to evaluate physiological myocardial 18F-FDG uptake pattern by comparing with the results in cardiac sarcoidosis. A total of 174 examinations in 174 patients without cardiac disease and 27 examinations in 17 patients with cardiac sarcoidosis were performed. The polar map images generated from 18F-FDG PET/CT data were visually assessed as "basal-ring," "focal," and "focal on diffuse" patterns. Semi-quantitative analysis was also performed using the regional relative 18F-FDG uptake (% uptake). On visual analysis, the "focal on diffuse" pattern was the most common in both examinations (43% and 59%, respectively). The physiological % uptake in the lateral and basal septal walls tended to be higher. Subgroup analysis showed significantly higher uptake in the mid-wall and left circumflex territory. In cardiac sarcoidosis patients, there was a significant difference only between segments 2 and 15 (p=0.04). No significant differences were observed between the base-mid-apical territory and coronary artery branch territory. High 18F-FDG uptake in the basal septal walls is likely to be observed as both physiological uptake in patients without cardiac disease and pathological uptake in patients with cardiac sarcoidosis.

Need for objective task-based evaluation of AI-based segmentation methods for quantitative PET.

Artificial intelligence (AI)-based methods are showing substantial promise in segmenting oncologic positron emission tomography (PET) images. For clinical translation of these methods, assessing their performance on clinically relevant tasks is important. However, these methods are typically evaluated using metrics that may not correlate with the task performance. One such widely used metric is the Dice score, a figure of merit that measures the spatial overlap between the estimated segmentation and a reference standard (e.g., manual segmentation). In this work, we investigated whether evaluating AI-based segmentation methods using Dice scores yields a similar interpretation as evaluation on the clinical tasks of quantifying metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumor from PET images of patients with non-small cell lung cancer. The investigation was conducted via a retrospective analysis with the ECOG-ACRIN 6668/RTOG 0235 multi-center clinical trial data. Specifically, we evaluated different structures of a commonly used AI-based segmentation method using both Dice scores and the accuracy in quantifying MTV/TLG. Our results show that evaluation using Dice scores can lead to findings that are inconsistent with evaluation using the task-based figure of merit. Thus, our study motivates the need for objective task-based evaluation of AI-based segmentation methods for quantitative PET.

Observer-study-based approaches to quantitatively evaluate the realism of synthetic medical images

Objective. Synthetic images generated by simulation studies have a well-recognized role in developing and evaluating imaging systems and methods. However, for clinically relevant development and evaluation, the synthetic images must be clinically realistic and, ideally, have the same distribution as that of clinical images. Thus, mechanisms that can quantitatively evaluate this clinical realism and, ideally, the similarity in distributions of the real and synthetic images, are much needed. Approach. We investigated two observer-study-based approaches to quantitatively evaluate the clinical realism of synthetic images. In the first approach, we presented a theoretical formalism for the use of an ideal-observer study to quantitatively evaluate the similarity in distributions between the real and synthetic images. This theoretical formalism provides a direct relationship between the area under the receiver operating characteristic curve, AUC, for an ideal observer and the distributions of real and synthetic images. The second approach is based on the use of expert-human-observer studies to quantitatively evaluate the realism of synthetic images. In this approach, we developed a web-based software to conduct two-alternative forced-choice (2-AFC) experiments with expert human observers. The usability of this software was evaluated by conducting a system usability scale (SUS) survey with seven expert human readers and five observer-study designers. Further, we demonstrated the application of this software to evaluate a stochastic and physics-based image-synthesis technique for oncologic positron emission tomography (PET). In this evaluation, the 2-AFC study with our software was performed by six expert human readers, who were highly experienced in reading PET scans, with years of expertise ranging from 7 to 40 years (median: 12 years, average: 20.4 years). Main results. In the ideal-observer-study-based approach, we theoretically demonstrated that the AUC for an ideal observer can be expressed, to an excellent approximation, by the Bhattacharyya distance between the distributions of the real and synthetic images. This relationship shows that a decrease in the ideal-observer AUC indicates a decrease in the distance between the two image distributions. Moreover, a lower bound of ideal-observer AUC = 0.5 implies that the distributions of synthetic and real images exactly match. For the expert-human-observer-study-based approach, our software for performing the 2-AFC experiments is available at https://apps.mir.wustl.edu/twoafc. Results from the SUS survey demonstrate that the web application is very user friendly and accessible. As a secondary finding, evaluation of a stochastic and physics-based PET image-synthesis technique using our software showed that expert human readers had limited ability to distinguish the real images from the synthetic images. Significance. This work addresses the important need for mechanisms to quantitatively evaluate the clinical realism of synthetic images. The mathematical treatment in this paper shows that quantifying the similarity in the distribution of real and synthetic images is theoretically possible by using an ideal-observer-study-based approach. Our developed software provides a platform for designing and performing 2-AFC experiments with human observers in a highly accessible, efficient, and secure manner. Additionally, our results on the evaluation of the stochastic and physics-based image-synthesis technique motivate the application of this technique to develop and evaluate a wide array of PET imaging methods.

