Richard L. Wahl

Background: Absolute quantitative single-photon emission computed tomography (SPECT) has several important applications including monitoring tumor response after treatment and dose estimation for targeted radionuclide therapy treatment planning. Obtaining quantitative SPECT images in absolute activity units requires the use of a calibration factor, and the repeatability of this directly affects the repeatability of image quantification. This study focused on evaluating the factors affecting the repeatability of a calibration factor measured using a planar image of an in-air calibration source. Methods: The calibration factors calculated as part of ¹³¹I-tositumomab patient dosimetry scans used in treatment planning performed over a 4-year period were retrospectively analyzed. Raw data included total counts in whole-body images of a radioactive calibration source, the activity of the source measured in a radionuclide activity meter (often referred to as a dose calibrator), and the background count rate obtained at three time points for each patient. The count rate from extrinsic flood source acquisitions and radionuclide activity meter constancy obtained on the same day as each image were also used. The data were analyzed statistically using a mixed-effects model to determine the factors affecting variations in the measured calibration factors. Results: The global variability in the calibration factor was equal to 2.3% and was decreased by 20% to 1.8%, when the decay-corrected measurements of calibration source activity were averaged over the three time points for each patient. Camera sensitivity variation measured using a ⁵⁷Co sheet source was small and had a weak relationship to calibration factor variations. When the averaged source activity was used, the main source of variance was related to preparation and measurement of the source (77%). Radionuclide activity meter constancy had a smaller but statistically significant impact on the calibration factor. Conclusions: This study indicates that calibration factors based on planar measurements have good reproducibility. The findings of this study indicate (1) the importance of accurate and precise preparation and measurement of the calibration source activity, (2) the need to carefully control background activity during calibration factor assessment and patient data acquisition, and (3) that the calibration factor and camera sensitivity were stable over time, indicating that careful but less frequent calibration is needed.

Conventional myocardial perfusion scintigraphy with SPECT/CT or with PET/CT has been established as pivotal clinical imaging modality for the identification of hemodynamically obstructive coronary artery disease (CAD) and risk stratification of patients with suspected or known CAD. While the assessment of the relative distribution of radiotracer uptake in the left-ventricular (LV) myocardium during vasomotor stress identifies the “culprit” or most severe CAD lesion in multivessel disease, flow-limiting effects of remaining but less severe epicardial lesions may be missed. This limitation principally may be overcome by the possibility of PET/CT with radiotracer-kinetic modeling to concurrently assess left-ventricular (LV) myocardial blood flow (MBF) in ml/g/min at rest and during vasomotor stress and the resulting myocardial flow reserve (MFR). While a stress-induced regional reduction in radiotracer uptake or perfusion identifies the most advanced epicardial lesion, flow-limiting effects of the other epicardial lesions may principally be identified by regional reductions in MFR. Conversely, reductions in MFR in CAD may be appreciated as suboptimal as they reflect not only the consequences of flow-limiting effects of epicardial stenosis but also of microvascular dysfunction. The relatively low specificity of a reduced therefore MFR may hamper a clear identification of the downstream hemodynamic effects of an epicardial lesion on hyperemic coronary flow increases. In this scenario, there is increasing evidence that the PET assessment of an abnormal decrease in MBF from the base to the apex of the LV during hyperemic flows, a so-called longitudinal flow gradient, is primarily related to fluid dynamic consequences of CAD-induced diffuse luminal and/or focal narrowing of the epicardial artery. The combined evaluation of the MFR and corresponding longitudinal MBF gradient could emerge as new a novel analytic concept to further optimize the identification and characterization of hemodynamic CAD burden in multivessel disease, which, however, warrants further clinical validation.

The insulin signaling pathway is critical for the control of blood glucose levels. Brown adipose tissue (BAT) has also been implicated as important in glucose homeostasis. The effect of short-term cold exposure on this pathway in BAT has not been explored. We evaluated the effect of 4 hours of cold exposure on the insulin pathway in the BAT of rats. Whole genomic microarray chips were used to examine the transcripts of the pathway in BAT of rats exposed to 4°C and 22°C for 4 hours. The 4 most significantly altered pathways following 4 hours of cold exposure were the insulin signaling pathway, protein kinase A, PI3K/AKT and ERK/MAPK signaling. The insulin signaling pathway was the most affected. In the documented 142 genes of the insulin pathway, 42 transcripts (29.6%) responded significantly to this cold exposure with the least false discovery rate (Benjamini-Hochberg Multiple Testing: −log10 (p-value) = 7.18). Twenty-seven genes (64%) were up-regulated, including the insulin receptor (Insr), insulin substrates 1 and 2 (Irs1 and Irs2). Fifteen transcripts (36%) were down-regulated. Multiple transcripts of the primary target and secondary effector targets for the insulin signaling were also up-regulated, including those for carbohydrate metabolism. Using western blotting, we demonstrated that the cold induced higher Irs2, Irs1, and Akt-p protein levels in the BAT than in the BAT of controls maintained at room temperature, and higher Akt-p protein level in the muscle. Conclusion: this study demonstrated that 4 hours of cold exposure stimulated the insulin signaling pathway in the BAT and muscle of overnight fasted rats. This raises the possibility that acute cold stimulation may have potential to improve glucose clearance and insulin sensitivity.

