Sequential Positron Emission Tomography Research Articles

Small animal PET with spontaneous inhalation of 15O-labelled oxygen gases: Longitudinal assessment of cerebral oxygen metabolism in a rat model of neonatal hypoxic-ischaemic encephalopathy

Perinatal hypoxic-ischaemic encephalopathy (HIE) is the leading cause of irreversible brain damage resulting in serious neurological dysfunction among neonates. We evaluated the feasibility of positron emission tomography (PET) methodology with 15O-labelled gases without intravenous or tracheal cannulation for assessing temporal changes in cerebral blood flow ( CBF ) and cerebral metabolic rate for oxygen ( CMRO2 ) in a neonatal HIE rat model. Sequential PET scans with spontaneous inhalation of 15O-gases mixed with isoflurane were performed over 14 days after the hypoxic-ischaemic insult in HIE pups and age-matched controls. CBF and CMRO2 in the injured hemispheres of HIE pups remarkably decreased 2 days after the insult, gradually recovering over 14 days in line with their increase found in healthy controls according to their natural maturation process. The magnitude of hemispheric tissue loss histologically measured after the last PET scan was significantly correlated with the decreases in CBF and CMRO2. This fully non-invasive imaging strategy may be useful for monitoring damage progression in neonatal HIE and for evaluating potential therapeutic outcomes.

Sequential and Hybrid PET/MRI Acquisition in Follow-Up Examination of Glioblastoma Show Similar Diagnostic Performance.

Both positron emission tomography (PET) and magnetic resonance imaging (MRI), including dynamic susceptibility contrast perfusion (DSC-PWI), are crucial for treatment monitoring of patients with high-grade gliomas. In clinical practice, they are usually conducted at separate time points. Whether this affects their diagnostic performance is presently unclear. To this end, we retrospectively reviewed 38 patients with pathologically confirmed glioblastoma (IDH wild-type) and suspected tumor recurrence after radiotherapy. Only patients who received both a PET−MRI (where DSC perfusion was acquired simultaneously with a FET-PET) and a separate MRI exam (including DSC perfusion) were included. Tumors were automatically segmented into contrast-enhancing tumor (CET), necrosis, and edema. To compare the simultaneous as well as the sequential DSC perfusion to the FET-PET, we calculated Dice overlap, global mutual information as well as voxel-wise Spearman correlation of hotspot areas. For the joint assessment of PET and MRI, we computed logistic regression models for the differentiation between true progression (PD) and treatment-related changes (TRC) using simultaneously or sequentially acquired images as input data. We observed no significant differences between Dice overlap (p = 0.17; paired t-test), mutual information (p = 0.18; paired t-test) and Spearman correlation (p = 0.90; paired t-test) when comparing simultaneous PET−MRI and sequential PET/MRI acquisition. This also held true for the subgroup of patients with >14 days between exams. Importantly, for the diagnostic performance, ROC analysis showed similar AUCs for differentiation of PD and TRC (AUC simultaneous PET: 0.77; AUC sequential PET: 0.78; p = 0.83, DeLong’s test). We found no relevant differences between simultaneous and sequential acquisition of FET-PET and DSC perfusion, also regarding their diagnostic performance. Given the increasing attention to multi-parametric assessment of glioma treatment response, our results reassuringly suggest that sequential acquisition is clinically and scientifically acceptable.

Incorporating coronary artery calcium scoring in the prediction of obstructive coronary artery disease with myocardial ischemia: a study with sequential use of coronary computed tomography angiography and positron emission tomography imaging

BackgroundAdditional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD. Methods and resultsSymptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [15O]H2O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion ≤ 2.4 mL/g/min in ≥ 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 ± 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P < .001). AUC for the discrimination of ischemia for the CACS model was superior over the basic model and risk factor model (P < .001). ConclusionsAdding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD.

Evidence of a Gastro-Duodenal Effect on Adipose Tissue and Brain Metabolism, Potentially Mediated by Gut-Liver Inflammation: A Study with Positron Emission Tomography and Oral 18FDG in Mice.