Deep learning-based attenuation map generation with simultaneously reconstructed PET activity and attenuation and low-dose application

Objective. In PET/CT imaging, CT is used for positron emission tomography (PET) attenuation correction (AC). CT artifacts or misalignment between PET and CT can cause AC artifacts and quantification errors in PET. Simultaneous reconstruction (MLAA) of PET activity (λ-MLAA) and attenuation (μ-MLAA) maps was proposed to solve those issues using the time-of-flight PET raw data only. However, λ-MLAA still suffers from quantification error as compared to reconstruction using the gold-standard CT-based attenuation map (μ-CT). Recently, a deep learning (DL)-based framework was proposed to improve MLAA by predicting μ-DL from λ-MLAA and μ-MLAA using an image domain loss function (IM-loss). However, IM-loss does not directly measure the AC errors according to the PET attenuation physics. Our preliminary studies showed that an additional physics-based loss function can lead to more accurate PET AC. The main objective of this study is to optimize the attenuation map generation framework for clinical full-dose 18F-FDG studies. We also investigate the effectiveness of the optimized network on predicting attenuation maps for synthetic low-dose oncological PET studies. Approach. We optimized the proposed DL framework by applying different preprocessing steps and hyperparameter optimization, including patch size, weights of the loss terms and number of angles in the projection-domain loss term. The optimization was performed based on 100 skull-to-toe 18F-FDG PET/CT scans with minimal misalignment. The optimized framework was further evaluated on 85 clinical full-dose neck-to-thigh 18F-FDG cancer datasets as well as synthetic low-dose studies with only 10% of the full-dose raw data. Main results. Clinical evaluation of tumor quantification as well as physics-based figure-of-merit metric evaluation validated the promising performance of our proposed method. For both full-dose and low-dose studies, the proposed framework achieved <1% error in tumor standardized uptake value measures. Significance. It is of great clinical interest to achieve CT-less PET reconstruction, especially for low-dose PET studies.

Insidentaloma Pada 18f-FDG Pet

Whole-body imaging with Positron Emission Tomography (PET) using F-18 Fluorodeoxyglucose (18F-FDG) has been widely used along with the evaluation and clinical management of neoplasms. The main advantage of using whole-body imaging with 18F-FDG PET in oncology is the ability to detect unexpected or incidental tumor sites. The purpose of this study was to determine the incidentaloma of the 18F-FDG PET examination in nuclear medicine. This research uses the literature study method or literature review. The conclusion of this study is that PET/CT imaging can detect incidental primary tumors and pre-malignant lesions. FDG avidity and lesion morphology assessed by PET and CT images complement each other and help locate these lesions.

Breast Cancer and PET Imaging.

Breast cancer is the most common malignancy in women and among the most common indications of oncologic positron emission tomography (PET) studies. In this review article, updated anatomical, pathological, and clinical information about breast cancer were provided for Nuclear Medicine physicians to better understand breast cancer and interpret PET images and a review of the literature on the use of PET imaging in breast cancer was summarized.

Quantification of Myocardial Dosimetry and Glucose Metabolism Using a 17-Segment Model of the Left Ventricle in Esophageal Cancer Patients Receiving Radiotherapy.

