Floro Miraldi

Positron Emission Tomography for Evaluating Para-aortic Nodal Metastasis in Locally Advanced Cervical Cancer Before Surgical Staging: A Surgicopathologic Study

PURPOSE Positron emission tomographic (PET) scanning provides a novel means of imaging malignancies. This prospective study was undertaken to evaluate PET scanning in detecting para-aortic nodal metastasis in patients with locally advanced cervical carcinoma and no evidence of extrapelvic disease before planned surgical staging lymphadenectomy. MATERIALS AND METHODS After 20 mCi of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) were administered intravenously, the abdomen and pelvis were scanned. Continuous bladder irrigation was used to reduce artifact. Patients were classified by the presence or absence of FDG uptake in the primary tumor and in pelvic or para-aortic nodes. Para-aortic node metastases were classified as present or absent according to a standardized staging procedure. Pelvic node metastases were similarly classified in a subset of patients who underwent pelvic node resection. RESULTS Thirty-two patients with stage IIB (n = 6), IIIB (n = 24), and IVA (n = 2) tumors were studied. Fluorodeoxyglucose was taken up by 91% of the cervical tumors. Six of eight patients with positive para-aortic node metastasis had PET scan evidence of para-aortic nodal metastasis. One of the two false-negatives had only one microscopic focus of metastatic cancer. In the para-aortic nodes, PET scanning had a sensitivity of 75%, a specificity of 92%, a positive predictive value of 75%, and a negative predictive value of 92%. Fluorodeoxyglucose para-aortic nodal uptake conferred a relative risk of 9.0 (95% confidence interval, 2.3 to 36.0) for para-aortic nodal metastasis. All 10 of 17 patients with metastasis were predicted by PET scanning (P < .001); five of these patients had abnormalities on computed tomographic scans. CONCLUSION Cervical cancers have a high avidity for FDG. The use of PET-FDG scanning accurately predicts both the presence and absence of pelvic and para-aortic nodal metastatic disease.

Elimination of artifactual accumulation of FDG in PET imaging of colorectal cancer

BACKGROUND Positron emission tomography (PET) with fluorine-18 labeled deoxyglucose (FDG) can detect tumor recurrences in surgical patients that are otherwise difficult to assess by CT, as well as distant metastases and small malignant nodes that are not identified by other imaging modalities. However, the evaluation of such malignancy is complicated by urinary and colonic concentrations of FDG. Methods and examples of the elimination of artifactual accumulation of FDG in PET imaging of the abdomen and pelvis are presented. METHODS Elimination of artifactual accumulation requires patient preparation that begins with cleansing of the colon using an isosmotic solution taken the evening prior to examination. Approximately 500 MBq of F-18 FDG is intravenously administered upon arrival at the PET facility and then the patient is hydrated. After administration of furosemide, a Foley catheter with a drainage bag is placed and the patient is then scanned. Just prior to scanning over the pelvis, normal saline is delivered retrogradely into the urinary bladder. At the end of scanning, the patient voids and repeated pelvic images are obtained. RESULTS These routines yield a clean scanning field. Lesions that will generally be missed because they are obscured by FDG accumulations along the colon or in the kidneys, ureters, or bladder are better visualized and identified with greater confidence. Artifacts that lead to misinterpretation also are reduced. CONCLUSION Elimination of artifactual accumulation of FDG in the colon and urinary system is essential if primary cancer, associated adenopathy, or subtle recurrences are to be evaluated in FDG PET imaging of the abdomen and pelvis.

Attention and regional cerebral blood flow in posttraumatic stress disorder patients with substance abuse histories

Performance on an attentional task was assessed in posttraumatic stress disorder patients with substance abuse histories (PTSD-SA). Positron emission tomography (PET) was used to measure concurrent regional cerebral blood flow (rCBF). Eight male PTSD-SA patients and eight normal subjects each received three serial PET scans with 15O-labeled water under the following conditions: (1) resting, (2) auditory continuous performance task (ACPT1), and (3) repeat auditory task (ACPT2). PTSD-SA patients made more errors of commission on the ACPT than normal subjects. Examination of right frontal and parietal cortex ACPT task substrates revealed decreased parietal blood flow in PTSD-SA, which may represent a pathophysiology for poor attentional task performance in PTSD-SA. Attentional problems may underlie other symptomatology in PTSD.