Interventions affecting gastrointestinal (GI) physiology suggest that the GI tract plays an important role in modulating the uptake of ingested glucose by body tissues. We aimed at validating the use of positron emission tomography (PET) with oral 18FDG administration in mice, and to examine GI effects on glucose metabolism in adipose tissues, brain, heart, muscle, and liver, and interfering actions of oral lipid co-administration. We performed sequential whole-body PET studies in 3 groups of 10 mice, receiving i.p. glucose and 18FDG or oral glucose and 18FDG ± lipids, to measure tissue glucose uptake (GU) and GI transit, and compute the absorption lumped constant (LCa) as ratio of oral 18FDG-to-glucose incremental blood levels. GI and liver histology and circulating hormones were tested to generate explanatory hypothesis. Median LCa was 1.18, constant over time and not significantly affected by lipid co-ingestion. Compared to the i.p. route, the oral route (GI effect) resulted in lower GU rates in adipose tissues and brain, and a greater steatohepatitis score (+17%, p = 0.03). Lipid co-administration accelerated GI transit, in relation to the suppression in GIP, GLP1, glucagon, PP, and PYY (GI motility regulators), abolishing GI effects on subcutaneous fat GU. Duodenal crypt size, gastric wall 18FDG uptake, and macro-vesicular steatosis were inversely related to adipose tissue GU, and positively associated with liver GU. We conclude that 18FDG-PET is a suitable tool to examine the role of the GI tract on glucose transit, absorption, and bio-distribution. The GI effect consists in the suppression of glucose metabolism selectively in organs responsible for energy intake and storage, and is blunted by lipid ingestion. Modulation of gut and liver inflammation, as reflected by high GU, may be involved in the acute signalling of the energy status.

Pancreatic GLP-1r binding potential is reduced in insulin-resistant pigs

IntroductionThe insulinotropic capacity of exogenous glucagon like peptide-1 (GLP-1) is reduced in type 2 diabetes and the insulin-resistant obese. We have tested the hypothesis that this response is the consequence...

A preclinical PET dual-tracer imaging protocol for ER and HER2 phenotyping in breast cancer xenografts

BackgroundNuclear medicine is on the constant search of precision radiopharmaceutical approaches to improve patient management. Although discordant expression of the estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2) in breast cancer is a known dilemma for appropriate patient management, traditional tumor sampling is often difficult or impractical. While 2-deoxy-2[18F]fluoro-D-glucose (18F-FDG)-positron emission tomography (PET) is an option to detect subclinical metastases, it does not provide phenotype information. Radiolabeled antibodies are able to specifically target expressed cell surface receptors. However, their long circulating half-lives (days) require labeling with long-lived isotopes, such as 89Zr, in order to allow sufficient time for tracer clearance from the blood compartment and to accumulate adequately in target tumors and, thus, generate high-quality PET images. The aim of this study was to develop a dual-tracer PET imaging approach consisting of a fast-clearing small molecule and a slow-clearing antibody. This approach was evaluated in a model consisting of mice harboring separate breast cancer xenografts with either an ER+/HER2− or ER−/HER2+ phenotype, comparable to human metastatic disease with intertumor heterogeneity. Lastly, the aim of our study was to determine the feasibility of specifically identifying these two important phenotypes in an acceptable time window.MethodsFemale nude mice were subcutaneously implanted on opposite shoulders with the ER+/HER2− and ER−/HER2+ MCF-7 and JIMT-1 tumor cell lines, respectively. A second model was developed consisting of mice implanted orthotopically with either MCF-7 or JIMT-1 cells. Pharmacokinetic analysis, serial PET imaging, and biodistribution were first performed for [89Zr]Zr-DFO-trastuzumab (89Zr-T) up to 8 days post-injection (p.i.) in JIMT-1 bearing mice. Region-of-interest (ROI) and biodistribution-derived uptake (% injected-activity/gram of tissue [%IA/g]) values and tumor-to-background ratios were obtained. Results were compared in order to validate ROI and identify early time points that provided high contrast tumor images. For the dual-tracer approach, cohorts of tumor-bearing mice were then subjected to sequential tracer PET imaging. On day 1, mice were administered 4-fluoro-11β-methoxy-16α-[18F]-fluoroestradiol (4FMFES) which targets ER and imaged 45 min p.i. This was immediately followed by the injection of 89Zr-T. Mice were then imaged on day 3 or day 7. ROI analysis was performed, and uptake was calculated in tumors and selected healthy organs for all radiotracers. Quality of tumor targeting for all tracers was evaluated by tumor contrast visualization, tumor and normal tissue uptake, and tumor-to-background ratios.Results89Zr-T provided sufficiently high tumor and low background uptake values that furnished high contrast tumor images by 48 h p.i. For the dual-tracer approach, 4FMFES provided tumor uptake values that were significantly increased in MCF-7 tumors. When 89Zr-T-PET was combined with 18F-4FMFES-PET, the entire dual-tracer sequential-imaging procedure provided specific high-quality contrast images of ER+/HER2− MCF-7 and ER−/HER2+ JIMT-1 tumors for 4FMFES and 89Zr-T, respectively, as short as 72 h from start to finish.ConclusionsThis protocol can provide high contrast images of tumors expressing ER or HER2 within 3 days from injection of 4FMFES to final scan of 89Zr-T and, hence, provides a basis for future dual-tracer combinations that include antibodies.

