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Purpose: Standardized added metabolic activity (SAM) is a PET parameter for assessing the total metabolic load of malignant processes, avoiding partial volume effects and lesion segmentation. The potential role of this parameter in the assessment of response to chemotherapy and bevacizumab was tested in patients with metastatic colorectal cancer with potentially resectable liver metastases (mCRC)., Methods: (18)F-FDG PET/CT was performed in 18 mCRC patients with liver metastases before treatment and after five cycles of FOLFOX/FOLFIRI and bevacizumab. Of the 18 patients, 16 subsequently underwent resection of liver metastases. Baseline and follow-up SUVmax, and SAM as well as reduction in SUVmax (∆SUVmax) and SAM (∆SAM) of all liver metastases were correlated with morphological response, and progression-free and overall survival (PFS and OS)., Results: A significant reduction in metabolic activity of the liver metastases was seen after chemotherapy with a median ∆SUVmax of 25.3% and ∆SAM of 94.5% (p = 0.033 and 0.003). Median baseline SUVmax and SAM values were significantly different between morphological responders and nonresponders (3.8 vs. 7.2, p = 0.021; and 34 vs. 211, p = 0.002, respectively), but neither baseline PET parameters nor morphological response was correlated with PFS or OS. Follow-up SUVmax and SAM as well as ∆SAM were found to be prognostic factors. The median PFS and OS in the patient group with a high follow-up SUVmax were 10.4 months and 32 months, compared to a median PFS of 14.7 months and a median OS which had not been reached in the group with a low follow-up SUVmax (p = 0.01 and 0.003, respectively). The patient group with a high follow-up SAM and a low ∆SAM had a median PFS and OS of 9.4 months and 32 months, whereas the other group had a median PFS of 14.7 months and a median OS which had not been reached (p = 0.002 for both PFS and OS)., Conclusion: (18)F-FDG PET imaging is a useful tool to assess treatment response and predict clinical outcome in patients with mCRC who undergo chemotherapy before liver metastasectomy. Follow-up SUVmax, follow-up SAM and ∆SAM were found to be significant prognostic factors for PFS and OS.

Purpose: The standardized added metabolic activity (SAM) is a new marker of total lesion glycolysis that avoids partial volume effect (PVE) and thresholding. SAM is calculated by drawing a volume of interest (VOI(1)) around the tumour and a larger VOI (VOI(2)) around VOI(1). Subtracting the background activity in VOI(2)-VOI(1) from VOI(1) yields SAM. If VOI(1) is set at a reasonable distance from the tumour, PVE are avoided. Phantom and initial clinical validation data are presented., Methods: Spheres of a Jaszczak phantom were filled with a 5.4, 3.64 and 2.0 times higher concentration relative to background activity and positron emission tomography (PET) data were acquired during 10 min. SAM of all spheres was expressed as a percentage of the expected value (the actual activity ratio minus 1). In 15 patients a 10-min list-mode acquisition PET study centred on their primary squamous cell carcinoma (PSCC) was performed and images of 1-10 min reconstructed. SAM1-9min values of PSCC were expressed as a percentage of SAM10min. Nineteen patients suffering from liver metastases treated with chemotherapy underwent PET/CT prior to (scan 1) and after 3-6 cycles of chemotherapy (scan 2). SAM and maximum standardized uptake values (SUV(max)) of the liver lesions on scan 1 (SAM1 and SUV(max)1) and the percentage reduction between both ΔSAM and ΔSUV(max) were related to Response Evaluation Criteria in Solid Tumors (RECIST) response., Results: For the phantom acquisitions, the mean normalized SAM/sphere volume calculated was 94.9 % (SD 5.9 %) of the expected value. In the PSCC patients, the mean difference between SAM1min and SAM10min was only 4 % (SD 5 %). SUV(max)1min and SUV(max)10min proved to be not significantly different, but the variability was slightly larger than that of SAM (SD 6.4 %). SAM1 and ΔSAM values for responders versus non-responders were, respectively, 57 (SD 119) versus 297 (SD 625) for SAM1 (p = 0.2) and 99 % (SD 3 %) versus 32 % (SD 44 %) for ΔSAM (p = 0.001). SUV(max)1 and ΔSUV(max) values in responders versus non-responders were, respectively, 3.9 (SD 2.4) versus 6.3 (SD 3.1) for SUV(max)1 (p = 0.08) and 94 % (SD 17) versus 7 % (SD 40 %) for ΔSUV(max) (p = 0.0001). The AUC of ΔSAM and ΔSUV(max) were not significantly different on receiver-operating characteristic (ROC) analysis (AUC 1.0 and 0.99, respectively, p = 0.6)., Conclusion: SAM is a promising parameter for tumour response assessment of liver metastases by means of (18)F-fluorodeoxyglucose PET.

