68Ga-DOTATATE PET/CT: The Optimum Standardized Uptake Value (SUV) Internal Reference.

RATIONALE AND OBJECTIVES: Standardized Uptake Value (SUV) is an important semiquantitative measurement used in the clinical and research domains to assess radiopharmaceutical concentration in tumors versus normal organs, but is susceptible to many factors beyond the tumor biological environment. So, the aim of this study is to identify the optimum internal reference among organs with physiological uptake in 68Ga-DOTATATE PET/CT (DOTA PET/CT) scans. MATERIALS AND METHODS: This HIPAA-compliant, IRB-approved study with waiver of consent included retrospective imaging review of 180 consecutive patients with neuroendocrine tumors presenting for DOTA PET/CT image acquisition: Ga-68 DOTATATE dose was reported as (0.054 mCi/Kg) scans between September 2018 and May 2019. Mean value of body weight normalized SUV (SUVbw) and lean body mass normalized SUV (SUL) of liver and spleen were measured. Information about the patients and scan characteristics were collected. The paired Grambsch test was used to compare variance among the measured SUVs. Spearman's rank correlation coefficient was used to assess correlation between SUVs and potential patient- and scan-specific confounding factors. RESULTS: Variance of SUL was significantly lower than variance of SUVbw in both liver and spleen (p-value < 0.0001). Variances of liver SUVbw and SUL were significantly lower than the corresponding spleen SUVs. Liver SUL showed the lowest variance (3.69% ± 1.25%) among all measured SUVs. CONCLUSION: SUL is a more reproducible, less variable, and therefore more reliable quantitative measure in DOTA PET/CT scans, compared SUVbw. Among the available organs with physiological uptake, liver SUL is the optimum internal reference given the liver's larger size and uniform SUL values resulting in lower variability and better reproducibility.

Transient Ischemic Dilation of the Left Ventricle on SPECT: Correlation with Findings at Coronary CT Angiography.

UNLABELLED: Transient ischemic dilation (TID) in the setting of abnormal stress-rest cardiac SPECT myocardial perfusion imaging (MPI) has been linked with increased cardiovascular risk. However, the significance of TID in the setting of an otherwise normal SPECT MPI study has not been clearly established. In this study, cardiac CT was used to evaluate the prevalence of atherosclerotic lesions and the severity of coronary artery stenosis in patients with TID of the left ventricle with or without associated myocardial perfusion defects on SPECT MPI. METHODS: The study population consisted of 1,553 consecutive patients who had undergone both cardiac CT and SPECT MPI within 1 mo between January 1, 2006, and September 1, 2011. Patients included in the study group had a pathologic TID value defined as ≥1.18 for men and ≥1.22 for women. Coronary CT angiography was used to evaluate each coronary segment for the presence and composition of atherosclerotic plaque and the degree of coronary stenosis. TID-positive patients were compared with a 2:1 risk-factor-matched-pair control cohort without TID. RESULTS: TID was identified in 30 patients who were compared with TID-negative risk-factor-matched controls (n = 60). When compared with the TID-negative control cohort, TID-positive patients had no significant differences in the presence and extent of atherosclerosis, the degree of coronary artery stenosis, or the calcium score at cardiac CT. Similarly, there were no significant differences in these CT measures in TID-positive patients with a normal perfusion study (n = 20) when compared with TID-negative patients with a normal perfusion study (n = 48). In addition, there was no significant difference in the incidence of major adverse cardiac events when comparing both the TID-positive patients and the TID-negative control cohort and when comparing patients who were TID-positive with normal perfusion with patients who were TID-negative with normal perfusion. CONCLUSION: The presence of TID with an otherwise normal SPECT MPI study does not translate into a greater extent of coronary artery disease as assessed by cardiac CT or increased risk for future major adverse cardiac events.

Metabolic and functional characterization of human adipose-derived stem cells in tissue engineering.

BACKGROUND: The use of adipose-derived stem cells for tissue engineering involves exposing them to metabolically adverse conditions. This study examines the metabolism, proliferation, and differentiation of adipose-derived stem cells under various conditions. METHODS: Adipose-derived stem cells were cultured in 16 media conditions containing 0.6, 2.4, 4.3, or 6.1 mM glucose; 0.1, 2.5, 4.1, or 6.1 mM glutamine; and then grown in either 0.1% or 20% oxygen. Conditioned media were collected and assayed for glucose, lactate, and pyruvate. Cell proliferation and cell death were measured at several time points. Osteogenic differentiation was analyzed by alizarin red staining/quantification and alkaline phosphatase activity, measured weekly over 4 weeks. RESULTS: Adipose-derived stem cells remained metabolically active in all nutrient and oxygen conditions tested. Glucose consumption and lactate production increased under hypoxic conditions, but pyruvate consumption was jointly dependent on oxygen and glucose concentration. The 20% oxygen environment produced greater proliferation and cell death compared with the hypoxic environment. Osteogenic differentiation of adipose-derived stem cells was observed only when glucose and/or oxygen concentrations were physiologically normal to high. CONCLUSIONS: Adipose-derived stem cells are an excellent source of multipotent cells and are capable of advancing current tissue engineering methodologies. These data show that adipose-derived stem cells remain viable under adverse conditions of low glucose, glutamine, and oxygen concentrations. However, there are variable levels of differentiation in the various culture conditions, which could lead to challenges in de novo osteogenesis and other forms of tissue engineering. Therefore, these results should be used in developing specific strategies to ensure successful application of adipose-derived stem cells in bone engineering and similar applications.

Low Dose Histone Deacetylase Inhibitor, Depsipeptide (FR901228), Promotes Adenoviral Transduction in Human Rhabdomyosarcoma Cell Lines.

Purpose. Transduction of rhabdomyosarcoma (RMS) cells with adenoviral vectors for in vivo and in vitro applications has been limited by the low to absent levels of coxackie and adenovirus receptor (CAR). This study investigates the potential use of low doses of a histone deacetylase inhibitor, depsipeptide (FR901228), currently in Phase II human trials, to enhance adenoviral uptake in six rhabdomyosarcoma cell lines.Methods. Differences in adenoviral uptake in the presence and absence of depsipeptide (FR901228) were assessed using an adenoviral construct tagged with green fluorescent protein. Changes in CAR and alpha(v) integrin expression RMS in response to pretreatment with depsipeptide (FR901128) was determined using RT-PCR.Results. Pretreatment of five of six RMS cell lines with 0.5 ng/ml of depsipeptide (FR901228) for 72 h resulted in increased viral uptake as assessed by green fluorescent protein expression. RT-PCR analysis for CAR showed that in four of these five cell lines, CAR expression was increased 2.8-8.1-fold in cells treated with depsipeptide (FR901228) as compared to control. alpha(v) integrin expression was substantially increased in the one cell line, RH5, which showed increased GFP expression in response to depsipeptide (FR901228) pretreatment but a minimal increase in CAR expression.Conclusions. Depsipeptide (FR901228) can be used as a vehicle to enhance adenoviral transduction in a majority of RMS cells. The mechanism of increased viral uptake appears to mediate via upregulation of CAR.