Deep learning-based attenuation correction in the absence of structural information for whole-body positron emission tomography imaging

Deriving accurate structural maps for attenuation correction (AC) of whole-body positron emission tomography (PET) remains challenging. Common problems include truncation, inter-scan motion, and erroneous transformation of structural voxel-intensities to PET µ-map values (e.g. modality artifacts, implanted devices, or contrast agents). This work presents a deep learning-based attenuation correction (DL-AC) method to generate attenuation corrected PET (AC PET) from non-attenuation corrected PET (NAC PET) images for whole-body PET imaging, without the use of structural information. 3D patch-based cycle-consistent generative adversarial networks (CycleGAN) is introduced to include NAC-PET-to-AC-PET mapping and inverse mapping from AC PET to NAC PET, which constrains NAC-PET-to-AC-PET mapping to be closer to one-to-one mapping. Since NAC PET images share similar anatomical structures to the AC PET image but lack contrast information, residual blocks, which aim to learn the differences between NAC PET and AC PET, are used to construct generators of CycleGAN. After training, patches from NAC PET images were fed into NAC-PET-to-AC-PET mapping to generate DL-AC PET patches. DL-AC PET image was then reconstructed through patch fusion. We conducted a retrospective study on 55 datasets of whole-body PET/CT scans to evaluate the proposed method. In comparing DL-AC PET with original AC PET, average mean error (ME) and normalized mean square error (NMSE) of the whole-body were 0.62% ± 1.26% and 0.72% ± 0.34%. The average intensity changes measured on sequential PET images with AC and DL-AC on both normal tissues and lesions differ less than 3%. There was no significant difference of the intensity changes between AC and DL-AC PET, which demonstrate DL-AC PET images generated by the proposed DL-AC method can reach a same level to that of original AC PET images. The method demonstrates excellent quantification accuracy and reliability and is applicable to PET data collected on a single PET scanner or hybrid platform with computed tomography (PET/CT) or magnetic resonance imaging (PET/MRI).

Biodistribution and radiation dosimetry of [18F]-JK-PSMA-7 as a novel prostate-specific membrane antigen-specific ligand for PET/CT imaging of prostate cancer

