(11)C-Choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients.

PURPOSE: To evaluate, in prostate cancer (PCa) patients the potential of (11)C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. METHODS: We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA0) who showed pathological findings on (11)C-choline PET/CT only at the LN site. (11)C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT0). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT0 were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA1) and compared with PSA0 to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT1) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. RESULTS: PET/CT0 revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA0, PSA1 (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT1, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic response, 3 progression of disease and 2 stable disease. HTT with SIB was well tolerated in all patients. Grade 3 acute toxicity in the genitourinary tract was observed in two patients. CONCLUSION: (11)C-Choline PET/CT is a valuable tool for planning and monitoring HTT in LN relapse after primary treatment. High-dose hypofractionated (11)C-choline PET/CT-guided HTT with SIB is well tolerated and is associated with a high early biochemical response rate.

Predictive value of pre-therapy (18)F-FDG PET/CT for the outcome of (18)F-FDG PET-guided radiotherapy in patients with head and neck cancer.

PURPOSE: The aim of this study was to evaluate the predictive role of pre-therapy fluorodeoxyglucose (FDG) uptake parameters of primary tumour in head and neck cancer (HNC) patients undergoing intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) on FDG-positive volume-positron emission tomography (PET) gross tumour volume (PET-GTV). METHODS: This retrospective study included 19 patients (15 men and 4 women, mean age 59.2 years, range 23-81 years) diagnosed with HNC between 2005 and 2011. Of 19 patients, 15 (79 %) had stage III-IV. All patients underwent FDG PET/CT before treatment. Metabolic indexes of primary tumour, including metabolic tumour volume (MTV), maximum and mean standardized uptake value (SUVmax, SUVmean) and total lesion glycolysis (TLG) were considered. Partial volume effect correction (PVC) was performed for SUVmean and TLG estimation. Correlations between PET/CT parameters and 2-year disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were assessed. Median patient follow-up was 19.2 months (range 4-24 months). RESULTS: MTV, TLG and PVC-TLG predicting patients' outcome with respect to all the considered local and distant disease control endpoints (LRFS, DMFS and DFS) were 32.4 cc, 469.8 g and 547.3 g, respectively. SUVmean and PVC-SUVmean cut-off values predictive of LRFS and DFS were 10.8 and 13.3, respectively. PVC was able to compensate errors up to 25 % in the primary HNC tumour uptake. Moreover, PVC enhanced the statistical significance of the results. CONCLUSION: FDG PET/CT uptake parameters are predictors of patients' outcome and can potentially identify patients with higher risk of treatment failure that could benefit from more aggressive approaches. Application of PVC is recommended for accurate measurement of PET parameters.

Role of 18F-FDG PET in the management of gestational trophoblastic neoplasia.

PURPOSE: Gestational trophoblastic neoplasia (GTN) is a rare and aggressive tumour that is usually sensitive to chemotherapy. The usefulness of conventional imaging modalities in evaluating treatment response is limited, mainly due to the difficulty in differentiating between residual tumour tissue and necrosis. The aim of the present study was to evaluate the role of FDG PET or PET/CT in primary staging and in monitoring treatment efficacy. The effect of FDG PET and combined PET/CT on the management of patients with GTN was also evaluated comparing the differences between standard treatments based on conventional imaging and alternative treatments based on PET. METHODS: This retrospective study included 41 patients with GTN referred to San Raffaele Hospital between 2002 and 2010. All patients were studied by either PET or PET/CT in addition to conventional imaging. Of the 41 patients, 38 were evaluated for primary staging of GTN and 3 patients for chemotherapy resistance after first-line chemotherapy performed in other Institutions. To validate the PET data, PET and PET/CT findings were compared with those from conventional imaging, including transvaginal ultrasonography (TV-US) in those with uterine disease, CT and chest plain radiography in those with lung disease and whole-body CT in those with systemic metastases. Conventional imaging was considered positive for the presence of uterine disease and/or metastases when abnormal findings relating to GTN were reported. PET and PET/CT were considered concordant with conventional imaging when metabolic active disease was detected at the sites corresponding to the pathological findings on conventional imaging. In addition, in 12 of the 41 patients showing extrauterine disease, FDG PET/CT was repeated to monitor treatment efficacy, in 8 after normalization of beta human chorionic gonadotropin (ßHCG) and in 4 with ßHCG resistance. In some patients, PET or PET/CT findings led to an alternative nonconventional treatment, and this was considered a change in patient management for the study analysis. RESULTS: When compared to TV-US, chest radiography and CT for staging, PET showed a concordance in 91 %, 84 % and 81 % of patients, respectively. In 8 of the 41 patients with extrauterine disease during staging, PET/CT showed a complete response to therapy after ßHCG normalization. PET and PET/CT identified the sites of persistent disease in all seven high-risk patients with ßHCG resistance, of whom four underwent second-line chemotherapy, two surgical removal of resistant disease instead of additional chemotherapy, and one surgical removal of resistant disease and second-line chemotherapy with subsequent negative ßHCG. CONCLUSION: In staging, PET cannot replace conventional imaging and does not show any information in addition to that shown by conventional imaging. The additional value of PET/CT in GTN with respect to conventional imaging is found in patients with high-risk disease. PET can identify the sites of primary and/or metastatic disease in patients with persistent high levels of ßHCG after first-line chemotherapy and may be of additional value in patient management for guiding alternative treatment.

