OBJECTIVE:To determine which outcome measures could detect early progression of disease in school-age children with mild cystic fibrosis (CF) lung disease over a two-year time interval utilizing chest computed tomography (CT) scores, quantitative CT air trapping (QAT), and spirometric measurements. METHODS:Thirty-six school-age children with mild CF lung disease (median [interquartile range] age 12 [3.7] years; percent predicted forced expiratory volume in 1 second (ppFEV1 ) 99 [12.5]) were evaluated by serial spirometer-controlled chest CT scans and spirometry at baseline, 3-month, 1- and 2-years. RESULTS:No significant changes were noted at 3-month for any variable except for decreased ppFEV1 . Mucus plugging score (MPS) and QATA1andA2 increased at 1- and 2-years. The bronchiectasis score (BS), and total score (TS) were increased at 2-year. All variables tested with the exception of bronchial wall thickness score, parenchymal score (PS), and ppFEV1 , were consistent with longitudinal worsening of lung disease. Multivariate analysis revealed baseline PS, baseline TS, and 1-year changes in BS and air trapping score were predictive of 2-year changes in BS. CONCLUSIONS:MPS and QATA1-A2 were the most sensitive indicators of progressive childhood CF lung disease. The 1-year change in the bronchiectasis score had the most positive predictive power for 2-year change in bronchiectasis.

The disadvantage of visualizing tomography by slices is that an important attribute of the object, its volume, is not easily perceived or measured.In oncology this creates a problem, which is addressed here: if early detection and response to treatment are an important prognostic element, then volume is important.The literature has proposed surrogates to volume derived from measures on slices, but geometrically they are not well founded.Actual volume analysis is not complex, and the proposed method applies equally well to organs as to tumors.Volume based measures are more sensitive than individual SUV values, of which the commonly most used is the maximum Standardized Uptake Value (SUV m ).If the tumor volume is defined, it can be replaced by the total tumor SUV (SUV t ).If the metric for change is the ratio after/(before + after), in the patient population analyzed here, the SUV m metric averages 0.132 for response and 0.662 for progression, the total SUV t range is 0.069 to 0.734.In contrast to SUV t , SUV m is based on a weak sampling method since it is based on the value of a single voxel of more than 10 million.

The present paper is based on the observations that 1) there is reported variation in the specificities according to the type of tumor targeted (target) by FDG PET and 2) that while one can posit that the sensitivity of the tracer depends on the avidity for glucose and the plasma supply of the target, even so that the targeting cannot influence the avidity of unrelated tissues or lesions. The hypothesis to be tested is twofold: 1) patients imaged for different types of lesions could have a different prevalence of FDG avid tissues or lesions different from the target and 2) that the target lesions could be generally located in body location (sites) more likely to contain unrelated foci of increased uptake. Variance analysis shows that the sensitivity varies according to the target (p = 0.022), but not according to the location (p = 0.34); the specificity varies with the location (p = 0.0012) and the target (p = 0.05). Specificities are significantly different in different primary targets and target locations. The former is assumed to be due to different comorbidities in patients with different targets, the latter to the different locations of unrelated glucose avid organs or structures. Conclusion: When specificities are recorded or defined, the patient population characteristics and the organ or pathology of the false positives should also be described.

Purpose: Since HCC lesions are generally characterized by lower Hounsfield unit value (HU) values and higher tracer uptake (SUV or Standardized Uptake Values), we intended to determine if normalizing the SUV by the HU, for the lesion and normal liver would improve sensitivity and specificity. Material and Methods: Twenty-three consecutive patients with HCC diagnosed clinically or pathologically underwent C11-Acetate (C11-A) and F18-FDG (FDG) PET/CT imaging before surgery during a 424-day interval. After exclusion of treated or calcified lesions, 44 lesions are included in this study. The original metrics are the maximum SUV (SUVmax) and maximum or average HU (HUmax or HUmean) for lesions and normal liver. For the normal liver, an average SUV (SUVmean) was included. The derived values are the ratios of SUV/HU values. The efficacy is the fraction of outcomes of non-overlapping metrics between lesion and normal liver. Results: For FDG the efficacy is 0.489 for the lesions SUVmax versus normal liver SUVmax. For lesion SUVmax/HUmean versus normal liver SUVmax/HUmax, the efficacy is 1.00. For C11-A the corresponding values are 0.045 and 0.920. Conclusion: Normalizing SUV values for changes in HU values increases the contrast between normal liver and lesions. Analytical fusion can be very effective.