AimWe investigated the whole-body distribution and the radiation dosimetry of [18F]-JK-PSMA-7, a novel 18F-labeled PSMA-ligand for PET/CT imaging of prostate cancer.MethodsTen patients with prostate cancer and biochemical recurrence or radiologic evidence of metastatic diseases were examined with 329–384 MBq (mean 359 ± 17 MBq) [18F]-JK-PSMA-7. Eight sequential positron emission tomography (PET) scans were acquired from 20 min to 3 h after injection with IRB approval. The kidneys, liver, lungs, spleen, and salivary glands were segmented into volumes of interest using the QDOSE dosimetry software suite (ABX-CRO, Germany). Absorbed and effective dose were calculated using the ICRP-endorsed IDAC 1.0 package. The absorbed dose of the salivary glands was determined using the spherical model of OLINDA 1.1. PSMA-positive lesions were evaluated separately. Quantitative assessment of the uptake in suspicious lesions was performed by analysis of maximum (max) and peak SUV values. The gluteus maximus muscle (SUVmean) served as a reference region for the calculation of tumor-to-background ratios (TBR’s).ResultsPhysiologic radiotracer accumulation was observed in the salivary and lacrimal glands, liver, spleen, and intestines, in a pattern resembling the distribution known from other PSMA-tracers with excretion via urinary and biliary pathways. The effective dose from [18F]-JK-PSMA-7 for the whole body was calculated to be 1.09E−02 mGy/MBq. The highest radiation dose was observed in the kidneys (1.76E−01 mGy/MBq), followed by liver (7.61E−02 mGy/MBq), salivary glands (4.68E−02 mGy/MBq), spleen (1.89E−02 mGy/MBq), and lungs (1.10E-2 mGy/MBq). No adverse effects of tracer injection were observed. Six out of ten patients were scored as PSMA-positive. A total of 18 suspicious lesions were analyzed, which included six bone lesions, nine lymph nodes, and three local lesions within the prostate fossa. The values for the SUVmax and SUVpeak in the PSMA-positive lesions increased until 60 min p.i. and remained at this intensity in the PET/CT scans until 140 min. In the period between 170 and 200 min after injection, a further significant increase in SUVmax and SUVpeak within the PSMA-positive lesions was observed.ConclusionsThe highest TBR of [18F]-JK-PSMA-7 was found 3 h after injection. From the kinetically collected data, it can be concluded that this trend may also continue in the further course. The start of the PET/CT acquisition should be chosen as late as possible. The high uptake in suspicious lesions in terms of absolute SUVmax and relative TBR values indicates potentially high sensitivity of the tracer for detection of prostate cancer manifestations.

Imaging acquisition technique influences interpretation of positron emission tomography vascular activity in large-vessel vasculitis

ObjectivesTo determine the impact of imaging acquisition time on interpretation of disease activity on 18F-fluorodeoxyglucose positron emission tomography (PET) in large-vessel vasculitis (LVV) and assess the relationship between clinical features and image acquisition time. MethodsPatients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK) were recruited into a prospective, observational cohort. After a single injection of FDG, all patients underwent two sequential PET scans at one and two-hour time points. Images were interpreted for active vasculitis by subjective assessment, qualitative assessment, and semi-quantitative assessment. Agreement was assessed by percent agreement, Cohen's kappa, and McNemar's test. Multivariable logistic regression identified associations between PET activity and clinical variables. Results79 patients (GCA = 44, TAK = 35) contributed 168 paired one and two-hour PET studies. A total of 94 out of 168 scans (56%) were interpreted as active at the one-hour time point, and 129 scans (77%) were interpreted as active at the two-hour time point (p < 0.01). Associations between clinical variables and PET activity categories (dual inactive, delayed active, dual active) were evaluated. Using multivariable nominal regression, clinically active disease was significantly more common in patients in the delayed active group (Odds Ratio 1.94, 95%CI 1.13–3.53; p = 0.02) and the dual active group (Odds Ratio 1.71, 95%CI 1.06–2.93; p = 0.04) compared to the dual inactive group. ConclusionsImaging protocol significantly influences interpretation of PET activity in LVV. A substantial proportion of patients with LVV have PET activity only detected by delayed imaging. These patients were significantly more likely to have concomitant clinically-determined active disease.

Primary Cardiac Angiosarcoma with Extensive Visceral Metastases: Utility of 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Response Assessment to Sorafenib.

Primary cardiac angiosarcomas although rare neoplasms remain the most common primary malignant neoplasms affecting the heart. We discuss the sequential positron-emission tomography–computed tomography findings of a 50-year-old man who was diagnosed with the metastatic cardiac angiosarcoma at the outset and developed progressive disease despite sorafenib therapy.

Transient aortitis documented by positron emission tomography in a case series of men and transgender women infected with syphilis

ObjectivesSyphilis infection persists globally contributing to preventable and treatable morbidity and mortality. How extensive early syphilis disseminates is unknown. To better understand the relationship between early syphilis infection and inflammation...