Purpose: To give an up-to-date overview of the potential clinical utility of (18)F-labelled choline derivatives for tumour imaging with positron emission tomography., Methods: A PubMed search for (18)F-labelled choline analogues was performed. Review articles and reference lists were used to supplement the search findings., Results: (18)F-labelled choline analogues have been investigated as oncological PET probes for many types of cancer on the basis of enhanced cell proliferation. To date, studies have focused on the evaluation of prostate cancer. Available studies have provided preliminary results for detecting local and metastatic disease. Experience with (18)F-fluorocholine PET in other tumour types, including brain and liver tumours, is still limited. In the brain, excellent discrimination between tumour and normal tissue can be achieved due to the low physiological uptake of (18)F-fluorocholine. In the liver, in which there is a moderate to high degree of physiological uptake in normal tissue, malignancy discrimination may be more challenging., Conclusion: PET/CT with (18)F-fluorocholine can be used to detect (recurrent) local prostate cancer, but seems to have limited value for T (tumour) and N (nodal) staging. In patients presenting with recurrent biochemical prostate cancer, it is a suitable single-step examination with the ability to exclude distant metastases when local salvage treatment is intended. In the brain, high-grade gliomas, metastases and benign lesions can be distinguished on the basis of (18)F-fluorocholine uptake. Moreover, PET imaging is able to differentiate between radiation-induced injury and tumour recurrence. In the liver, (18)F-fluorocholine PET/CT seems promising for the detection of hepatocellular carcinoma.

Purpose: To investigate the time-dependent changes in (18)F-FDG uptake by the thymus and marrow following combination chemotherapy for lymphoma in a paediatric study population., Methods: Included in the study were 27 paediatric patients who were in complete metabolic remission after chemotherapy and who underwent off-therapy follow-up with serial whole-body PET-CT scans. A total of 142 PET-CT scans were recorded. (18)F-FDG uptake by the thymus and marrow was assessed both visually and semiquantitatively. Visual uptake was scored on the three-dimensional maximum intensity projection of the whole-body PET image according to a three-point scale. For the semiquantitative assessment, standard uptake values were measured. To find a pattern in the (18)F-FDG uptake by the thymus and marrow a moving average technique was applied., Results: Our time series analysis indicated that the marrow activity was highest at cessation of chemotherapy and declined thereafter. During an off-chemotherapy period of on average 6 months, marrow activity decreased quickly. From 6 months onward, the activity declined more slowly. The posttherapy changes in (18)F-FDG uptake by the thymus were quite different from the changes in uptake by the marrow. The lowest thymic FDG uptake was found at cessation of chemotherapy. Thereafter, thymic activity steadily increased, reached a peak on average 10 months after therapy, and then slowly decreased., Conclusion: Knowledge of the time-dependent changes in metabolic activity in the thymus and marrow is important to avoid misinterpretation of increased (18)F-FDG uptake as disease in the off-therapy setting.

This paper reviews currently available PET studies performed either to improve our understanding of the pathogenesis of HIV-1 infection or to assess the value of PET imaging in the clinical decision making of patients infected with HIV-1 presenting with AIDS-related opportunistic infections and malignancies. FDG PET has shown that HIV-1 infection progresses by distinct anatomical steps, with involvement of the upper torso preceding involvement of the lower part of the torso, and that the degree of FDG uptake relates to viral load. The former finding suggests that lymphoid tissues are engaged in a predictable sequence and that diffusible mediators of activation might be important targets for vaccine or therapeutic intervention strategies. In lipodystrophic HIV-infected patients, limited available data support the hypothesis that stavudine-related lipodystrophy is associated with increased glucose uptake by adipose tissue as a result of the metabolic stress of adipose tissue in response to highly active antiretroviral treatment (HAART). Finally, in early AIDS-related dementia complex (ADC), striatal hypermetabolism is observed, whereas progressive ADC is characterized by a decrease in subcortical and cortical metabolism. In the clinical setting, PET has been shown to allow the differentiation of AIDS-related opportunistic infections and malignancies, and to allow monitoring of side effects of HAART. However, in patients suffering from HIV infection and presenting with extracerebral lymphoma or other human malignancies, knowledge of viraemia is essential when interpreting FDG PET imaging.

Purpose: Involvement of the serotonergic system in impulsive aggression has been demonstrated in both human and animal studies. The purpose of the present study was to investigate the effect of citalopram hydrobromide (a selective serotonin re-uptake inhibitor) on the 5-HT(2A) receptor and brain perfusion in impulsive-aggressive dogs by means of single-photon emission computed tomography., Methods: The binding index of the radioligand (123)I-5-I-R91150 was measured before and after treatment with citalopram hydrobromide in nine impulsive-aggressive dogs. Regional perfusion was measured with (99m)Tc-ethyl cysteinate dimer (ECD). Behaviour was assessed before treatment and again after 6 weeks of treatment., Results: A correlation was found between decreased binding and behavioural improvement in eight out of nine dogs. The 5-HT(2A) receptor binding index was significantly reduced after citalopram hydrobromide treatment in all cortical regions but not in the subcortical area. None of the dogs displayed alterations in perfusion on the post-treatment scans., Conclusion: This study supports previous findings regarding the involvement of the serotonergic system in impulsive aggression in dogs in general. More specifically, the effect of treatment on the 5-HT(2A) receptor binding index could be demonstrated and the decreased binding index correlated with behavioural improvement.

