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Imaging of cholesterol use is possible with the

Supplementary Table S4.

Purpose: While hyperthermia is an effective adjuvant treatment to radiotherapy, we do not completely understand the nature of the response heterogeneity.Experimental Design: We performed gene expression analysis of 22 spontaneous canine sarcomas before and after the first hyperthermia treatment administered as an adjuvant to radiotherapy. In parallel, diffusion-weighted MRI (DWI) was done prior to the treatment course and at the end of therapy.Results: From the integrative analysis of gene expression and DWI, we identified significant correlation between tumor responses with genes involved in VEGF signaling, telomerase, DNA repair, and inflammation. The treatment-induced changes in gene expression identified 2 distinct tumor subtypes with significant differences in their gene expression and treatment response, as defined by changes in DWI. The 2 tumor subtypes could also be readily identified by pretreatment gene expression. The tumor subtypes, with stronger expression response and DWI increase, had higher levels of HSP70, POT1, and centrosomal proteins, and lower levels of CD31, vWF, and transferrin. Such differential gene expression between the 2 subtypes was used to interrogate connectivity map and identify linkages to an HSP90 inhibitor, geldanamycin. We further validated the ability of geldanamycin to enhance cell killing of human tumor cells with hyperthermia and radiotherapy in clonogenic assays.Conclusions: To our knowledge, this is one of the first successful attempts to link changes in gene expression and functional imaging to understand the response heterogeneity and identify compounds enhancing thermoradiotherapy. This study also demonstrates the value of canine tumors to provide information generalizable to human tumors. Clin Cancer Res; 17(8); 2549–60. ©2011 AACR.

Supplementary Data from Dynamic Contrast-enhanced Magnetic Resonance Imaging as a Predictor of Clinical Outcome in Canine Spontaneous Soft Tissue Sarcomas Treated with Thermoradiotherapy

Supplementary Figures S1-S7.

Purpose: This study tests whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters obtained from canine patients with soft tissue sarcomas, treated with hyperthermia and radiotherapy, are predictive of therapeutic outcome.Experimental Design: Thirty-seven dogs with soft tissue sarcomas had DCE-MRI done before and following the first hyperthermia. Signal enhancement for tumor and reference muscle were fitted empirically, yielding a washin/washout rate for the contrast agent and tumor area under the signal enhancement curve (AUC) calculated from 0 to 60 seconds, 90 seconds, and the time of maximal enhancement in the reference muscle. These parameters were then compared with local tumor control, metastasis-free survival, and overall survival.Results: Pretherapy rate of contrast agent washout was positively predictive of improved overall and metastasis-free survival with hazard ratio of 0.67 (P = 0.015) and 0.68 (P = 0.012), respectively. After the first hyperthermia washin rate, AUC60, AUC90, and AUCt-max were predictive of improved overall and metastasis-free survival with hazard ratio ranging from 0.46 to 0.53 (P < 0.002) and 0.44 to 0.55 (P < 0.004), respectively. DCE-MRI parameters were compared with extracellular pH and 31P MR spectroscopy results (previously published) in the same patients showing a correlation. This suggested that an increase in perfusion after therapy was effective in eliminating excess acid from the tumor.Conclusions: This study shows that DCE-MRI has utility predicting overall and metastasis-free survival in canine patients with soft tissue sarcomas. To our knowledge, this is the first time that DCE-MRI parameters are predictive of clinical outcome for soft tissue sarcomas.

For 45 years, efforts to prepare a fluorinated analogue of the scintiscanning/SPECT agent 6-(iodomethyl)-19-norcholest-5(10)-en-3-ol (NP-59) for development of a PET imaging agent have failed due to undesired elimination reactions and unexpected rearrangements observed­ while utilizing a wide variety of fluorinating conditions (e.g., cesium­ fluoride, silver fluoride, (2-chloro-1,1,2-trifluoroethyl)diethylamine (FAR), diethylaminosulfur trifluoride (DAST), and hexa­fluoro­propene diethylamine FPA). Herein, we report the full synthesis of NP-59, followed by the four-step synthesis of 6-(fluoromethyl)-19-norcholest-5(10)-en-3-ol (FNP-59) using a recently developed mild fluorinating reagent, less prone to producing elimination reactions in the preparation of primary fluorides, TBAF(pinacol)2, with an overall yield of 16% (four steps). Also included is an evaluation of the TBAF(pinacol)2 reagent on eight test substrates to investigate its scope.