Brain PET and functional MRI: why simultaneously using hybrid PET/MR systems?

In the last 20 years growing attention has been devoted to multimodal imaging. The recent literature is rich of clinical and research studies that have been performed using different imaging modalities on both separate and integrated positron emission tomography (PET) and magnetic resonance (MR) scanners. However, today, hybrid PET/MR systems measure signals related to brain structure, metabolism, neurochemistry, perfusion, and neuronal activity simultaneously, i.e. in the same physiological conditions. A frequently raised question at meeting and symposia is: "Do we really need a hybrid PET/MR system? Are there any advantages over acquiring sequential and separate PET and MR scans?" The present paper is an attempt to answer these questions specifically in relation to PET combined with functional magnetic resonance imaging (fMRI) and arterial spin labeling. We searched (last update: June 2017) the databases PubMed, PMC, Google Scholar and Medline. We also included additional studies if they were cited in the selected articles. No language restriction was applied to the search, but the reviewed articles were all in English. Among all the retrieved articles, we selected only those performed using a hybrid PET/MR system. We found a total of 17 papers that were selected and discussed in three main groups according to the main radiopharmaceutical used: 18F-fluorodeoxyglucose (18F-FDG) (N.=8), 15O-water (15O-H2O) (N.=3) and neuroreceptors (N.=6). Concerning studies using 18F-FDG, simultaneous PET/fMRI revealed that global aspects of functional organization (e.g. graph properties of functional connections) are partially associated with energy consumption. There are remarkable spatial and functional similarities across modalities, but also discrepant findings. More work is needed on this point. There are only a handful of papers comparing blood flow measurements with PET 15O-H2O and MR arterial spin label (ASL) measures, and they show significant regional CBF differences between these two modalities. However, at least in one study the correlation at the level of gray, white matter, and whole brain is rather good (r=0.94, 0.8, 0.81 respectively). Finally, receptor studies show that simultaneous PET/fMRI could be a useful tool to characterize functional connectivity along with dynamic neuroreceptor adaptation in several physiological (e.g. working memory) or pathological (e.g. pain) conditions, with or without drug administrations. The simultaneous acquisition of PET (using a number of radiotracers) and functional MRI (using a number of sequences) offers exciting opportunities that we are just beginning to explore. The results thus far are promising in the evaluation of cerebral metabolism/flow, neuroreceptor adaptation, and network's energetic demand.

Discovery of 1,2,3-Triazole Derivatives for Multimodality PET/CT/Cryoimaging of Myelination in the Central Nervous System.

Myelin pathology is present in many neurological conditions such as multiple sclerosis (MS) and traumatic spinal cord injury (SCI). To facilitate development of novel therapies aimed at myelin repair, we set out to develop imaging agents that permit direct quantification of myelination in vivo. In this work, we designed and synthesized a series of fluorescent fluorinated myelin imaging agents that can be used for in vivo positron emission tomography (PET) imaging combined with subsequent post-mortem fluorescent cryoimaging. Structure-activity relationship (SAR) studies of the newly developed myelin imaging agents led us to identify a lead compound (TAFDAS, 21) that readily enters the brain and spinal cord and selectively binds to myelin. By conducting sequential PET and 3D cryoimaging in an SCI rat model, we demonstrated for the first time that PET and cryoimaging can be combined as a novel technique to image the spinal cord with high sensitivity and spatial resolution.

CD146-targeted immunoPET and NIRF Imaging of Hepatocellular Carcinoma with a Dual-Labeled Monoclonal Antibody