Transversus abdominis release with biosynthetic mesh for large ventral hernia repair: a 5-year analysis of clinical outcomes and quality of life.

INTRODUCTION: Transversus abdominis release (TAR) may provide an optimal plane for mesh placement for large ventral hernias requiring medial myofascial flap advancement. Long-term outcomes of TAR for large ventral hernia repair (VHR) remains under-studied. This study aims to assess longitudinal clinical outcomes and quality of life (QoL) following large VHR with TAR and resorbable biosynthetic mesh. METHODS: Retrospective review of clinical outcomes and prospective QoL was performed for patients undergoing VHR with poly-4-hydroxybutyrate mesh and TAR from 2016 to 2021. Patients with ≤ 24 months of follow-up, defects ≤ 150 cm2, and parastomal hernias were excluded. Cost-related data was collected for each patient's hospital course. QoL was compared using paired Wilcoxon signed-rank tests. RESULTS: Twenty-nine patients met inclusion criteria. Median age and BMI were 61 years (53.2-68.1 years) and 31.4 kg/m2 (26.1-35.3 kg/m2). Average hernia defect was 390cm2 ± 152.9 cm2. All patients underwent previous abdominal surgery and were primarily Ventral Hernia Working Group 2 (58.6%). Two hernia recurrences (6.9%) occurred over the median follow-up period of 63.1 months (IQR 43.7-71.3 months), with no cases of mesh infection or explantation. Delayed healing and seroma occurred in 27 and 10.3% of patients, respectively. QoL analysis identified a significant improvement in postoperative QoL (p < 0.005), that continued throughout the 5-year follow-up period, with a 41% overall improvement. Cost analysis identified the hospital revenue generated was approximately equal to the direct costs of patient care. Higher costs were associated with ASA class and length of stay (p < 0.05). CONCLUSION: Large VHR with resorbable biosynthetic mesh and TAR can be performed safely, with a low recurrence and complication rate, acceptable hospital costs, and significant improvement in disease-specific QoL at long-term follow-up.

Antiproliferative and proapoptotic effects of viable or heat-killed Lactobacillus paracasei IMPC2.1 and Lactobacillus rhamnosus GG in HGC-27 gastric and DLD-1 colon cell lines.

Data from literature suggest the possible use of probiotics as chemopreventive agents against colon cancer, but few investigations are available on their effects on gastric cancer proliferation. In our previous study, a specific Lactobacillus, strain L. paracasei IMPC2.1, was demonstrated to colonize the human gut and positively affect fecal bacteria and biochemical parameters. The aims of the present study were to investigate the effects of L. paracasei IMPC2.1, comparing them with those of Lactobacillus rhamnosus GG (L.GG), either as viable or heat-killed cells, on cell proliferation and apoptosis in a gastric cancer (HGC-27) and a colorectal cancer cell line (DLD-1). Both the gastric and colon cancer cells were sensitive to the growth inhibition and apoptosis induction by both viable or heat-killed cells from L. paracasei IMPC2.1 and L.GG. These findings suggest the possibility for a food supplement, based on dead probiotics, including L. paracasei IMPC2.1 cells, which could represent an effective component of a functional food strategy for cancer growth inhibition, with potential for cancer prevention.