ObjectivePrevious studies have shown that increased cardiac uptake of 18F-fluorodeoxyglucose (FDG) on positron emission tomography (PET) may be an indicator of myocardial injury after radiotherapy (RT). The primary objective of this study was to quantify cardiac subvolume dosimetry and 18F-FDG uptake on oncologic PET using a 17-segment model of the left ventricle (LV) and to identify dose limits related to changes in cardiac 18F-FDG uptake after RT.MethodsTwenty-four esophageal cancer (EC) patients who underwent consecutive oncologic 18F-FDG PET/CT scans at baseline and post-RT were enrolled in this study. The radiation dose and the 18F-FDG uptake were quantitatively analyzed based on a 17-segment model. The 18F-FDG uptake and doses to the basal, middle and apical regions, and the changes in the 18F-FDG uptake for different dose ranges were analyzed.ResultsA heterogeneous dose distribution was observed, and the basal region received a higher median mean dose (18.36 Gy) than the middle and apical regions (5.30 and 2.21 Gy, respectively). Segments 1, 2, 3, and 4 received the highest doses, all of which were greater than 10 Gy. Three patterns were observed for the myocardial 18F-FDG uptake in relation to the radiation dose before and after RT: an increase (5 patients), a decrease (13 patients), and no change (6 patients). In a pairing analysis, the 18F-FDG uptake after RT decreased by 28.93 and 12.12% in the low-dose segments (0–10 Gy and 10–20 Gy, respectively) and increased by 7.24% in the high-dose segments (20–30 Gy).ConclusionThe RT dose varies substantially within LV segments in patients receiving thoracic EC RT. Increased 18F-FDG uptake in the myocardium after RT was observed for doses above 20 Gy.

Biochemical basics of imaging in positron emission tomography in oncology. Part 3

This article provides an overview of the main literature data of biochemical basics and the clinical application of positron emission tomography, one of the promising technologies of radiation imaging in oncology.In the final part, the biokinetics of radiopharmaceuticals that display the proliferative activity of malignant cells and the degree of hypoxia in the tumor focus are examined in detail. The results of studies devoted to assessing their effectiveness, the main indications for their use, the features of preparation for the study, as well as promising scientific developments in this industry are presented.

Chemistry Considerations for the Clinical Translation of Oncology PET Radiopharmaceuticals.

Positron emission tomography (PET) has proven to be an invaluable tool in the staging and management of disease in oncology; however, [18F]fluorodeoxyglucose ([18F]FDG) remains the most widely used PET radiopharmaceutical despite the large financial investment in novel radiotracer development. We report our perspective and experience of translating radiopharmaceuticals into clinical studies, discussing the PET development pipeline from a chemistry perspective. We hope that, by identifying potential points of attrition along the pipeline and suggesting solutions to these problems, we may help others take their preclinical radiotracers into human studies. This review focuses primarily on the development of fluorine-18 radiopharmaceuticals, although the broader field of radiometal chemistry is considered where the translation journey is similar.

Biochemical basics of imaging in positron emission tomography in oncology. Part 2

This article provides an overview of the main literature data of biochemical basics and the clinical application of positron emission tomography, one of the promising technologies of radiation imaging in oncology. In the current part we discuss in detail the biokinetics of radiopharmaceuticals used to visualize various groups of tumor cells receptors. These include angiogenesis markers - RGD peptides, ligands for somatostatin receptors, agents for sex hormone imaging, ligands for prostate-specific membrane antigen and to activating EGFR mutant kinase. It contains results of studies that were dedicated to search for optimal modifications of these radiopharmaceuticals to increase diagnostic efficiency, their comparative analysis is carried out, the results of their use in cancer research and development prospects in this industry are highlighted.

Excitatory glutamate transporter EAAC1 as an important transporter of N-(2-[18F]fluoropropionyl)-L-glutamate in oncology PET imaging