Overexpression of CD146 has been correlated with aggressiveness, recurrence rate, and poor overall survival in hepatocellular carcinoma (HCC) patients. In this study, we set out to develop a CD146-targeting probe for high-contrast noninvasive in vivo positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of HCCs. YY146, an anti-CD146 monoclonal antibody, was employed as a targeting molecule to which we conjugated the zwitterionic near-infrared fluorescence (NIRF) dye ZW800-1 and the chelator deferoxamine (Df). This enabled labeling of Df-YY146-ZW800 with 89Zr and its subsequent detection using PET and NIRF imaging, all without compromising antibody binding properties. Two HCC cell lines expressing high (HepG2) and low (Huh7) levels of CD146 were employed to generate subcutaneous (s.c.) and orthotopic xenografts in athymic nude mice. Sequential PET and NIRF imaging performed after intravenous injection of 89Zr-Df-YY146-ZW800 into tumor-bearing mice unveiled prominent and persistent uptake of the tracer in HepG2 tumors that peaked at 31.65 ± 7.15 percentage of injected dose per gram (%ID/g; n=4) 72 h post-injection. Owing to such marked accumulation, tumor delineation was successful by both PET and NIRF, which facilitated the fluorescence image-guided resection of orthotopic HepG2 tumors, despite the relatively high liver background. CD146-negative Huh7 and CD146-blocked HepG2 tumors exhibited significantly lower 89Zr-Df-YY146-ZW800 accretion (6.1 ± 0.5 and 8.1 ± 1.0 %ID/g at 72 h p.i., respectively; n=4), demonstrating the CD146-specificity of the tracer in vivo. Ex vivo biodistribution and immunofluorescent staining corroborated the accuracy of the imaging data and correlated tracer uptake with in situ CD146 expression. Overall, 89Zr-Df-YY146-ZW800 showed excellent properties as a PET/NIRF imaging agent, including high in vivo affinity and specificity for CD146-expressing HCC. CD146-targeted molecular imaging using dual-labeled YY146 has great potential for early detection, prognostication, and image-guided surgical resection of liver malignancies.

Joint tumor growth prediction and tumor segmentation on therapeutic follow-up PET images.

Tumor response to treatment varies among patients. Patient-specific prediction of tumor evolution based on medical images during the treatment can help to build and adapt patient's treatment planning in a non-invasive way. Personalized tumor growth modeling allows patient-specific prediction by estimating model parameters based on individual's images. The model parameters are often estimated by optimizing a cost function constructed based on the tumor delineations. In this paper, we propose a joint framework for tumor growth prediction and tumor segmentation in the context of patient's therapeutic follow ups. Throughout the treatment, a series of sequential positron emission tomography (PET) images are acquired for tumor response monitoring. We propose to take into account the predicted information, which is used in combination with the random walks (RW) algorithm, to develop an automatic tumor segmentation method on PET images. Moreover, we propose an iterative scheme of RW, making the segmentation more performant. Furthermore, the obtained segmentation is applied to the process of model parameter estimation so as to get the model based prediction of tumor evolution. We evaluate our methods on 7 lung tumor patients, totaling 29 PET exams, under radiotherapy by comparing the obtained tumor prediction and tumor segmentation with manual tumor delineation by expert. Our system produces promising results when compared to the state-of-the-art methods.

Initial Evaluation of [(18)F]DCFPyL for Prostate-Specific Membrane Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a recognized target for imaging prostate cancer. Here we present initial safety, biodistribution, and radiation dosimetry results with [(18)F]DCFPyL, a second-generation fluorine-18-labeled small-molecule PSMA inhibitor, in patients with prostate cancer. Biodistribution was evaluated using sequential positron-emission tomography (PET) scans in nine patients with prostate cancer. Time-activity curves from the most avid tumor foci were determined. The radiation dose to selected organs was estimated using OLINDA/EXM. No major radiotracer-specific adverse events were observed. Physiologic accumulation was observed in known sites of PSMA expression. Accumulation in putative sites of prostate cancer was observed (SUVmax up to >100, and tumor-to-blood ratios up to >50). The effective radiation dose from [(18)F]DCFPyL was 0.0139mGy/MBq or 5mGy (0.5rem) from an injected dose of 370MBq (10mCi). [(18)F]DCFPyL is safe with biodistribution as expected, and its accumulation is high in presumed primary and metastatic foci. The radiation dose from [(18)F]DCFPyL is similar to that from other PET radiotracers.

Sensitivity study of voxel-based PET image comparison to image registration algorithms.