Performance measurements for the PET/CT Discovery-600 using NEMA NU 2-2007 standards.

PURPOSE: The aim of this study was to assess the performance measurements of the new PET/CT system Discovery-600 (D-600, GEMS, Milwaukee, WI). METHODS: Performance measures were obtained with the National Electrical Manufacturers Association (NEMA) NU 2-2007 procedures. RESULTS: The transverse (axial) spatial resolution FWHMs were 4.9 (5.6) mm and 5.6 (6.4) mm at 1 and 10 cm off axis, respectively. The sensitivity (average at 0 and 10 cm) was 9.6 cps/kBq. The scatter fraction was 36.6% (low energy threshold: 425 keV). The NEC peak rate (k=1) was 75.2 kcps at 12.9 kBq/cc. The hot contrasts for 10, 13, 17, and 22 mm spheres were 41%, 51%, 62%, and 73% and the cold contrasts for 28 and 37 mm spheres were 68% and 72%. CONCLUSIONS: The Discovery-600 has good performance for the NEMA NU 2-2007 parameters, particularly in improved sensitivity compared to the scanners of the same Discovery family, D-ST and D-STE.

An evaluation of clinical and quality of life outcomes after ventral hernia repair with poly-4-hydroxybutyrate mesh.

PURPOSE: Despite continued efforts, recurrence after ventral hernia repair (VHR) remains a common problem. Biosynthetic Phasix™ (Poly-4-Hydroxybutyrate, P4HB) mesh combines the durability of synthetic mesh with the bio-resistance of biologics. P4HB has shown promising early outcomes, but long-term data are lacking. We examine patients following VHR with P4HB with at least 3 years of follow-up to assess clinical and patient reported outcomes (PROs). METHODS: Adult patients (≥ 18 years old) undergoing VHR with P4HB mesh between 10/2015 and 01/2018 by a single surgeon were retrospectively identified. Patients with < 36 months of follow-up were excluded unless they had a documented recurrence. Clinical outcomes and quality of life using the Hernia-Related Quality of Life Survey (HerQLes) were assessed. RESULTS: Seventy-one patients were included with a median age and body mass index of 61.2 and 31 kg/m2, respectively. Mesh was placed in the retromuscular (79%) and onlay (21%) planes with 1/3 of patients having hernias repaired in contaminated fields. There were no mesh infections, enterocutaneous fistulas, or mesh explantations. Nine patients (12.7%) developed recurrence at a median follow-up of 43.1 months [38.2-49.1]. Mesh plane, fixation technique, and Ventral Hernia Working Group were not associated with recurrence. Significant improvement in disease-specific PROs was observed and maintained at 3-year follow-up. CONCLUSION: Longitudinal clinical and quality of life outcomes after clean and contaminated VHR with P4HB are limited. Here, we conclude that P4HB is an effective and versatile mesh option for use in abdominal wall reinforcement.

Risk factors, outcomes, and complications associated with combined ventral hernia and enterocutaneous fistula single-staged abdominal wall reconstruction.

PURPOSE: To compare two cohorts of patients; those with isolated ventral hernias (VH) and those with VH and enterocutaneous fistulas (ECF). Risk factors for surgical complications (including recurrent ECF) and outcomes during single-stage VH with ECF surgical reconstruction were analyzed. METHODS: A retrospective review was performed from 2008 to 2019. We compared two cohorts of patients with single-stage VH repairs: (1) ventral hernia repair alone (hernia alone), and (2) combined VH repair and ECF repair (hernia plus ECF). Inclusion criteria were patients ≥ 18 years of age with pre-operative VH either with or without an ECF, who underwent open hernia repair and ECF repair in a single-stage operation, with a minimum follow-up of 12 months. Patient risk factors, operative characteristics, outcomes and surgical-site complications were compared using univariate and multivariate analyses. RESULTS: We included 442 patients (hernia alone = 401; hernia plus ECF = 41) with a median follow-up of 22 months (12-96). Hernia plus ECF patients were more likely to have inflammatory bowel disease (IBD)(OR 4.4, 95% CI 1.1-17.5, p = 0.037), a history of abdominal wound infections (OR 3.4, 95% CI 1.5-7.9, p = 0.004), reoperations (OR 4.9, 95% CI 1.6-15.4, p = 0.006), superficial soft tissue infections (OR 2.5, 95% CI 1.1-6.1, p = 0.044) and hematomas (OR 8.4, 95% CI 1.2-58.8, p = 0.031), compared to hernia alone patients. ECF recurrence was associated with diabetes mellitus (DM) (n = 8, 73% vs. n = 6, 20%; p = 0.003) and surgical-site complications (n = 10, 91% vs. n = 16, 53%; p = 0.048), compared to ECF resolution. CONCLUSION: Risk factors for developing ECF were IBD and history of abdominal wound infections. Single-staged combined ECF reconstruction was associated with reoperations, soft tissue infections and hematomas. DM and surgical-site complications were associated with ECF recurrence.