Neuroimaging of Vessel Amyloid in Alzheimer's Disease

ABSTRACT: Despite extensive recent advances in understanding Alzheimers disease (AD) we are unable to noninvasively establish a definite diagnosis during life and cannot monitor the cerebral deposition of amyloid β protein (A/β) in living patients. We evaluated the use of 10H3, a monoclonal antibody Fab targeting Aβ protein 1‐28 labeled with Tc‐99m. Six subjects with probable AD were studied using single‐photon emission computed tomography (SPECT) at times from 0–24 hours following injection. Curves of radioactivity in blood demonstrate a half‐life of the injected Fab of 2–3 hours. Images show uptake around the head in the scalp or bone marrow in all subjects. There is no evidence of cerebral uptake of the antibody. Scalp biopsies in all six patients demonstrate diffuse staining with 10H3 of the scalp, a pattern indistinguishable from that found in controls. Evidence of amyloid deposition in the scalp in AD is not seen with other anti‐Aβ antibodies, suggesting that 10H3 is cross‐reacting with another protein. Further studies with anti‐Aβ antibodies will require longer‐lived radionuclides to detect cerebral uptake at later tunes after injection to allow for complete clearance from the blood. Afternately, imaging using labeled Aβ itself may provide a means for noninvasive targeting of cerebral amyloid.

Measurement of Human Cerebral Blood Flow with [15O]Butanol and Positron Emission Tomography

Although H215O is widely used for CBF measurement by positron tomography, it underestimates CBF, especially at elevated flow rates. Several tracers, including butanol, overcome this problem, but the short half-life of 15O provides advantages that cause water to remain the tracer of choice. We report the first use and evaluation of 15O–labeled butanol for CBF measurement. Flow measurements made in a similar fashion with water and butanol at 10-min intervals were compared in normal volunteers under resting and hypercapnic conditions. Regional analysis showed good agreement between the tracers at low flows, and significant underestimation of flow by water relative to butanol in regions of elevated flow. The observed relationship between the tracers and the curve-fitted permeability-surface area product for water (133 ml · 100 g−1 · min−1) follow the known relationship between water and true flow. These observations indicate that [15O]-butanol provided accurate measurements of human regional CBF under conditions of elevated perfusion. We conclude that butanol is a convenient and accurate method for routine CBF determination by positron emission tomography.

Grading liposarcomas with PET using [18F]FDG

Five patients with liposarcomas of the thigh were studied using positron emission tomography (PET) with [18F]2-deoxy-2-fluoroglucose (FDG). There were three low-grade tumors (all National Cancer Institute Grade 1 myxoid liposarcomas) and two high-grade tumors (both pleomorphic liposarcomas, Grades 2 and 3). The low-grade liposarcomas were easily identified with an average dose uptake ratio (DUR) of 1.38 +/- 0.045 (mean +/- SD). The high-grade lesions were more avid for FDG with a mean DUR of 2.45 +/- 0.24. There was a significant difference (p = 0.004) in the DUR for the two groups and the histological grade of malignancy was highly correlated with the DUR for FDG (Rho = 0.89). These findings suggest that FDG-PET may be useful for distinguishing between low-grade and high-grade liposarcomas.