Venous thromboembolism (VTE) can present as deep vein thrombosis (DVT) and/or acute pulmonary embolism (PE). In fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT, 18F-FDG activity along the deep veins of the lower extremities (LE) is often observed and, unless it is associated with focal intense activity, is not considered abnormal. However, anecdotally it has been associated with the placement of an inferior vena cava filter. In this short paper we intend to investigate this association. We found 10 patients who were investigated in the vascular laboratory by means of either LE or upper-extremity duplex or a chest computed tomography with PE protocol, or who had undergone the placement of an inferior vena cava filter between 27 April 2010 and 7 January 2013 and who had also undergone one or more 18F-FDG-PET scan(s) that included the LE. Seventeen patients without venous 18F-FDG uptake were added as controls. 18F-FDG uptake visualized in the LE was scored as the number of positive LE veins and the extent of the radiotracer uptake. The time intervals between the VTE event and the 18F-FDG-PET scan(s) were recorded. The time intervals between the most remote and the closest 18F-FDG-PET before a VTE event averaged 79 ± 101 and 49 ± 82 days, respectively, and the closest and the most remote 18F-FDG-PET after the VTE event averaged 58 ± 50 and 122 ± 124 days. The extent of uptake in the LE veins averaged 7 ± 2 for the patients with an acute DVT on LE duplex and 5 ± 3 for those with negative or chronic DVT on LE duplex (P=nonsignificant). Two patients (n=3 and 10) were negative for VTE events and had an extent of 0. The number of positive events correlated slightly with the extent of venous uptake (r=0.69). The 17 control patients without venous uptake on 18F-FDG-PET had no history of VTE. There was an association between LE venous uptake of 18F-FDG and risk for VTE. The association was not related to the location of the VTE, nor to the timing of the VTE.

Fusion dual-tracer SPECT imaging enables physiological rather than morphological voxel-based partitioning and dosimetry for 90Y hepatic radioembolization (RE). We evaluated its prognostic value in a large heterogeneous cohort of patients with extensive hepatic malignancy.

The validation of medical imaging (processing and acquisition) can be achieved in multiple ways, somewhat influenced by the context. There are three traps to avoid: First reliance on ground truth requires the knowledge of it before the end of the trial, second comparison to gold standards cannot show improvement and finally one needs to deal with confirmation bias. In this paper we discuss those topics and alternative validation schemes.

1338 Learning Objectives 1. To review the epidemiology, pathology and patho-physiology of multiple myeloma. 2. To understand current staging classification and the roles of FDG-PET/CT in initial staging and therapy evaluation of multiple myeloma. 3. To understand the FDG-PET/CT evaluation of bone marrow background activity, focal bony lesions, extramedullary disease, infections, osteolytic lesions on CT scan and other pertinent findings for multiple myeloma patients with Bone Density, CT, MR, lab and pathological correlation. 4. To understand quantitative FDG-PET/CT parameters in relation of overall survival on patients with multiple myeloma. 5. To review FDG-PET/CT vs. NaF-PET/CT in the detection of myeloma-related bone lesions. Multiple myeloma is the second most common hematological malignancy after Hodgkin’s lymphoma, and the most common primary bone marrow malignancy. Until recently, conventional radiographic methods, and to some extent MRI have been employed as the mainstay of diagnosis, but whole-body FDG-PET/CT is rapidly emerging as the modality of choice for assessment of overall disease activity (skeletal and extramedullary), for treatment planning (both initially, and for subsequent response assessment), for follow up, and for differentiating among different plasma cell dyscrasia subtypes. In addition, PET provides prognostic information that is not achievable from structural modalities.

1357 Learning Objectives 1. Highlight the importance of SUV errors identification in FDG PET/CT imaging. 2. How to check the validity of the SUV result in FDG PET/CT studies. 3. Describe the different origins of the errors and the protocols to prevent SUV errors. 4. The educational review will help to provide a more reliable qualitative and quantitative interpretation of FDG PET/CT imaging. The imaging and the SUV values presented in front of you may not be the correct imaging with corrected SUVs. FDG PET/CT is often associated with SUV values errors and artifacts. If un-identified, these artifacts may lead to false positive, false negative interpretations and inaccurate quantitative data. It is extremely important for the PET/CT physician to become familiar with them so that they can be easily recognized, corrected and more importantly prevented.

Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver’s cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE.

Our purpose was to evaluate quantitative mid-treatment fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT scans in predicting the quantitative result of the end of treatment 18F-FDG PET/CT scan. With approval of Emory's Institutional Review Board, data were extracted from 273 existing 18F-FDG PET/CT scans of 143 pediatric patients performed for evaluation of lymphoma. The inclusion criteria were the availability of an initial staging scan (D0) and a mid-treatment scan after 1 to 3 cycles of chemotherapy (D1) and a post-treatment scan (D2). Absolute and relative changed of D1 compared to D0 were measured and their values in predicting D3 values were determined. Analysis was performed on a lesion basis (N=78) in 18 patients with an average of 4.3 lesions per patients. Results showed that the predictive value depended on the value selected as significant for the predictors (D1 SUV and D1 %SUV), and on the limit between negative and positive selected for the predicted value D2 SUV. If the maximum SUV<2.0 in D2 was the limit for negative, the negative predictive value if D1<4 was 0.84%. If positive was defined as D2>3.0, the positive predictive value of D1>4 was 100%. In that way outcome was predictable with absolute certainty in as many as 71% of the lesions with a single limit for D1 and D2. In conclusion, in this limited retrospective study the positive predictive value of the mid-treatment scan, was high for the post-treatment result for patient and lesion response seen on D2.

Planning hepatic Y-90 radioembolization activity requires balancing toxicity with efficacy. We developed a dual-tracer SPECT fusion imaging protocol that merges data on radioactivity distribution with physiologic liver mapping. Methods: Twenty-five patients with colorectal carcinoma and bilobar liver metastases received whole-liver radioembolization with resin microspheres prescribed as per convention (mean administered activity, 1.69 GBq). As part of standard treatment planning, all patients underwent SPECT imaging after intraarterial injection of 37 MBq of Tc-99m-macroaggregated albumin (Tc-99m-MAA) to simulate subsequent Y-90 distribution. Immediately afterward, patients received 185 MBq of labeled sulfur colloid (Tc-99m-SC) intravenously as a biomarker for normal hepatic reticuloendothelial function and SPECT was repeated. The SPECT images were coregistered and fused. A region-based method was used to predict the Y-90 radiation absorbed dose to functional liver tissue (D-FL) by calculation of Tc-99m-MAA activity in regions with Tc-99m-SC uptake. Similarly, the absorbed dose to tumor (D-T) was predicted by calculation of Tc-99m-MAA activity in voxels without Tc-99m-SC uptake. Laboratory data and radiographic response were measured for 3 mo, and the survival of patients was recorded. SPECT-based D-T and D-FL were correlated with parameters of toxicity and efficacy. Results: Toxicity, as measured by increase in serum liver enzymes, correlated significantly with SPECT-based calculation of D-FL at all time points (P < 0.05) (mean D-FL, 27.9 Gy). Broad biochemical toxicity (>50% increase in all liver enzymes) occurred at a D-FL of 24.5 Gy and above. In addition, in uni- and multivariate analysis, SPECT-based calculation of D-T (mean D-T, 44.2 Gy) correlated with radiographic response (P < 0.001), decrease in serum carcinoembryonic antigen (P < 0.05), and overall survival (P < 0.01). The cutoff value of D-T for prediction of 1-y survival was 55 Gy (area under the receiver-operating-characteristic curve = 0.86; P < 0.01). Patients who received a D-T of more than 55 Gy had a median survival of 32.8 mo, compared with 7.2 mo in patients who received less (P < 0.05). Conclusion: Dual-tracer Tc-99m-MAA-Tc-99m-SC fusion SPECT offers a physiology-based imaging tool with significant prognostic power that may lead to improved personalized activity planning.