A simple technique for the preparation of [18F]HF has been developed and applied to the generation of an [18F]FeF species for opening sterically hindered epoxides. This method has been successfully employed to prepare four drug-like molecules, including 5-[18F]fluoro-6-hydroxy-cholesterol, a potential adrenal/endocrine PET imaging agent. This easily automated one-pot procedure produces sterically hindered fluorohydrin PET imaging agents in good yields and high molar activities.

The purpose of this review is to summarise a literature survey on thermal thresholds for tissue damage. This review covers published literature for the consecutive years from 2002-2009. The first review on this subject was published in 2003. It included an extensive discussion of how to use thermal dosimetric principles to normalise all time-temperature data histories to a common format. This review utilises those same principles to address sensitivity of a variety of tissues, but with particular emphasis on brain and testis. The review includes new data on tissues that were not included in the original review. Several important observations have come from this review. First, a large proportion of the papers examined for this review were discarded because time-temperature history at the site of thermal damage assessment was not recorded. It is strongly recommended that future research on this subject include such data. Second, very little data is available examining chronic consequences of thermal exposure. On a related point, the time of assessment of damage after exposure is critically important for assessing whether damage is transient or permanent. Additionally, virtually no data are available for repeated thermal exposures which may occur in certain recreational or occupational activities. For purposes of regulatory guidelines, both acute and lasting effects of thermal damage should be considered.

Resistance of hypoxic solid tumor niches to chemotherapy and radiotherapy remains a major scientific challenge that calls for conceptually new approaches. Here we exploit a hitherto unrecognized ability of sickled erythrocytes (SSRBCs) but not normal RBCs (NLRBCs) to selectively target hypoxic tumor vascular microenviroment and induce diffuse vaso-occlusion. Within minutes after injection SSRBCs, but not NLRBCs, home and adhere to hypoxic 4T1 tumor vasculature with hemoglobin saturation levels at or below 10% that are distributed over 70% of the tumor space. The bound SSRBCs thereupon form microaggregates that obstruct/occlude up to 88% of tumor microvessels. Importantly, SSRBCs, but not normal RBCs, combined with exogenous prooxidant zinc protoporphyrin (ZnPP) induce a potent tumoricidal response via a mutual potentiating mechanism. In a clonogenic tumor cell survival assay, SSRBC surrogate hemin, along with H(2)O(2) and ZnPP demonstrate a similar mutual potentiation and tumoricidal effect. In contrast to existing treatments directed only to the hypoxic tumor cell, the present approach targets the hypoxic tumor vascular environment and induces injury to both tumor microvessels and tumor cells using intrinsic SSRBC-derived oxidants and locally generated ROS. Thus, the SSRBC appears to be a potent new tool for treatment of hypoxic solid tumors, which are notable for their resistance to existing cancer treatments.

[Image: see text] PD-132301, an inhibitor of sterol O-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, [(11)C]PD-132301 and fluorine analogue [(18)F]1. Rat biodistribution studies were conducted with both agents and, as the most selective tracer, [(11)C]PD-132301 was advanced to preclinical positron emission tomography studies in (atherosclerotic) ApoE(–/–) mice. The uptake of [(11)C]PD-132301 in SOAT1-rich tissue warrants further investigation into the compound as an atherosclerosis and adrenal imaging agent.