IntroductionWe have reported that N-(2-[18F]fluoropropionyl)-L-glutamate ([18F]FPGLU) was a potential amino acid tracer for tumor imaging with positron emission tomography (PET). In this study, the relationship between glutamate transporter excitatory amino acid carrier 1 (EAAC1) expression and [18F]FPGLU uptake in rat C6 glioma cell lines and human SPC-A-1 lung adenocarcinoma cell lines was investigated. MethodsThe uptake of [18F]FPGLU was assessed in ATRA-treated and untreated C6 cell lines, and also in EAAC1 knock-down SPC-A-1(shRNA) cells and SPC-A-1(NT) control cells. PET imaging of [18F]FPGLU was performed on the SPC-A-1 and SPC-A-1 (shRNA)-bearing mice models. ResultsThe uptake of [18F]FPGLU in C6 cells increased significantly after induced by ATRA for 24, 48, and 72 h, which was closely related to expression of EAAC1 in C6 cells (R2 = 0.939). Compared with the SPC-A-1(NT) control cells, the uptake of [18F]FPGLU on EAAC1 knock-down SPC-A-1(shRNA) cells significantly decreased to 64.0%. Moreover, the uptake of [18F]FPGLU in EAAC1 knock-down SPC-A-1(shRNA) xenografts was significantly lower than that in SPC-A-1 xenografts, with tumor/muscle ratios of 3.01 vs. 1.67 at 60 min post-injection of [18F]FPGLU. ConclusionThe transport mechanism of [18F]FPGLU in glioma C6 and lung adenocarcinoma SPC-A-1 cell lines mainly involves in glutamate transporter EAAC1. EAAC1 is an important transporter of N-(2-[18F]fluoropropionyl)-L-glutamate in oncologic PET imaging.

Positron emission tomography in the pediatric oncology

The methodical features of using of the positron emission tomography with 18F-fluorodeoxyglucose in pediatric oncological patients and variations of normal distribution of radiopharmaceutical in children were revealed. Diagnostic efficacies of PET/CT in different pediatric malignancies were represented. It is showed that the modality is the important additional imaging method of staging, assessment of treatment, and monitoring of the lymphomas, sarcomas and neuroblastomas which can improve the results of treatment. The possibilities of using PET/CT in diagnostics of Wilms’ tumor, hepatoblastomas and germ cell tumors were reviewed. Key words: positron emission tomography, 18F-fluorodeoxyglucose, pediatric malignancies.

Delayed post-diuretic 18F-FDG PET/CT for preoperative evaluation of renal pelvic cancer

Background: Application of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in urological oncology was relatively slowly due to the urinary elimination of 18F-FDG. We investigated whether delayed post-diuretic 18F-FDG PET/CT could be used for diagnosing renal pelvic cancer.Methods: 51 patients were included who underwent delayed post-diuretic 18F-FDG PET/CT for detecting renal pelvic space-occupying lesions. The comparations of delayed PET/CT parameters and clinical characteristics between renal pelvic cancer and benign polyp were investigated.Results: Among the 51 patients, 47 were found to have renal pelvic urothelial carcinoma, and 4 had benign polyp. ROC analysis identified the lesion maximum standardized uptake value (SUVmax) of 6.2 as the optimal cut-off value to distinguish from renal pelvic urothelial carcinoma to benign polyp. With the SUVmax cut-off of 6.2, the sensitivity, and specificity for predicting of renal pelvic urothelial carcinoma were 91.5% (43/47), and 100% (4/4). We also found a significant difference in tumor size between the positive (SUVmax > 6.2) and negative (SUVmax ≤ 6.2) PET groups in renal pelvic cancers. In patients with tumor size < 1.1 cm, the probability of being in the negative PET group was 75%. In such patients, a substantial proportion of renal pelvic cancer demonstrated negative SUVmax similar to that in patients with benign polyp.Conclusion: Delayed 18F-FDG PET/CT could be used for differentiating renal pelvic cancer from benign polyp. In patients with small tumor size, renal pelvic cancer may present low 18F-FDG uptake, mimicking the metabolic phenotypes of patients with benign polyp.

Evaluation of D-isomer of 18F-FBPA for oncology PET focusing on the differentiation of glioma and inflammation.