Positron emission tomography/computed tomography introduction in the clinical management of patients with suspected recurrence of ovarian cancer: a cost-effectiveness analysis.

Aim of this study was to evaluate the economic impact of the introduction of positron emission tomography/computed tomography (PET/CT) in the early detection of recurrent ovarian cancer through a cost-effectiveness analysis of different diagnostic strategies. Thirty-two consecutive patients with suspected ovarian cancer recurrence, studied by both contrast enhanced abdominal CT and PET/CT, were retrospectively included in the study. Three different diagnostic strategies were evaluated and compared: (1) CT only or baseline strategy; (2) PET/CT for negative CT or strategy A; (3) PET/CT for All or strategy B. For each one, expected costs, avoided surgery and incremental cost-effectiveness ratio (ICER) were calculated to identify the most cost-effective strategy. The number of positive patients increased from baseline strategy (20/32) to strategy A and B (30/32 and 29/32 respectively). Positron emission tomography/computed tomography reoriented physician choice in 31% and 62% of patients (strategies A and B respectively). Strategy A is dominated by strategy B, which is more expensive (2909 euro vs. 2958 euro), but also more effective (3 cases of surgery avoided) and presents an ICER of 226.77 euro per surgery avoided (range: 49.50-433.00 euro). Positron emission tomography/computed tomography introduction in this population is cost-effective and allowed to redirect the clinical management of patients towards more appropriate therapeutic choices.

Cutting through the fat: a retrospective analysis of clinical outcomes, cost, and quality of life with the addition of panniculectomy to ventral hernia repair in overweight patients.

BACKGROUND: Due to the increased prevalence of overweight patients with ventral hernia, abdominal wall reconstruction combining ventral hernia repair (VHR) with panniculectomy (VHR-PAN) in overweight patients is increasingly considered. We present a retrospective comparison between VHR-PAN and VHR alone in overweight patients by examining costs, clinical outcomes, and quality of life (QoL). METHODS: Patients with body mass index (BMI) > 25.0 kg/m2 underwent VHR-PAN or VHR alone between September 2015 and May 2017 with a single surgeon and were matched into cohorts by BMI and age (n = 24 in each cohort). QoL was assessed using the Hernia-related Quality of Life Survey (HerQLes). Cost was assessed using billing data. Statistical analyses were performed using Fisher's exact tests, Mann-Whitney U tests, and regression modeling. RESULTS: Hernia defect size (p = 0.127), operative time (p = 0.140), mesh placement (p = 0.357), and recurrence rates (p = 0.156) did not vary significantly between cohorts at average follow up of one year. 60% of patients completed QoL surveys, with 61% net improvement in VHR-PAN postoperatively (p = 0.042) vs 36% in VHR alone (p = 0.054). Mean total hospitalization costs were higher for VHR alone (p = 0.019). Regression modeling showed no significant independent contribution of procedure performed due to differences in cost, wound complications, or hernia recurrence. CONCLUSIONS: At mean follow up of 2 years, VHR-PAN patients reported a comparable increase in QoL to those who received VHR alone without significantly different cost and complication rates. Concurrent VHR-PAN may therefore be a safe approach for overweight patients presenting with hernia and excess abdominal skin.

Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment.