PURPOSE: To assess associations between parotid gland PET biomarkers and late radiation-induced xerostomia, and to validate improvement of xerostomia predictive models by adding pre-treatment PET features to models based on dose and pre-treatment xerostomia. MATERIALS AND METHODS: Intensity PET features from 47 patients treated on institutional prospective clinical trials for HPV-associated oropharyngeal squamous cell carcinoma with uniform chemoRT were analyzed. Associations between 90(th) percentile of the parotid gland standardized uptake values (P90) from pre-treatment and post-treatment PET scans, mean parotid gland doses, and late xerostomia defined by the Xerostomia Questionnaire (XQ) and salivary flow rates were quantified. Multivariate analysis was applied for dose and PET features using penalized logistic regression for feature selection and generation of predictive models using the LASSO technique, and optimism bias was estimated by bootstrap resampling. RESULTS: Significant associations between late xerostomia and both mean parotid gland dose and P90 were demonstrated, and were generally stronger for post-treatment PET scans. The addition of P90 from pre-treatment PET scans improved the prediction model for late moderate or severe xerostomia compared to the base model, from AUC=0.74 to 0.78 (p-value

Radiolabeled erythrocytes have multiple applications in nuclear medicine, including blood pool imaging. Historically they have been labeled with SPECT radionuclides. A PET blood pool imaging agent is highly desirable as it would improve clinical applications with better image quality and resolution, higher sensitivity, and dynamic scanning capabilities. With the coming of age of modern 68Ge/68Ga generator systems, gallium-68 is now widely accessible. In this paper we describe an updated method for the preparation of 68Ga-labeled erythrocytes and their preliminary use in rodent blood pool imaging. A novel automated synthesis of [68Ga]oxine using a 68Ga/68Ge generator and automated synthesis module is reported. [68Ga]Oxine was synthesized in 50 ± 5% (n = 3) non-decay corrected radiochemical yield and >99% radiochemical purity. Rat and human erythrocytes were successfully labeled with the complex in 42% RCY, and the 68Ga-labeled erythrocytes have been shown to clearly image the blood pool in a healthy rat. Human erythrocytes labelled with [68Ga]oxine were shown to be viable up to 2 hours post-labelling, and washout of the radiolabel was minimal up to 1 hour post-labelling. Further optimization of the labeling method to translate for use in human cardiac and oncologic blood pool PET imaging studies, is underway.

In addition to gastroenteropancreatic neuroendocrine neoplasms, a wide variety of tumors express somatostatin receptors. Somatostatin receptor imaging, heavily utilized in neuroendocrine oncology, may also have utility in the diagnosis of other neoplasms and raises the possibility of potential therapeutic options. We describe the case of a 60-year-old man who underwent 68Ga-DOTATATE PET/CT, demonstrating an avid invasive pituitary macroadenoma. This mass was persistent and refractory despite traditional treatment options. Because of the avidity, 177Lu-DOTATATE therapy was offered, although not ultimately performed, demonstrating a potential treatment for challenging cases utilizing the principles of theranostics.

Purpose Blood 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.

Adrenal lesions are routinely encountered incidentally in clinical practice. Although most of these lesions are benign, malignancy needs to be excluded. Therefore, the initial clinical workup is to exclude aggressive characteristics suggesting malignancy and to identify characteristics predictive of the most common benign lesion, an adrenal adenoma. Predicting a benign adenoma using a variety of imaging modalities has been widely studied using unenhanced computed tomography (CT), contrast enhanced CT, and magnetic resonance (MR) imaging. This review article describes the currently used imaging protocols and clinical interpretation criteria of common adrenal lesions. An adenoma can be predicted if a homogenous soft tissue adrenal mass demonstrates low attenuation (upper threshold value of 10 Hounsfield Units) on unenhanced CT, demonstrates an absolute enhancement washout of ≥ 60% and/or relative enhancement washout of ≥ 40% on adrenal washout contrast enhanced CT, or demonstrates signal loss in opposed-phased MR imaging. If an adrenal adenoma cannot be predicted based upon these criteria, the lesion should be evaluated for other imaging characteristics that suggest a specific pathology, such as an adrenal cyst or myelolipoma. Although nonspecific and with limitations, 18F-fluorodeoxyglucose (FDG) PET/CT has a potential role for differentiating benign from malignant lesions based upon the amount of radiopharmaceutical uptake with malignant lesions generally having greater uptake. If clinical and/or hormonal screening suggests a pheochromocytoma, consideration can be given to 18F-dihydroxyphenylalanine (DOPA) or 123I-metaiodobenzylguanidine (MIBG) in addition to CT and MR. Finally, this review proposes a diagnostic work-up strategy for routine use in clinical practice.