L-4-borono-2-18F-fluoro-phenylalanine (L-[18F]FBPA), a substrate of L-type amino acid transporter 1 (LAT1), is a tumor-specific probe used in positron emission tomography (PET). On the other hand, it has not been examined whether another isomer D-[18F]FBPA accumulates specifically in the tumor. Here, we compared the accumulation of D-[18F]FBPA in C6 glioma and inflammation to evaluate the performance of D-[18F]FBPA as a tumor-specific probe. HEK293-LAT1 and HEK293-LAT2 cells were tested for [14C]-leucine or [14C]-alanine transport, and IC50 values of L- and D-FBPA were evaluated in both cell types. PET was conducted in rat xenograft model of C6 glioma with LAT1 expression and model of turpentine oil-induced subcutaneous inflammation (n=10 for both models). The concentrations of D-[18F]FBPA were compared between glioma and inflammatory lesion using standardized uptake value (SUV). In contrast to L-FBPA, which inhibited substrate uptake in both HEK293-LAT1 and -LAT2 cells, D-FBPA showed no inhibitory effect on both cells, suggesting low transporter selectivity of D-[18F]FBPA against LAT1 and LAT2. Static PET analysis showed low accumulation of D-[18F]FBPA in C6 glioma and inflammatory lesion (SUVmax=0.80±0.16, 0.56±0.09, respectively). Although there was a statistical difference in SUVmax between these tissues, it was difficult to distinguish glioma from inflammation on the PET image due to its low uptake level. Therefore, it was suggested that D-[18F]FBPA is not a suitable tumor-specific probe for oncology PET in contrast to L-[18F]FBPA. This study demonstrated that D-[18F]FBPA is not a LAT1-specific PET probe and shows low uptake in C6 glioma, indicating its unsuitability as a tumor diagnosis PET probe.

Biochemical basics of imaging in positron emission tomography in oncology. Part 1

This article provides a literature overview of biochemical basics and the clinical application of positron emission tomography, one of the most promising technologies of nuclear imaging in oncology. In the first part we discuss the biokinetics of metabolic radiopharmaceuticals, such as 18F-fluorodeoxyglucose, radiolabeled markers of lipid metabolism 11C- and 18F-choline, 11C-acetate, as well as amino acids analogues – 18F-dihydroxyphenylalanine, 11C-methionine, 18F-fluoroe thyltyrosine, 11C-tryptophan, 18F-flucyclovine. This article includes results of scientific researches, that studied radiopharmaceuticals’ effectiveness in oncological practice. The main indications for use, as well as promising scientific developments in this industry are presented.

18F-2-fluoro-2-deoxyglucose uptake in white adipose tissue on pediatric oncologic positron emission tomography (PET)/computed tomography (CT).

Altered biodistribution of [F-18]2-fluoro-2-deoxyglucose (FDG) is sometimes encountered in pediatric patients undergoing chemotherapy for lymphoma on post-induction positron emission tomography (PET) imaging. A characteristic pattern of increased FDG uptake in white adipose tissue can be seen, particularly in the buccal regions, body wall and gluteal regions, with a shift of radiotracer away from the blood pool and liver. This altered biodistribution has been attributed to effects of corticosteroids in pediatric and adult patients and is important to recognize because of its potential for limiting the diagnostic quality of the PET scan and interfering with therapeutic response assessment. In contrast to the well-known metabolically active brown fat seen on up to one-third of pediatric PET scans, white fat is usually non-metabolically active. We sought to determine the incidence of altered distribution of FDG in subcutaneous white adipose tissue in pediatric patients undergoing PET imaging and to assess the association with corticosteroid use. We reviewed the medical records and imaging for four children in whom altered biodistribution in white adipose tissue was present on post-induction FDG PET/CT, identified during routine clinical practice. All four were receiving corticosteroids as part of their chemotherapy. We then retrospectively reviewed oncology FDG PET/CT scans over a 2-year period (1,361 scans in 689 patients) to determine the incidence of uptake in white fat by qualitative visual assessment. In the children identified with altered biodistribution, we measured maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean) in areas of subcutaneous white fat, the buccal regions, body wall or gluteal soft-tissue regions, liver and blood pool. We reviewed all medical records, including medication lists. We summarize the relevant clinical and imaging findings of 13 pediatric patients, including the 4 index patients. We determined the incidence of FDG uptake in white fat to be rare, found in 9 of 1,361 (0.6%) PET scans performed for pediatric cancer evaluation. FDG uptake was increased in subcutaneous adipose tissue, particularly in the buccal regions, body wall and gluteal regions, with a shift of radiotracer away from the blood pool and liver. The degree of increased uptake in peripheral white fat varied from marked to mild, and the biodistribution was distinct from that of brown adipose tissue. Children with this altered biodistribution were uniformly receiving corticosteroids as part of induction treatment for their cancer, and these findings were only identified on post-induction PET/CT. Follow-up PET/CT documented resolution of this effect after treatment with corticosteroids ceased. Our findings support the current understanding that characteristic uptake of FDG in white adipose tissue is mediated by corticosteroid effect. Although this altered biodistribution is rare (<1% of PET scans) it could impair the diagnostic quality of the scan, affecting image interpretation, and should be recognized when present.