Purpose: The aim of the study was to determine the accuracy of non-rigid nine-parameter image registrations based on 153Gd transmission computed tomography (TCT) images as compared with those based on 99mTc-ethyl cysteinate dimer (ECD) images and to assess whether normalised mutual information (NMI) or count difference (CD) should be used., Methods: TCT and ECD data were acquired in 25 randomly selected patients. Emission images were registered to an ECD template with a CD cost function. The same registration parameters were applied to the transmission images to create a TCT template. All TCT images were registered to the TCT template and the same registration parameters were applied to the ECD images. The procedure was repeated with NMI as cost function. Accuracy of both ECD-based and TCT-based registrations was assessed by comparing the normalisation parameter values and regional activities in the spatially normalised ECD images, using a mixed-model analysis of variance (ANOVA). Scheffe post hoc tests were performed., Results: No significant differences were found between ECD/CD, ECD/NMI and TCT/CD, suggesting that ECD registration can be done with either CD or NMI, and that TCT registration using CD is equally as accurate as ECD registration. The accuracy of TCT registration with NMI was lower, with discrepancies occurring in the frontal inferior region and the cerebellum. The analysis of normalisation parameters indicated that z-scaling is underestimated and yz-rotation overestimated with TCT/NMI registration., Conclusion: We conclude that ECD registrations with CD or NMI are as accurate as TCT registrations with CD and that TCT registrations with NMI should be avoided.

This review presents neuroimaging studies which have explored the functional anatomy of a variety of cognitive processes represented by the prefrontal cortex (PFC). Overall, these studies have demonstrated that standard prefrontal neuroactivation tasks recruit a widely distributed network within the brain of which the PFC consistently forms a part. As such, these results are in keeping with the notion that executive functions within the PFC rely not only on anterior (mainly prefrontal) brain areas, but also on posterior (mainly parietal) brain regions. Moreover, intervention of similar brain regions in a large number of different executive tasks suggests that higher-level cognitive functions may best be understood in terms of an interactive network of specialised anterior as well as posterior brain regions.

In the presurgical evaluation of patients with partial epilepsies, the most extensively studied functional neuro-imaging modality to define the origin of seizure onset is fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET). Generally, this technique reveals a widespread zone of interictal glucose hypometabolism in the region of the epileptogenic focus. However, the technique may miss the epileptogenic region and FDG PET abnormalities may extend beyond the seizure onset zone. Consequently, for the precise identification of epileptogenic regions more specific imaging probes than FDG are warranted. This review considers the clinical utility of iomazenil (IMZ) SPET and flumazenil (FMZ) PET for the precise localization of epileptogenic foci in partial epilepsy syndromes.

The least invasive of all surgical weight-lowering procedures is the adjustable laparoscopic gastric banding (ALGB) technique. A rare complication (0.9%-1.8% of patients) but one that may require surgical revision is leakage of the gastric banding device. This paper reports on the usefulness of technetium-99m scintigraphy for the assessment of gastric band leaks as compared with radiography. Between March 1997 and October 2001, 23 obese patients (20 women and 3 men; mean age 35 years; range 23-60 years; mean body mass index before gastric banding procedure, 39.2 kg/m(2); range 29.3-52.1 kg/m(2)) were referred for exclusion of gastric banding leakage by means of radiography and (99m)Tc-pertechnetate scintigraphy. Both procedures were performed on the same day in all patients. Two patients underwent both procedures, respectively two and three times. A total of 27 radiographic and scintigraphic examinations were performed. Radiographs were judged positive for leakage when escape of contrast agent through a defect in the gastric banding device was visualised or when indirect criteria, e.g. smooth passage of barium suspension through the stoma after injection of contrast agent, were present. Scintigraphic images were judged positive when tracer disappearance out of the banding device and uptake in the thyroid gland as well as enhancement of the gastric mucosa were observed 30 min and/or 3 h post injection. Overall sensitivity, specificity and accuracy for radiography and (99m)Tc scintigraphy were 81.8% vs 81.8%, 75% vs 100% and 77.7% vs 92.6%. Leakage from the reservoir or the connecting tube is a late complication of ALGB. The presented data suggest that (99m)Tc-pertechnetate scintigraphy is more efficient than radiography in determining the presence of such leaks.