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.

Sites of infection and inflammation can be misleading in oncology PET/CT imaging because these areas commonly show 18F-FDG activity. Caution in the interpretation must be taken to avoid the misdiagnosis of malignancy. Utilization of both CT findings as well as patient history can help differentiate benign infectious and inflammatory processes from malignancy, although occasionally additional work-up may be required. This article discusses the mechanism of 18F-FDG uptake in infection and inflammation with illustrative examples.

A simple technique for the preparation of [(18)F]HF has been developed and applied to the generation of an [(18)F]FeF species for opening sterically hindered epoxides. This method has been successfully employed to prepare four drug-like molecules, including 5-[(18)F]fluoro-6-hydroxy-cholesterol, a potential adrenal/endocrine PET imaging agent. This easily automated one-pot procedure produces sterically hindered fluorhydrin PET imaging agents in good yields and high molar activities.

Purpose: Hyperglycemia affects FDG uptake in the brain, potentially emulating Alzheimer’s disease in normal individuals. This study investigates global and regional cerebral FDG uptake as a function of plasma glucose in a cohort of patients. Methods: 120 consecutive male patients with FDG PET/CT for initial oncologic staging (July–Dec 2015) were reviewed. Patients with dementia, cerebrovascular accident, structural brain lesion, prior oncology treatment or high metabolic tumor burden (recently shown affecting brain FDG uptake) were excluded. 53 (24 nondiabetic) eligible patients (age 65.7 ± 2.8 mean ± SE) were analyzed with parametric computer software, MIMneuro™. Regional Z-scores were evaluated as a function of plasma glucose and age using multi variable linear mixed effects models with false discovery analysis adjusting for multiple comparisons. If the regression slope was significantly (p

Purpose Dose to normal lung has commonly been linked with radiation-induced lung toxicity (RILT) risk, but incorporating functional lung metrics in treatment planning may help further optimize dose delivery and reduce RILT incidence. The purpose of this study was to investigate the impact of the dose delivered to functional lung regions by analyzing perfusion (Q), ventilation (V), and combined V/Q single-photon-emission computed tomography (SPECT) dose-function metrics with regard to RILT risk in patients with non-small cell lung cancer (NSCLC) patients who received radiation therapy (RT). Methods and Materials SPECT images acquired from 88 patients with locally advanced NSCLC before undergoing conventionally fractionated RT were retrospectively analyzed. Dose was converted to the nominal dose equivalent per 2 Gy fraction, and SPECT intensities were normalized. Regional lung segments were defined, and the average dose delivered to each lung region was quantified. Three functional categorizations were defined to represent low-, normal-, and high-functioning lungs. The percent of functional lung category receiving ≥20 Gy and mean functional intensity receiving ≥20 Gy (iV20) were calculated. RILT was defined as grade 2+ radiation pneumonitis and/or clinical radiation fibrosis. A logistic regression was used to evaluate the association between dose-function metrics and risk of RILT. Results By analyzing V/Q normalized intensities and functional distributions across the population, a wide range in functional capability (especially in the ipsilateral lung) was observed in patients with NSCLC before RT. Through multivariable regression models, global lung average dose to the lower lung was found to be significantly associated with RILT, and Q and V iV20 were correlated with RILT when using ipsilateral lung metrics. Through a receiver operating characteristic analysis, combined V/Q low-function receiving ≥20 Gy (low-functioning V/Q20) in the ipsilateral lung was found to be the best predictor (area under the curce: 0.79) of RILT risk. Conclusions Irradiation of the inferior lung appears to be a locational sensitivity for RILT risk. The multivariable correlation between ipsilateral lung iV20 and RILT, as well as the association of low-functioning V/Q20 and RILT, suggest that irradiating low-functioning regions in the lung may lead to higher toxicity rates.