Simultaneous maximum a posteriori longitudinal PET image reconstruction

Positron emission tomography (PET) is frequently used to monitor functional changes that occur over extended time scales, for example in longitudinal oncology PET protocols that include routine clinical follow-up scans to assess the efficacy of a course of treatment. In these contexts PET datasets are currently reconstructed into images using single-dataset reconstruction methods. Inspired by recently proposed joint PET-MR reconstruction methods, we propose to reconstruct longitudinal datasets simultaneously by using a joint penalty term in order to exploit the high degree of similarity between longitudinal images. We achieved this by penalising voxel-wise differences between pairs of longitudinal PET images in a one-step-late maximum a posteriori (MAP) fashion, resulting in the MAP simultaneous longitudinal reconstruction (SLR) method. The proposed method reduced reconstruction errors and visually improved images relative to standard maximum likelihood expectation-maximisation (ML-EM) in simulated 2D longitudinal brain tumour scans. In reconstructions of split real 3D data with inserted simulated tumours, noise across images reconstructed with MAP-SLR was reduced to levels equivalent to doubling the number of detected counts when using ML-EM. Furthermore, quantification of tumour activities was largely preserved over a variety of longitudinal tumour changes, including changes in size and activity, with larger changes inducing larger biases relative to standard ML-EM reconstructions. Similar improvements were observed for a range of counts levels, demonstrating the robustness of the method when used with a single penalty strength. The results suggest that longitudinal regularisation is a simple but effective method of improving reconstructed PET images without using resolution degrading priors.

18F-Fluorination of Unactivated C-H Bonds in Branched Aliphatic Amino Acids: Direct Synthesis of Oncological Positron Emission Tomography Imaging Agents.

A mild and selective photocatalytic C-H 18F-fluorination reaction has been developed that provides direct access to 18F-fluorinated amino acids. The biodistribution and uptake of three 18F-labeled leucine analogues via LAT1 mediated transport in several cancer cell lines is reported. Positron emission tomography imaging of mice bearing PC3 (prostate) or U87 (glioma) xenografts using 5-[18F]-fluorohomoleucine showed high tumor uptake and excellent tumor visualization, highlighting the utility of this strategy for rapid tracer discovery for oncology.

Current Progresses in Developing PET Radiopharmaceuticals for Patients in the Czech Republic

In Masaryk Memorial Cancer Institute (MMCI), there is a long-running intensive joint effort of the RECAMO project and commercial entities, involving mainly clinical evaluations of state-of-the-art PET radiopharmaceuticals leading to their future availability for Czech physicians and their patients. Recently, the PET tracers [11C]methionine and [18F]fluorocholine, among others, were developed in this cooperation, both of them tracers with high importance for oncologic positron emission tomography diagnostics. [11C]methionine, labeled by carbon-11 with a half-life of 20 min, is a proteosynthesis marker used primarily for brain tumor visualization, whereas [18F]fluorocholine, labeled by fluorine-18 with a half-life of 109 min, is a marker of synthesis of cellular membranes and cell proliferation, its primary use being PET diagnostics of prostate carcinoma.The results of clinical evaluations of both PET radiopharmaceuticals, performed on the basis of parameters agreed and approved beforehand in cooperation of MMCI, RECAMO and the manufacturer of said radiopharmaceuticals, aimed to prove the efficiency and suitability of both compounds for oncologic PET diagnostics for said tumors. In both cases, the radiopharmaceuticals were evaluated in regard to their major use.The obtained results prove the benefits and efficiency of both compounds in PET diagnostics of respective tumors. The results, in the form of clinical evaluation reports, will be used as part of the documentation required for marketing authorization of these compounds for use in the Czech Republic.Key words: positron emission tomography - radiopharmaceuticals - L-methyl-11C-methionine - 18F-fluorocholineThis work was supported by the project MEYS - NPS I - LO1413.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 10. 6. 2016Accepted: 17. 6. 2016.