Preliminary report: Brain blood flow using PET in patients with posttraumatic stress disorder and substance-abuse histories

Abstract Posttraumatic stress disorder (PTSD) is defined by DSM-III-R as an anxiety disorder characterized by recurrent distressing and intrusive remembrances of a traumatic event (American Psychiatric Association 1987). Some physiological abnormalities have been found in PTSD, notably for cardiac (Blanchard et al 1991) and neuroendocrine measures (Friedman 1991), but no studies to date have directly measured regional brain function changes in PTSD using positron emission tomography (PET). This preliminary study compares PTSD patients who have histories of substance abuse (Keane et al 1983, 1988) with normal controls who did not have a history of substance abuse. PET studies of anxiety disorders (Baxter et al 1987; Nordahl et al 1989, 1990; Reiman et al 1986), and acute (London et al 1990) and recent (Volkow et al 1991) substance abuse suggested hypotheses of increased orbital frontal cortex (OFC) blood flow and decreased left/right hippocampal ratios in PTSD patients with histories of substance abuse (PTSD-SA) compared to normal control subjects.

Optimal experiment design for PET quantification of receptor concentration

The mathematical models used to analyze positron emission tomography (PET) data obtained for receptor quantitation have many unknown parameters which must be estimated from the data. Obtaining unique and precise estimates of the model parameters from PET data is difficult as a result of the complex interdependence of the parameters. Here the authors address the task of estimating the concentration of myocardial beta-adrenergic receptors using unlabeled and (18)F-labeled S(-)-fluorocarazolol as the receptor ligand. For a three-injection study the authors have optimized the ligand injection times and dosages using the D-optimal criterion for estimating receptor concentration. They found that in optimizing a three-injection experimental design, the dose of ligand in the third injection approaches zero so that the optimal three-injection design is actually a two-injection experiment. Using this optimal experiment, the authors demonstrate estimates of receptor concentration that are almost five times as precise as compared to an empirically designed three-injection experiment.

Hyperventilation-Induced Reduction in Cerebral Blood Flow: Assessment by Positron Emission Tomography

The use of positron emission tomography (PET) has been well documented as a relatively noninvasive method of measuring cerebral blood flow (CBF), both globally and regionally. The utility of readily detecting alterations in CBF is apparent, particularly when applied to the evaluation of therapeutic interventions thought to influence CBF. We report the effects of hypocapnia, an experimental condition of known cerebral vasoconstriction, in ten normal volunteers. Subjects had brain blood flow evaluated utilizing H2 15O as the positron emitter before and after approximately five minutes of hyperventilation. Baseline CBF was measured as a mean ± SD of 61.2 ± 16.3 mL/min/100 g of tissue. Mean baseline arterial blood gas values were PaO2 107.4 ± 14 mm Hg, PaCO2 37.7 ± 0.89 mm Hg, and pH 7.39 (calculated from mean [H+]). Post hyperventilation, global CBF was measured as 31.1 ± 10.8 mL/min/100 g. Mean arterial blood gas values were PaO2 141.7 ± 21 mm Hg, PaCO2 19.7 ± 5 mm Hg, and pH 7.63 (calculated from mean [H+]). CBF decreased by a mean of 49.5 ± 11 percent. Data analysis using the Students t-est showed a significant change over baseline in PaCO2 (p<0.001) and CBF (p<0.001), in the hyperventilated state. Correlations were noted between the decrease in CBF and change in PaCO2 (r = 0.81) as well as between hyperventilation PaCO2 and the change in CBF (r=0.97). We conclude that, as measured by PET, CBF decreases significantly during a state of artificial hyperventilation to a degree consistent with results seen using other methods. PET appears to be a valuable tool in the assessment of interventions that could influence CBF.

PET imaging in soft tissue sarcomas

Positron emission tomography (PET) was conceived in the early years of nuclear medicine; however, until about 1980 the technology was insufficiently developed to allow its routine application. Furthermore, the high cost of construction and operation of a PET facility delayed its use in the clinical arena and also limited the number of sites available for its development. Today, only 15 years later, PET instrumentation is very sophisticated, costs are decreasing relative to other clinical studies, and clinical PET procedures are proliferating rapidly. In the last few years the application of PET to oncology has proven to be very successful, and there is now a significant literature on PET imaging of many different cancers [1–18].