Graphical Abstract, Rationale & Objective Recent evidence suggests that adults with cerebral palsy have an elevated risk for developing advanced chronic kidney disease (CKD). To develop effective interventions, the objective was to identify whether demographics and preexisting medical conditions are risk factors for advanced CKD among adults with cerebral palsy. Study Design Retrospective cohort study. Setting & Participants Data were from the Optum Clinformatics Data Mart. Adults 18 years or older with cerebral palsy and without advanced CKD (CKD stage 4 or later) were identified from 2013 and subsequently followed up from January 1, 2014, to the development of advanced CKD, death, loss to follow-up, or end of the study period (December 31, 2017), whichever came first. Diagnostic, procedure, and diagnosis-related group codes were used to identify cerebral palsy, incident cases of advanced CKD, comorbid intellectual disability, and 10 preexisting medical conditions. Exposures Demographic variables and 10 preexisting medical conditions: CKD stages 1-3, hypertension, diabetes, heart and cerebrovascular disease, non-CKD urologic conditions, bowel conditions, respiratory disease, skeletal fragility, arthritis, and dysphagia. Outcome Incidence of advanced CKD. Analytic Approach Crude incidence rate (IR) of advanced CKD and IR ratios with 95% CIs were estimated. Cox proportional hazards regression models that were adjusted for demographics, intellectual disability, and preexisting medical conditions were used to evaluate the adjusted independent effect of predictor variables. Results 237 of the 8,011 adults with cerebral palsy developed advanced CKD during follow-up (IR, 10.16/1,000 person years; 95% CI, 8.87-11.46). In the crude analysis, all preexisting medical conditions were associated with an elevated IR and IR ratio of advanced CKD. In the fully adjusted Cox proportional hazards regression model, the HR was elevated for older age, CKD stages 1-3 (HR, 3.32; 95% CI, 2.39-4.61), diabetes (HR, 2.69; 95% CI, 2.03-3.57), hypertension (HR, 1.54; 95% CI, .10-2.16), heart and cerebrovascular disease (HR, 1.53; 95% CI, 1.12-2.07), and non-CKD urologic conditions (HR, 1.39; 95% CI, 1.05-1.84). Limitations Private insurance database, short follow-up period, and lack of laboratory values, such as albuminuria/proteinuria. Conclusions Advanced CKD was common among adults with cerebral palsy and its development was associated with both traditional and nontraditional urologic risk factors.

OBJECTIVE: Frostbite is a localized cold-thermal injury resulting from prolonged exposure of flesh to freezing and near freezing temperatures. The depth and extent of frostbite injuries are not easily assessed, from a clinical standpoint, at the time of injury making it challenging to plan appropriate management and treatment. METHODS: A review of the literature of management of cold-related injuries and retrospective case review of the imaging and clinical course of frostbite injury. RESULTS: Bone scintigraphy with single photon emission computed tomography (SPECT)/CT was performed in the acute and subacute course of frostbite injuries, subsequently leading to earlier definitive management and shorter hospital stay. CONCLUSION: Multiphase technetium-99m-methylenediphosphonate ((99)mTc-MDP) bone scintigraphy with SPECT/CT can expedite clinical management of frostbite injuries by determining the extent of injury and can accurately predict the level of amputation if needed. ADVANCES IN KNOWLEDGE: SPECT/CT is underutilized at many facilities but can have a profound and immediate impact on clinical management of patients with frostbite when used in combination with physiological bone scan imaging.