BACKGROUND: Pharmacological and postmortem investigations suggest that patients with major depressive disorder have alterations in function or density of brain serotonin1A (5-HT1A) receptors. The aim of the present study was to use positron emission tomography with the selective 5-HT1A receptor antagonist [11C]WAY-100635 to measure 5-HT1A receptor binding in depressed patients before and during treatment with selective serotonin reuptake inhibitors. METHODS: Positron emission tomographic scans with [11C]WAY-100635 were performed on 25 patients with major depressive disorder. These included 15 unmedicated depressed patients. Ten of these unmedicated patients were scanned again during selective serotonin reuptake inhibitor treatment. A further 10 patients with major depressive disorder were scanned on one occasion only while taking selective serotonin reuptake inhibitors. Comparisons were made with [11C]WAY-100635 positron emission tomographic scans in 18 healthy volunteer subjects. Region of interest analysis and statistical parametric mapping were performed on binding potential images generated using a reference tissue model. RESULTS: Binding potential values were reduced across many of the regions examined, including frontal, temporal, and limbic cortex in both unmedicated and medicated depressed patients compared with healthy volunteers. Binding potential values in medicated patients were similar to those in unmedicated patients. CONCLUSIONS: Major depressive disorder is associated with a widespread reduction in 5-HT1A receptor binding. This reduced 5-HT1A receptor binding was not changed by selective serotonin reuptake inhibitor treatment.

Bone metabolic activity measured with positron emission tomography and [18F]fluoride ion in renal osteodystrophy: correlation with bone histomorphometry.

We evaluated the bone metabolic activity in patients with renal osteodystrophy using positron emission tomography and [18F]fluoride ion. Eight patients had secondary hyperparathyroidism (HPT), and three had low-turnover bone disease. Eleven normal subjects were also studied, and three of the eight HPT patients were reevaluated after therapy. A rate constant (K) describing the net transport of [18F] fluoride ion into a bound compartment in bone was calculated using both a three-compartment model and Patlak graphical analysis. Values of K were compared with biochemical data and with histomorphometric indices. The results indicate that K is significantly higher (P < 0.01) in HPT patients than in normal subjects and patients with low-turnover bone disease. Values of K correlated with serum alkaline phosphatase (r = 0.81) and PTH (r = 0.93) levels and with histomorphometric indices of bone formation rate (r = 0.84, P < 0.01) and eroded perimeter (r = 0.77, P < 0.05). Values of K decreased by 40 and 30%, respectively, in two patients who underwent parathyroidectomy and medical therapy. Positron emission tomography studies of bone using [18F]fluoride ion can differentiate low turnover from high turnover lesions of renal osteodystrophy and provide quantitative estimates of bone cell activity that correlate with histomorphometric data.

Errors introduced by tissue heterogeneity in estimation of local cerebral glucose utilization with current kinetic models of the [18F]fluorodeoxyglucose method.

The effects of tissue heterogeneity on the estimation of regional cerebral glucose utilization (rCMRglc) in normal humans with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) were compared with respect to the various kinetic models of the [18F]FDG method. The kinetic models were conventional homogeneous tissue models of the [18F]FDG method, with (4K Model) and without (3K Model) a rate constant to account for an apparent loss of [18F]2-fluoro-2-deoxy-D-glucose-6-phosphate ([18F]FDG-6-P), and a tissue heterogeneity model (TH Model). When either of the kinetic models designed for homogeneous tissues was applied to heterogeneous tissues, estimates of the rate constant for efflux of [18F]FDG from the tissue (k2*) and of the rate constant for phosphorylation of [18F]FDG (k3*) decreased as the duration of the experimental period was increased. When the 4K Model was used, estimates of the rate constant for the apparent dephosphorylation of [18F]FDG-6-P (k4*) were significantly greater than zero and fell with increasing duration of the experimental period. Although the TH Model included no term to describe an apparent dephosphorylation of [18F]FDG-6-P, the fit of the TH Model to the time course of total tissue radioactivity was at least as good as and often better than the fit of the 4K Model in the 120-min period following the pulse of [18F]FDG. Hence, the high estimates of k4* found in PET studies of less than or equal to 120 min can be explained as the consequence of measuring radioactivity in a heterogeneous tissue and applying a model designed for a homogeneous tissue; there remains no evidence of significant dephosphorylation of [18F]FDG-6-P in this time period. Furthermore, use of the 4K Model led to an overestimation of rCMRglc; whole-brain glucose utilization calculated with the 4K Model was greater than 20% higher than values usually obtained in normal humans by the model-independent Kety-Schmidt technique. rCMRglc was accurately estimated by the TH Model and, in experimental periods sufficiently long to minimize the effects of tissue heterogeneity, also by the original 3K Model of the deoxyglucose method.