The purpose of this study was to develop a noninvasive imaging test of pancreatic exocrine function. In this pilot study, 5 healthy volunteers underwent two 60-min dynamic (11)C-acetate PET studies, one before and one after intravenous secretin administration. Kinetic analysis of the pancreas was performed using a 1-compartment model and an image-derived input function. From summed images, standardized uptake values were measured from the pancreas and the liver, and the pancreas-to-liver ratio was computed. The baseline k1 and k2 data for all 5 volunteers were consistent. After secretin stimulation, the k1 and k2 significantly increased (paired t test P = 0.046 and P = 0.023, respectively). In the summed PET images, the pancreas-to-liver ratio decreased (P = 0.037). Increased (11)C-acetate activity was observed in the duodenum after secretin stimulation consistent with secretin-induced secretion. (11)C-acetate PET studies with secretin stimulation show potential as a noninvasive method for assessing pancreatic exocrine function.

Purpose To determine the diagnostic accuracy of a semiautomated ¹⁸F-FDG PET/CT measurement of total lesion glycolysis (TLG), maximum and peak standardized uptake value at lean body mass (SUL-Max and SUL-Peak), qualitative estimates of left/right nodal symmetry and FDG uptake for differentiating lymphoma from reactive adenopathy in HIV-infected patients. Methods We retrospectively analyzed 41 whole-body ¹⁸F-FDG PET/CT studies performed in HIV-infected patients for clinical reasons. The study received institutional review board approval. Of the 41 patients, 19 had biopsy-proven untreated lymphoma, and 22 with reactive adenopathy without malignancy on follow-up were used as controls. Nodal and extranodal visual qualitative metabolic scores, SUL-Max, SUL-Peak, CT nodal size, and PERCIST 1.0 threshold-based TLG and metabolic tumor volume (MTV) were determined. The qualitative intensity of nodal involvement and symmetry of uptake were compared using receiver operator curve (ROC) analysis. HIV plasma viral RNA measurements were also obtained. Results All of the quantitative PET metrics performed well in differentiating lymphoma from reactive adenopathy and performed better than qualitative visual intensity scores. The areas under the ROC curves (AUC) were significantly higher for TLG = 0.96, single SUL-Peak = 0.96, single SUL-Max = 0.97, and MTV = 0.96, compared to 0.67 for CT nodal size (p < 0.001). These PET metrics performed best in separating the two populations in aviremic patients, with AUCs of 1 (AUC 0.91 for CT nodal size). TLG, MTV, SUL-Peak and SUL-Max were more reliable markers among viremic individuals, with AUCs between 0.84 and 0.93, compared to other metrics. PET metrics were significantly correlated with plasma viral load in HIV-reactive adenopathy controls. Asymmetrical FDG uptake had an accuracy of 90.4 % for differentiating lymphoma from reactive adenopathy in HIV-infected patients. Conclusion Quantitative PET metabolic metrics as well as the qualitative assessment of symmetry of nodal uptake appear to be valuable tools for differentiating lymphoma from reactive adenopathy in HIV-infected patients using FDG PET. These parameters appear more robust in aviremic patients.

189 Background: Though prior studies have demonstrated the prognostic value of pre- and post-treatment positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer is yet to be established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiotherapy (SBRT). Methods: Thirty-two patients with LAPC received up to 3 doses of gemcitabine, followed by SBRT 6.6 Gy in 5 daily fractions, 33 Gy total, on a prospective clinical trial. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV_max and SUV_peak) on pre-SBRT PET scans were calculated using an in-house software. Disease measurability was assessed at a threshold based on the liver standard uptake value (SUV) using the equation Liver_mean + (2 * Liver_sd). Median values of PET parameters were used as cutoffs when assessing their prognostic potential through univariate and multivariate Cox regression analyses. Results: Of the 32 patients in this study, the majority were male (N=19, 59%), 65 years or older (N=21, 66%), and had tumors located in the pancreatic head (N=27, 84%). Twenty-seven patients (85%) received induction gemcitabine prior to SBRT per protocol. Median overall survival for the entire cohort was 18.8 months (95% CI, 15.7-22.0). An MTV of 26.8 cm³ or greater (HR 4.46, 95% CI 1.64 to 5.88, p < 0.003) and TLG of 70.9 cm³ or greater (HR 3.08, 95% CI 1.18 to 8.02, p < 0.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19 to 22.21, p=0.029) and TLG (HR 3.34, 95% CI 1.07 to 10.48, p=0.038) remained independent prognostic factors for overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG yield prognostic information on overall survival in patients with LAPC and may assist in tailoring therapy. Clinical trial information: NCT01146054.

A Case-Based Approach to PET/CT in Oncology describes the role of PET/CT in the diagnosis, staging and monitoring of treatment response in today's practice of oncology. It provides a detailed analysis of over 100 cases occurring in daily clinical practice, emphasizing the central role that PET imaging plays in the care of cancer patients. The text is organized into two sections; Part I guides the reader through general introductory concepts, including basic science, while Part II covers in-depth oncologic applications. Each case is illustrated throughout with full color images and explains the key management issues and the advantages and limitations of the modality. Written by a team of renowned international experts, A Case-Based Approach to PET/CT in Oncology is an invaluable resource for all imaging practitioners, oncologists and nuclear medicine specialists.