Painful osseous metastasis resulting from castration-resistant prostate carcinoma is a common clinical problem. Historically, nuclear medicine offered several palliative beta-emitting radiopharmaceuticals targeting the skeleton with the goal of decreasing pain. However, these have largely been replaced by the alpha-emitting agent 223radium (Ra). 223Ra received Food and Drug Administration approval in 2013 for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases without visceral metastases. 223Ra offers an improved therapeutic profile due to its alpha-particle emissions resulting in a relatively higher linear energy transfer and lower particle range compared with beta-emitters. 223Ra also has demonstrated to increase overall survival in patients and to delay adverse skeletal events. Running a successful clinical nuclear therapy program with Ra requires a multidisciplinary team approach and this article suggests an implementation strategy from the authors' institution. Potential new nuclear radiopharmaceuticals still under investigation offering the future possibility of radioligand therapy are also discussed briefly.

Vesicoureteral reflux after renal transplantation is associated with increase risk of urinary tract infections, renal scarring, and graft failure. We describe a case of a 46-year-old woman with 2 transplant kidneys, one functioning and another nonfunctioning, presenting with pelvic pain after a bilateral periureteral bulking procedure. Diuretic renography was performed to exclude iatrogenic ureteral obstruction. This showed a normally functioning transplant kidney without obstruction and subsequent vesicoureteral reflux into the collecting system of the nonfunctioning transplant kidney. This inadvertent indirect nuclear cystogram illustrates an unusual imaging presentation of a common disease process requiring further treatment.

Purpose To examine the effect metabolic burden (tumor and/or cardiac myocyte uptake) has on fluorine 18 fluorodeoxyglucose (FDG) distribution in organs and tissues of interest. Materials and Methods Positron emission tomographic (PET)/computed tomographic (CT) scans at the Ann Arbor Veterans Affairs hospital from January to July 2015 were reviewed. A total of 107 scans (50 patients; mean age, 64.3 years ± 13.2 [standard deviation]) had metabolic tissue burden assessed by using total lesion glycolysis (TLG) obtained from autosegmentation of the tumor and/or cardiac tissue. Standardized uptake value (SUV) and subsequent normalized SUV uptake in target organs and tissues were compared with 436 FDG PET/CT scans previously reported in 229 patients as a function of TLG to describe the effect(s) that metabolic burden has on reference tissue (blood pool, liver, and brain) FDG uptake. Subsequent regression by using linear mixed-effects models was used. If the slope of the regression was significantly (P.05) different than zero, then an effect from TLG was present. Results There was a negative inverse relationship (P.0001) between FDG uptake within reference tissues (blood pool, liver, and brain) and TLG in comparison to the study population at similar blood glucose levels. This TLG effect was no longer statistically significant (P.05) when FDG uptake was normalized to a reference tissue (eg, blood pool or liver). Conclusion Metabolic tissue burden can have a significant effect on SUV measurements for PET imaging. This effect can be mitigated by normalizing FDG uptake to a reference tissue.

To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in 18F-FDG-PET scan. 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, 18F-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). 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 200 mg/dl had significantly lower SUVmax. If BGL is lower than 200 mg/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.

In addition to nuclear cardiac and breast imaging, Tc-sestamibi scintigraphy is often used to localize parathyroid adenomas. F- fluorodeoxyglucose (FDG) PET is heavily utilized in oncology, although its use in identifying parathyroid adenomas is limited. We describe a case of a 57-year-old woman who underwent parathyroid scintigraphy and F-FDG PET/CT in the same week due to hyperparathyroidism and an enlarging breast mass, respectively. A right paratracheal mediastinal mass that otherwise would be suspicious for nodal metastases by CT alone was correctly identified to be an ectopic parathyroid adenoma using a combination of the nuclear medicine studies performed.

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.

Blood glucose is routinely measured prior to436 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.We 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.The 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.