Accurate deformable registration is essential for voxel-based comparison of sequential positron emission tomography (PET) images for proper adaptation of treatment plan and treatment response assessment. The comparison may be sensitive to the method of deformable registration as the optimal algorithm is unknown. This study investigated the impact of registration algorithm choice on therapy response evaluation. Sixteen patients with 20 lung tumors underwent a pre- and post-treatment computed tomography (CT) and 4D FDG-PET scans before and after chemoradiotherapy. All CT images were coregistered using a rigid and ten deformable registration algorithms. The resulting transformations were then applied to the respective PET images. Moreover, the tumor region defined by a physician on the registered PET images was classified into progressor, stable-disease, and responder subvolumes. Particularly, voxels with standardized uptake value (SUV) decreases >30% were classified as responder, while voxels with SUV increases >30% were progressor. All other voxels were considered stable-disease. The agreement of the subvolumes resulting from difference registration algorithms was assessed by Dice similarity index (DSI). Coefficient of variation (CV) was computed to assess variability of DSI between individual tumors. Root mean square difference (RMSrigid) of the rigidly registered CT images was used to measure the degree of tumor deformation. RMSrigid and DSI were correlated by Spearman correlation coefficient (R) to investigate the effect of tumor deformation on DSI. Median DSIrigid was found to be 72%, 66%, and 80%, for progressor, stable-disease, and responder, respectively. Median DSIdeformable was 63%-84%, 65%-81%, and 82%-89%. Variability of DSI was substantial and similar for both rigid and deformable algorithms with CV > 10% for all subvolumes. Tumor deformation had moderate to significant impact on DSI for progressor subvolume with Rrigid = - 0.60 (p = 0.01) and Rdeformable = - 0.46 (p = 0.01-0.20) averaging over all deformable algorithms. For stable-disease subvolumes, the correlations were significant (p < 0.001) for all registration algorithms with Rrigid = - 0.71 and Rdeformable = - 0.72. Progressor and stable-disease subvolumes resulting from rigid registration were in excellent agreement (DSI > 70%) for RMSrigid < 150 HU. However, tumor deformation was observed to have negligible effect on DSI for responder subvolumes with insignificant |R| < 0.26, p > 0.27. This study demonstrated that deformable algorithms cannot be arbitrarily chosen; different deformable algorithms can result in large differences of voxel-based PET image comparison. For low tumor deformation (RMSrigid < 150 HU), rigid and deformable algorithms yield similar results, suggesting deformable registration is not required for these cases.

Nomogram Predicting Long-Term Survival After TME Surgery for Locally Advanced Rectal Cancer Based on 1798 Patients Treated in a Single Institution Between 2000 and 2010

Materials/Methods: cT3-4 rectal cancer patients were randomly assigned to receive either preoperative IG-IMRT (46 Gy in 23 fractions of 2 Gy) with a SIB to the rectal tumor up to a total dose of 55.2 Gy (boost-arm) or preoperative IG-IMRT (46 Gy in 23 fractions of 2 Gy) plus capecitabine (825 mg/m2 twice daily) (chemo-arm). Surgery was performed 6-8 weeks after completion of preoperative treatment. Metabolic tumor activity reduction, assessed by comparing the maximal standardized uptake value (SUVmax) on sequential 18-fluorodeoxyglucose positron emission tomography (FDG-PET), was the primary endpoint. Acute side effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: To date, 114 patients were randomly assigned to the boost-arm (n Z 55) or chemo-arm (n Z 59). Acute grade 3 toxicity occurred in 4% of the patients in the boost-arm compared to 7% in the chemo-arm (p Z 0.38). No acute grade 4 toxicities were observed. There was a trend for a lower rate of acute grade 2 enteritis in the boost-arm (25% vs 36% in the chemo-arm; p Z 0.16). The R0 resection rate was 98% for patients in the boostand chemo-arm. Pathologic complete response rate (ypCR, Dworak grade 4) was 16% in the boost-arm compared to 21% in the chemo-arm (p Z 0.33). Dworak regression grade 3-4 was 48% and 40% in the boost-arm and chemo-arm, respectively (p Z 0.27). The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT as compared to baseline was 53.5% 19.4% and 50.7% 25.7% for patients in the boost-arm and chemo-arm, respectively (p Z 0.28). Conclusions: The implementation of preoperative IG-IMRT resulted in limited acute grade 3 toxicity in both arms. In terms of downstaging, impressive rates of major histomorphologic regression (Dworak grade 3-4) were recorded in both treatment arms, with no significant difference in the ypCR rate. We observed no differences in metabolic response. Mature data from this ongoing trial are awaited later this year. Author Disclosure: B. Engels: None. A. De Paoli: None. G. Cattari: None. F. Munoz: None. S. Vagge: None. D. Norkus: None. P. Gabriele: None. G. Tabaro: None. H. Versmessen: None. M. De Ridder: None.