Cortical pathophysiology and clinical neurologic abnormalities in acute cerebral ischemia. A serial study with single photon emission computed tomography.

We studied brain cortical radioactive tracer activity in a consecutive series of nine patients with acute hemispheric ischemic stroke at their first cerebral ischemic stroke at their first cerebral ischemic episode. Results from N,N,N'-trimethyl-N'- (2-hydroxy-3-methyl-5-[123-I]-iodobenzyl)-1,3 propanediamine-2HCl (four patients) and technetium Tc 99m hexamethylpropyleneamine oxime (five patients) single photon emission computed tomographic studies were compared with x-ray computed tomography (CT) and clinical findings within the first 48 hours, on day 10, and on day 30 after the clinical ictus. Cortical hypoactivity agreeing with the clinical findings was found on all initial scans but not in the follow-up studies. Cortical activity on the affected side in patients with stroke was significantly lower when compared with cortical activity in sex- and age-matched controls (n = 21). Computed tomography (with contrast) was less sensitive in detecting the ischemic lesions. These studies demonstrate that in the acute phase of stroke there is a single photon emission computed tomographic cortical disturbance that agrees with clinical findings, even when computed tomography scan infarction is limited to subcortical structures.

Technetium-99m HM-PAO-SPECT study of regional cerebral perfusion in early Alzheimer's disease.

Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropyleneamine oxime ([99mTc]HM-PAO) in sixteen patients with Alzheimer's disease (AD) in early clinical phase and in 16 healthy elderly controls. In all patients transmission computed tomography (TCT) and/or magnetic resonance imaging (MRI) did not show focal brain abnormalities. Relative to normal subjects, AD patients showed significant reductions in cortical/cerebellar activity ratio: cortical perfusion was globally depressed with the largest reductions in frontal and posterior temporo-parietal cortices. Asymmetries of relative perfusion between cerebral hemispheres were also demonstrated when language was affected or visuospatial functions were unevenly impaired. In patients with early AD, SPECT provides functional information to be compared with clinical and psychometric data.

High-resolution technetium-99m-HMPAO SPECT in patients with probable Alzheimer's disease: comparison with fluorine-18-FDG PET.

UNLABELLED: SPECT studies of regional cerebral perfusion with a high-resolution system were compared to PET studies of regional cerebral glucose utilization (rCMRglc) in 21 patients with probable Alzheimer's disease (AD). Ten normal subjects were also evaluated with SPECT and 10 with PET. METHODS: rCMRglc (for PET) and counts (for SPECT) in the associative cortices were normalized to the average rCMRglc, and counts in the calcarine cortex and basal ganglia were considered as a "reference area" to obtain a ratio. The ratio differences between patients and controls were tested with ANOVA performed separately for PET and SPECT. RESULTS: The difference between probable AD patients and controls was significant for both PET (p < 0.00001) and SPECT (p < 0.005); this difference was significant for the frontal, temporal and parietal cortices (p < 0.0001) for PET, and for the temporal (p < 0.005) and parietal (p < 0.001) cortices for SPECT. Temporo-parietal defects were detected in all subjects with PET and in 90% with SPECT. CONCLUSION: PET and SPECT are able to detect characteristic temporo-parietal abnormalities in probable AD. However, the presence of abnormalities in other associative areas is better evaluated with PET.

Evaluation of the effect of glucose ingestion and kinetic model configurations of FDG in the normal liver.