Classification of thermal injury is typically accomplished either through the use of an equivalent dosimetry method (equivalent minutes at 43 °C, CEM43 °C) or through a thermal-injury-damage metric (the Arrhenius method). For lower-temperature levels, the equivalent dosimetry approach is typically employed while higher-temperature applications are most often categorized by injury-damage calculations. The two methods derive from common thermodynamic/physical chemistry origins. To facilitate the development of the interrelationships between the two metrics, application is made to the case of skin burns. This thermal insult has been quantified by numerical simulation, and the extracted time-temperature results served for the evaluation of the respective characterizations. The simulations were performed for skin-surface exposure temperatures ranging from 60 to 90 °C, where each surface temperature was held constant for durations extending from 10 to 110 s. It was demonstrated that values of CEM43 at the basal layer of the skin were highly correlated with the depth of injury calculated from a thermal injury integral. Local values of CEM43 were connected to the local cell survival rate, and a correlating equation was developed relating CEM43 with the decrease in cell survival from 90% to 10%. Finally, it was shown that the cell survival/CEM43 relationship for the cases investigated here most closely aligns with isothermal exposure of tissue to temperatures of ~50 °C.

To determine for expert and novice radiologists repeatability of major diagnostic features and scoring systems (ie, Liver Imaging Reporting and Data System [LI-RADS], Organ Procurement and Transplantation Network [OPTN], and American Association for the Study of Liver Diseases [AASLD]) for hepatocellular carcinoma (HCC) by using magnetic resonance (MR) imaging.Institutional review board approval was obtained and patient consent was waived for this HIPAA-compliant, retrospective study. The LI-RADS discussed in this article refers to version 2013.1. Ten blinded readers reviewed 100 liver MR imaging studies that demonstrated observations preliminarily assigned LI-RADS scores of LR1-LR5. Diameter and major HCC features (arterial hyperenhancement, washout appearance, pseudocapsule) were recorded for each observation. LI-RADS, OPTN, and AASLD scores were assigned. Interreader agreement was assessed by using intraclass correlation coefficients and κ statistics. Scoring rates were compared by using McNemar test.Overall interreader agreement was substantial for arterial hyperenhancement (0.67 [95% confidence interval {CI}: 0.65, 0.69]), moderate for washout appearance (0.48 [95%CI: 0.46, 0.50]), moderate for pseudocapsule (0.52 [95% CI: 050, 0.54]), fair for LI-RADS (0.35 [95% CI: 0.34, 0.37]), fair for AASLD (0.39 [95% CI: 0.37, 0.42]), and moderate for OPTN (0.53 [95% CI: 0.51, 0.56]). Agreement for measured diameter was almost perfect (range, 0.95-0.97). There was substantial agreement for most scores consistent with HCC. Experts agreed significantly more than did novices and were significantly more likely than were novices to assign a diagnosis of HCC (P.001).Two of three major features for HCC (washout appearance and pseudocapsule) have only moderate interreader agreement. Experts and novices who assigned scores consistent with HCC had substantial but not perfect agreement. Expert agreement is substantial for OPTN, but moderate for LI-RADS and AASLD. Novices were less consistent and less likely to diagnose HCC than were experts.

Sites of infection and inflammation can be misleading in oncology PET/CT imaging because these areas commonly show 18F-FDG activity. Caution in the interpretation must be taken to avoid the misdiagnosis of malignancy. Utilization of both CT findings as well as patient history can help differentiate benign infectious and inflammatory processes from malignancy, although occasionally additional work-up may be required. This article discusses the mechanism of 18F-FDG uptake in infection and inflammation with illustrative examples.

During hyperthermia (HT), the therapeutic response of tumours varies substantially within the target temperature range (39-43 °C). Current thermometry methods are either invasive or measure only temperature change, which limits the ability to study tissue responses to HT. This study combines manganese-containing low temperature sensitive liposomes (Mn-LTSL) with proton resonance frequency shift (PRFS) thermometry to measure absolute temperature in tumours with high spatial and temporal resolution using MRI.Liposomes were loaded with 300 mM MnSO(4). The phase transition temperature (T(m)) of Mn-LTSL samples was measured by differential scanning calorimetry (DSC). The release of manganese from Mn-LTSL in saline was characterised with inductively coupled plasma atomic emission spectroscopy. A 2T GE small animal scanner was used to acquire dynamic T1-weighted images and temperature change images of Mn-LTSL in saline phantoms and fibrosarcoma-bearing Fisher-344 rats receiving hyperthermia after Mn-LTSL injection.The T(m) of Mn-LTSL in rat blood was 42.9 ± 0.2 °C (DSC). For Mn-LTSL samples (0.06 mM-0.5 mM Mn(2+) in saline) heated monotonically from 30 °C to 50 °C, a peak in the rate of MRI signal enhancement occurred at 43.1° ± 0.3 °C. The same peak in signal enhancement rate was observed during heating of fibrosarcoma tumours (N = 3) after injection of Mn-LTSL, and the peak was used to convert temperature change images into absolute temperature. Accuracies of calibrated temperature measurements were in the range 0.9-1.8 °C.The release of Mn(2+) from Mn-LTSL affects the rate of MR signal enhancement which enables conversion of MRI-based temperature change images to absolute temperature.

