Modeling Patient-Specific Dose-Function Response for Enhanced Characterization of Personalized Functional Damage

PURPOSE: Functional-guided radiation therapy (RT) plans have the potential to limit damage to normal tissue and reduce toxicity. Although functional imaging modalities have continued to improve, a limited understanding of the functional response to radiation and its application to personalized therapy has hindered clinical implementation. The purpose of this study was to retrospectively model the longitudinal, patient-specific dose-function response in non-small cell lung cancer patients treated with RT to better characterize the expected functional damage in future, unknown patients. METHODS AND MATERIALS: Perfusion single-photon emission computed tomography/computed tomography scans were obtained at baseline (n = 81), midtreatment (n = 74), 3 months post-treatment (n = 51), and 1 year post-treatment (n = 26) and retrospectively analyzed. Patients were treated with conventionally fractionated RT or stereotactic body RT. Normalized perfusion single-photon emission computed tomography voxel intensity was used as a surrogate for local lung function. A patient-specific logistic model was applied to each individual patient's dose-function response to characterize functional reduction at each imaging time point. Patient-specific model parameters were averaged to create a population-level logistic dose-response model. RESULTS: A significant longitudinal decrease in lung function was observed after RT by analyzing the voxelwise change in normalized perfusion intensity. Generated dose-function response models represent the expected voxelwise reduction in function, and the associated uncertainty, for an unknown patient receiving conventionally fractionated RT or stereotactic body RT. Differential treatment responses based on the functional status of the voxel at baseline suggest that initially higher functioning voxels are damaged at a higher rate than lower functioning voxels. CONCLUSIONS: This study modeled the patient-specific dose-function response in patients with non-small cell lung cancer during and after radiation treatment. The generated population-level dose-function response models were derived from individual patient assessment and have the potential to inform functional-guided treatment plans regarding the expected functional lung damage. This type of patient-specific modeling approach can be applied broadly to other functional response analyses to better capture intrapatient dependencies and characterize personalized functional damage

Effect of blood glucose level on standardized uptake value (SUV) in F-18- FDG PET-scan : a systematic review and meta-analysis of 20,807 individual SUV measurements

Objectives To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in F-18-FDG-PET scan. Methods A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, F-18-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (200 mg/dl). Results Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p <0.001, p <0.001,) and muscle (p <0.001, p <0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p=0.008, p200 mg/dl had significantly lower SUVmax. Conclusion If BGL is lower than 200mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.Peer reviewe

A Case of Right Atrial Obliteration Caused by Intracardiac Extension of Hepatocellular Carcinoma

As the fifth most common malignancy worldwide, hepatocellular carcinoma (HCC) is a frequently encountered clinical entity. Symptomatology associated with the diagnosis includes hepatic dysfunction and pain from capsular spread. Additionally, due to its propensity for vascular spread, extrahepatic intravascular involvement can also be seen. We present a unique case of intracardiac involvement of HCC. Originally diagnosed as acute on chronic heart failure, echocardiography revealed the symptom source – tumor obliteration of the right atrium. Clinical case presentation and management, along with radiographic images are presented. A review of the current literature highlights this uncommon presentation and the need for clinical suspicion of cardiac involvement in patients with a history of HCC presenting with heart failure

Effect of hyperglycemia on brain and liver 18F-FDG standardized uptake value (FDG SUV) measured by quantitative positron emission tomography (PET) imaging

PurposeBlood glucose is routinely measured prior to 18F-fluorodeoxyglucose (FDG) administration in positron emission tomography (PET) imaging to identify hyperglycemia that may affect image quality. In this study we explore the effects of blood glucose levels upon semi-quantitative standardized uptake value (SUV) measurements of target organs and tissues of interest and in particular address the relationship of blood glucose to FDG accumulation in the brain and liver.Methods436 FDG PET/CT consecutive studies performed for oncology staging in 229 patients (226 male) at the Ann Arbor Veterans Administration Healthcare System were reviewed. All patients had blood glucose measured (112.4±34.1mg/dL) prior to injection of 466.2±51.8MBq (12.6±1.4mCi) of FDG. SUV measurements of brain, aortic arch blood-pool, liver, and spleen were obtained at 64.5±10.2min' post-injection.ResultsWe found a negative inverse relationship of brain SUV with increasing plasma glucose, levels for both absolute and normalized (either to blood-pool or liver) values. Higher blood glucose levels had a mild effect upon liver and blood-pool SUV. By contrast, spleen SUV was independent of blood glucose, but demonstrated the greatest variability (deviation on linear regression). In contrast to other tissues, liver and spleen SUV normalized to blood-pool SUV were not dependent upon blood glucose levels.ConclusionThe effects of hyperglycemia upon FDG uptake in brain and liver, over a range of blood glucose values generally considered acceptable for clinical PET imaging, may have measurable effects on semi-quantitative image analysis

3AcFNP-59 for Positron Emission Tomography Imaging of Cholesterol Trafficking and Utilization

Cholesteryl ester analogues of [18F]FNP-59 have the ability to provide information on cholesterol trafficking and utilization at earlier time points than those of [18F]FNP-59 or [131I]NP-59. It is well-known that free cholesterol and cholesteryl esters have differing distribution profiles and that they can be interconverted enzymatically. Substitution of the ester influences the rate of cholesterol ester hydrolysis and the subsequent mixing of cholesterol esters with the lipid pool in the body. This can be utilized by preparing esters that are more readily taken up by lipoprotein, are quickly hydrolyzed and mixed with the endogenous lipid pool and delivered to tissues of interest more quickly than free cholesterol analogues that require esterification for lipoprotein association. The acetyl ester of FNP-59 demonstrated the preferred uptake properties and response to adrenal cortical manipulation, indicating its ability to image hormone production. Finally, dosimetry studies were conducted in preparation for the clinical translation of [18F]3AcFNP-59

Synthesis and evaluation of 11C- and 18F-labeled SOAT1 inhibitors as macrophage foam cell imaging agents

PD-132301, an inhibitor of sterol -acyltransferase 1 (SOAT1; also known as acyl-coenzyme A:cholesterol acyltransferase-1, ACAT1), is under clinical investigation for numerous adrenal disorders. Radiolabeled SOAT1 inhibitors could support drug discovery and help diagnose SOAT1-related disorders, such as atherosclerosis. We synthesized two radiolabeled SOAT1 inhibitors, [C]PD-132301 and fluorine analogue [F]. Rat biodistribution studies were conducted with both agents and, as the most selective tracer, [C]PD-132301 was advanced to preclinical positron emission tomography studies in (atherosclerotic) ApoE mice. The uptake of [C]PD-132301 in SOAT1-rich tissue warrants further investigation into the compound as an atherosclerosis and adrenal imaging agent