Adequacy of a compartment model for CMRO₂ quantitation using ¹⁵O-labeled oxygen and PET: a clearance measurement of ¹⁵O-radioactivity following intracarotid bolus injection of ¹⁵O-labeled oxyhemoglobin on Macaca fascicularis.

We aimed at evaluating the adequacy of the commonly employed compartmental model for quantitation of cerebral metabolic rate of oxygen (CMRO2) using 15O-labeled oxygen (15O2) and positron emission tomography (PET). Sequential PET imaging was carried out on monkeys following slow bolus injection of blood samples containing 15O2–oxyhemoglobin (15O2–Hb), 15O-labeled water (H215O), and C15O-labeled hemoglobin (C15O–Hb) into the internal carotid artery (ICA). Clearance slopes were assessed in the middle cerebral artery territory of the injected hemisphere. The time–activity curves were bi-exponential for both 15O2–Hb and H215O. Single exponential fitting to the early (5 to 40 seconds) and late (80 to 240 seconds) periods after the peak was performed and the 15O2–Hb and H215O results were compared. It was found that a significant difference between the clearance rates of the 15O2–Hb and H215O injections is unlikely, which supports the mathematical model that is widely used to describe the kinetics of 15O2–Hb and H215O in cerebral tissues and is the basis of recent approaches to simultaneously assess CMRO2 and cerebral blood flow in a single PET session. However, it should be noted that more data are necessary to unequivocally confirm the result.

Correlation between standardized uptake value in pre- and post-neoadjuvant chemoradiotherapy and tumor regression grade in patients with locally advanced esophageal cancer.

150 Background: A multimodality approach with neoadjuvant chemotherapy and radiation is the standard of care in the United States in the treatment of patients with locally advanced esophageal cancer. It is well established that neoadjuvant chemoradiotherapy (CRT) in these patients can facilitate downstaging, correlating with pathologic response, and improving overall survival. Our clinical practice involves the use of positron emission tomography (PET) to assist with staging in patients prior to undergoing neoadjuvant CRT and surgery. While there has been evidence showing correlation between tumor regression grade (TRG) and increased overall survival in these patients, the relationship between standardized uptake values on PET scans and TRG has not been discerned. The purpose of this study was to determine whether pre and post-chemoradiotherapy SUV on PET scans correlate with TRG in esophageal cancer patients receiving neoadjuvant chemoradiotherapy. Methods: A retrospective review of 56 patients with stage II-III esophageal cancer treated with neo-adjuvant CRT followed by surgery was performed. Pre- and post- treatment PET scans were reviewed. Maximum SUV at the site of the primary tumor was recorded. Upon completion of surgery, tumor regression grade was determined by a specialized pathologist. Spearman correlation was used to compare pre, post, and change in max SUV, to the 4 level TRG variables. Results: The median follow-up was 24 months. No significant correlation was found between pre-treatment or post treatment SUV and TRG with p value of 0.73 and 0.94 respectively. There was no significant correlation between decreased FDG uptake following CRT and TRG with p value of 0.82. Consistent with previous data, TRG predicted the therapeutic efficacy and prognosis for patients with locally advanced esophageal carcinoma treated by neoadjuvant chemotherapy. Conclusions: Our results are preliminary and retrospective in nature. A larger sample is needed to confirm these findings. Decreased FDG uptake in sequential PET scans strongly correlates with tumor response, but is not accurate enough to predict pathological response.