Intravenous gadoxetate disodium can result in acute transient dyspnea that can have a deleterious effect on arterial phase MR image quality and occurs significantly more often than with intravenous gadobenate dimeglumine.

Adrenocortical cancer (ACC) is an uncommon primary neoplasm of the adrenal cortex with dismal prognosis. It often presents with symptoms and signs of adrenal cortical hormone hypersecretion and abdominal mass effect or is incidentally detected as an adrenal mass on imaging performed for other indications. Endocrine evaluation, comprehensive staging, and meticulous resection are crucial to ensure the best possible outcome. Despite extensive initial surgical resection, local and distant metastases are not uncommon with disappointing 5-year survival, although progress is being made at high-volume centers. Accurate restaging of recurrent disease is important to guide further management. Mitotane, external beam radiation and chemotherapy, and newer anticancer systemic treatments are used as adjunctives for inoperable disease and distant metastases. Contrast-enhanced CT and MRI are first-line imaging modalities for evaluation of ACC to characterize adrenal masses and to determine tumor resectability. Emerging literature supports F-FDG PET/CT use to determine the malignant potential of adrenal masses. In patients with a diagnosis of ACC, FDG PET/CT is sensitive for detecting metastatic disease, and its tumor accumulation has been correlated to pathology, Weiss scores, and prognosis. Metomidate, labeled with C for PET or with I for SPECT/CT, allows characterization of an adrenal mass as being of adrenocortical origin with high specificity. Taking advantage of its adrenocortical avidity, metomidate has been labeled with I for radionuclide therapy in a subset of ACC. In this review, we describe how nuclear medicine imaging, and specifically PET, can assist surgical management of ACC.

Purpose: While hyperthermia is an effective adjuvant treatment to radiotherapy, we do not completely understand the nature of the response heterogeneity. Experimental Design: We performed gene expression analysis of 22 spontaneous canine sarcomas before and after the first hyperthermia treatment administered as an adjuvant to radiotherapy. In parallel, diffusion-weighted MRI (DWI) was done prior to the treatment course and at the end of therapy. Results: From the integrative analysis of gene expression and DWI, we identified significant correlation between tumor responses with genes involved in VEGF signaling, telomerase, DNA repair, and inflammation. The treatment-induced changes in gene expression identified 2 distinct tumor subtypes with significant differences in their gene expression and treatment response, as defined by changes in DWI. The 2 tumor subtypes could also be readily identified by pretreatment gene expression. The tumor subtypes, with stronger expression response and DWI increase, had higher levels of HSP70, POT1, and centrosomal proteins, and lower levels of CD31, vWF, and transferrin. Such differential gene expression between the 2 subtypes was used to interrogate connectivity map and identify linkages to an HSP90 inhibitor, geldanamycin. We further validated the ability of geldanamycin to enhance cell killing of human tumor cells with hyperthermia and radiotherapy in clonogenic assays. Conclusions: To our knowledge, this is one of the first successful attempts to link changes in gene expression and functional imaging to understand the response heterogeneity and identify compounds enhancing thermoradiotherapy. This study also demonstrates the value of canine tumors to provide information generalizable to human tumors. Clin Cancer Res; 17(8); 2549–60. ©2011 AACR.