An observational finding found a large variation in the brain SUV in patients with multiple myeloma undergoing PET/CT.The first hypothesis considered a toxic effect of chemotherapeutic agents, but no correlation was found with hematological signs of toxicity.Low brain FDG uptake has been described with anesthesia, but this was not relevant in this case.An alternative is the presence of a large FDG avid mass, but that was excluded.Since there was a question of chemotherapy toxicity, the metrics used for comparison were Hemoglobin levels (Hgb, g/dl), Erythrocyte count (RBC, M/μL), Lymphocytes absolute counts (Lymph#, K/μL) and % (lymph, %), Granulocytes Neutrophils, K/μL), age and C-reactive protein levels (CRP, g/L).The liver SUV (standardized uptake value) was included to eliminate unexpected global effects on the SUV values, since FDG uptake is a competitive system with a single source (plasma FDG levels).There was in fact no correlation between brain SUV and hepatic SUV, eliminating the so-called super scan effect.Further analysis, however, revealed a strong positive correlation with hemoglobin or RBC levels, but an inverse effect with Neutrophils, C-reactive proteins and age (in years).The results suggest that brain metabolism strongly depends on oxygen supply and may be depressed by general inflammatory diseases and independently with age.If the variation of glucose metabolism correlates with cognitive deficits (CD), considering general measures of good health may be a first step for relief of age related CD.

While decreased ATP production and redox imbalance are central to mitochondrial disease pathogenesis, efforts to develop effective treatments have been hampered by the lack of imaging markers of oxidative stress. In this study we wished to determine if Tc99m-HMPAO, a SPECT imaging marker of cerebral blood flow and glutathione/protein thiol content, could be used to monitor the effect(s) of EPI-743, an oral redox modulating, para-benzoquinone based therapeutic for mitochondrial disease. We hypothesized that treatment changes in HMPAO uptake would be inversely proportional to changes in oxidative stress within the brain and directly correlate to clinical response to EPI-743 therapy. Twenty-two patients with mitochondrial disease were treated with EPI-743. Each underwent baseline and 3-month Tc99m-HMPAO SPECT scanning along with clinical/neurologic evaluations. Diseases treated were: Leigh syndrome (n=7), polymerase γ deficiency (n=5), MELAS (n=5), Friedreich ataxia (n=2), Kearns-Sayre syndrome, Pearson syndrome, and mtDNA depletion syndrome. Neuro-anatomic uptake analyses of HMPAO were performed with NeuroGam™ (Segami Corp.) statistical software and clinical response was assessed by the Newcastle Paediatric Mitochondrial Disease Scale or Newcastle Mitochondrial Disease Adult Scale depending on patient age. For all 22 patients there was a significant linear correlation between the change in cerebellar uptake of HMPAO and the improvement in Newcastle score (r=0.623, **p=0.00161). The MELAS subgroup showed a significant relationship of whole brain uptake (n=5, r=0.917, *p=0.028) to improvement in Newcastle score. We conclude that Tc99m-HMPAO SPECT scanning has promise as a general marker of the oxidative state of the brain and its response to redox modulating therapies. Further studies will be needed to confirm these findings in a more homogenous study population.

This study aims to evaluate 64Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.

1697 Objectives In this study we attempted to predict human dosimetry for a novel antibody based PET tracer, Cu-DOTA-rituximab prior to clinical translation. Methods To validate the PET tracer multiple radiolabeling, Quality assurance (QA), and imaging experiments were carried out in three groups of transgenic mice (CD20TM) that express the human CD20 on their B cells. The study groups of mice are as follows; a) control (nude mice, n=2) that received 7.4 MBq Cu-rituximab, b) with pre-dose (CD20TM, n=6): received 2 mg/kg pre-dose of cold rituximab prior to 7.4 MBq Cu-DOTA-rituximab, and c) without pre-dose (CD20TM, n=6) 7.4 MBq Cu-DOTA-rituximab. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h) post-injection of Cu-DOTA-rituximab. Organs were delineated on small animal PET and computed tomography (CT) images. The OLINDA/EXM application was used to determine the human equivalent dose for individual organs. Results QA of tracer showed specific activity of 545 ± 38.91 TBq/mol, RCY >80%, IR >80% and purity >95%. At 24 h, spleen uptake of PET tracer in %ID/g (mean ± STD) was 1.76 ± 0.43 and 16.5 ± 0.45 with and without pre-dosing, respectively (P Conclusions Pre-clinical evaluation of Cu-rituximab with huCD20TM showed that this novel PET tracer is able to specifically image huCD20. Human dosimetry of PET tracer was estimated for clinical translation and an IND has been obtained (IND #104995). Research Support ICMIC P50 - CA11474