UNLABELLED: The liver plays an important role in glucose homeostasis. PET studies with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) of the liver (e.g., in neoplasms) require an understanding of the effects of dietary conditions on hepatic FDG uptake. METHODS: Twenty studies were performed on 10 normal volunteers (ages 24 +/- 4) after fasting 4 to 19 hr and again after oral consumption of 100 g of dextrose to investigate tracer kinetic model configurations of FDG in the normal liver and to evaluate the impact of oral glucose on liver in normal subjects. Dynamic PET images were acquired for about 1 hr using a Siemens/CTI 931 tomograph. RESULTS: A three-compartment model with an input function delay time parameter was the statistically preferred model configuration. The model estimated transport rate constant from plasma to liver, K1, increased significantly (p < 0.05) from 0.864 +/- 0.136 ml/min/g in fasting studies to 1.058 +/- 0.269 ml/min/g in postglucose studies. Glucose loading also significantly increased (p < 0.01) the rate constant for FDG phosphorylation, k3, from 0.005 +/- 0.003 min-1 in fasting studies to 0.013 +/- 0.007 min-1 in postglucose administration and, consequently, significantly increased both the phosphorylation fraction (k3/(k2 + k3)) and the influx constant (K1k3/(k2 + k3)). No significant differences in the liver-to-plasma transport rate constant, k2, dephosphorylation constant, k4, or distribution volume of FDG (K1/(k2 + k3)) were observed. CONCLUSION: Dynamic FDG-PET studies can be used to evaluate kinetics of liver glucose metabolism. The results indicate that dietary conditions have a significant effect on hepatic FDG kinetics. Because of the higher net FDG uptake by normal liver after glucose loading, fasting conditions are preferred for FDG liver tumor studies to increase the tumor-to-background contrast.

Clinical brain radionuclide imaging studies.

A recent survey of the knowledge and practice of both positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) of the brain among referring physicians in Europe (neurologists and psychiatrists) showed a disquieting lack of knowledge of the potential of these methodologies in the investigation and management of patients of their own specialities. The need to bring the knowledge of the potential of these techniques to the practicing physicians is paramount. It is imperative that the methodologies and concepts that preside over the application of these techniques in neurology and psychiatry must become more uniform if an impact is to be felt at a clinical level. There is clear improvement in the instrumentation available with the new state-of-the-art tomographic devices and with the development of new technetium-based radiopharmaceuticals for the study of cerebral perfusion. The constant progress made with ligands that permit the study of neurotransmission, tumor metabolism, and turnover do expand our capability to improve the knowledge concerning neurophysiology, neuropathology, and neuropharmacology of a variety of disease states. PET and SPECT will be progressively included in protocols aimed at stratifying patients with dementia, monitoring therapeutic trials, and improving our ability to determine outcome. Clinical usefulness of PET and SPECT begin to emerge in cerebral vascular disease, in the identification of cerebral death, in epilepsy, in cerebral trauma, in the investigation of HIV-positive patients with cerebral involvement, and in the monitoring of tumor recurrence and postirradiation damage. This review article outlines a current perspective of SPECT and PET as practiced in Europe, its potential, and its limitations.

The role of positron emission tomography in oncology and other whole-body applications.

Imaging and quantifying biochemical and physiological processes with PET clearly has major potential significance for all organ systems and many disease states. Although the full utility and potential of emerging new applications of PET in organs other than the heart and brain must be demonstrated in basic and clinical research studies, the rapidly accumulating aggregate experience in oncology in particular, and in other organ systems and disease states as well, indicates that PET is now truly becoming a modality of both clinical and investigative use for the body as a whole as well as for specific organ systems. Whole-body PET FDG imaging (Fig 9) illustrates the potential of biochemical imaging to map the distribution of cancer throughout the body. With the growing list of radiopharmaceutical and quantitative techniques applicable to cancer studies with PET, this field will continue to realize significant growth.

Oestrogen receptors and microsatellite instability in colorectal carcinoma patients.

About 10-15% of sporadic colorectal cancers show microsatellite instability (MIN), a mutator phenotype of mismatch repair genes. It seems that oestrogens may inhibit the pathway to colorectal carcinoma which involves a mismatch repair deficiency. Oestrogen receptorial status was evaluated in the neoplastic tissue and uninvolved surrounding mucosa of 17 MIN-positive and 33 MIN-negative tumours using an immunoenzymatic assay. MIN status was examined using the polymerase chain reaction and specific microsatellite markers. MIN was significantly associated with very low levels of oestrogen receptor in tumour tissue. Our findings suggest that MIN-positive tumours might lose a possible oestrogenic modulation mechanism.