The rationale was to develop recommendations on the use of 18 F-FDG PET in breast, colorectal, esophageal, head and neck, lung, pancreatic, and thyroid cancer; lymphoma, melanoma, and sarcoma; and unknown primary tumor. Outcomes of interest included the use of 18 F-FDG PET for diagnosing, staging, and detecting the recurrence or progression of cancer. Methods: A search was performed to identify all published randomized controlled trials and systematic reviews in the literature. An additional search was performed to identify relevant unpublished systematic reviews. These publications comprised both retrospective and prospective studies of varied methodologic quality. The anticipated consequences of false-positive and false-negative tests when evaluating clinical usefulness, and the impact of 18 F-FDG PET on the management of cancer patients, were also reviewed. Results and Conclusion: 18 F-FDG PET should be used as an imaging tool additional to conventional radiologic methods such as CT or MRI; any positive finding that could lead to a clinically significant change in patient management should be confirmed by subsequent histopathologic examination because of the risk of false-positive results. 18 F-FDG PET should be used in the appropriate clinical setting for the diagnosis of head and neck, lung, or pancreatic cancer and for unknown primary tumor. PET is also indicated for staging of breast, colon, esophageal, head and neck, and lung cancer and of lymphoma and melanoma. In addition, 18 F-FDG PET should be used to detect recurrence of breast, colorectal, head and neck, or thyroid cancer and of lymphoma. PET is an imaging technique that provides unique information about the molecular and metabolic changes associated with disease. The technology has existed for more than 30 years but has been used clinically for only the last 10-15 years. In this period, dramatic improvements in technology, the routine availability of medical cyclotrons (to produce the necessary short-lived positron emitters), and favorable reimbursement decisions in the late 1990s have led to a tremendous increase in the use of this technology. The major area of clinical application is currently in oncology, with some application in cardiology and neurology.PET requires the use of molecules (radiopharmaceuticals) that are labeled with radioactive nuclides. The amounts of radiolabeled material administered are extremely small (10 26 -10 29 g) and have essentially no pharmacologic effect. In this regard, PET has the unique ability to assess molecular alterations associated with disease without perturbing or altering the fundamental underlying molecular and biochemical processes. Although the number of molecular probes that can be radiolabeled with positron emitters is extremely large, and clinical investigational uses number in the thousands, clinical practice has been limited principally to the use of a glucose analog labeled with the positron emitter 18 F-FDG. 18 F-FDG was first synthesized in 1978 (1) and has become the most commonly used radioph...

Positron emission tomography (PET) provides metabolic information that has been documented to be useful in patient care. The properties of positron decay permit accurate imaging of the distribution of positron-emitting radiopharmaceuticals. The wide array of positron-emitting radiopharmaceuticals has been used to characterize multiple physiologic and pathologic states. PET is used for characterizing brain disorders such as Alzheimer disease and epilepsy and cardiac disorders such as coronary artery disease and myocardial viability. The neurologic and cardiac applications of PET are not covered in this review. The major utilization of PET clinically is in oncology and consists of imaging the distribution of fluorine 18 fluorodeoxyglucose (FDG). FDG, an analogue of glucose, accumulates in most tumors in a greater amount than it does in normal tissue. FDG PET is being used in diagnosis and follow-up of several malignancies, and the list of articles supporting its use continues to grow. In this review, the physics and instrumentation aspects of PET are described. Many of the clinical applications in oncology are mature and readily covered by third-party payers. Other applications are being used clinically but have not been as carefully evaluated in the literature, and these applications may not be covered by third-party payers. The developing applications of PET are included in this review.

a-Particle-emitting radionuclides, such as 211 At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of the much shorter range and more potent cytotoxicity of a-particles than of b-particles, 211 At-labeled agents may be ideal for the eradication of tumor cells remaining after surgical debulking of malignant brain tumors. The main goal of this study was to investigate the feasibility and safety of this approach in patients with recurrent malignant brain tumors. Methods: Chimeric antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71-347 MBq of 211 At by use of N-succinimidyl 3-[ 211 At]astatobenzoate. Eighteen patients were treated with 211 At-labeled ch81C6 ( 211 At-ch81C6) administered into a surgically created resection cavity (SCRC) and then with salvage chemotherapy. Serial g-camera imaging and blood sampling over 24 h were performed. Results: A total of 96.7% 6 3.6% (mean 6 SD) of 211 At decays occurred in the SCRC, and the mean blood-pool percentage injected dose was #0.3. No patient experienced dose-limiting toxicity, and the maximum tolerated dose was not identified. Six patients experienced grade 2 neurotoxicity within 6 wk of 211 At-ch81C6 administration; this neurotoxicity resolved fully in all but 1 patient. No toxicities of grade 3 or higher were attributable to the treatment. No patient required repeat surgery for radionecrosis. The median survival times for all patients, those with glioblastoma multiforme, and those with anaplastic astrocytoma or oligodendroglioma were 54, 52, and 116 wk, respectively. Conclusion: This study provides proof of concept for regional targeted radiotherapy with 211 At-labeled molecules in oncology. Specifically, the regional administration of 211 At-ch81C6 is feasible, safe, and associated with a promising antitumor benefit in patients with malignant central nervous system tumors.

SUMMARY. To characterize the hemodynamic factors that regulate stroke volume during upright exercise in normal man, 24 asymptomatic male volunteers were evaluated by simultaneous right heart catheterization, radionuclide angiography, and expired gas analysis during staged upright bicycle exercise to exhaustion. From rest to peak exercise, oxygen consumption increased from 0.33 to 2.55 liters/min (7.7-fold), cardiac index increased from 3.0 to 9.7 liters/min per m 2 (3.2-fold), and arteriovenous oxygen difference increased from 5.8 to 14.1 vol% (2.5-fold). The increase in cardiac index resulted from an increase in heart rate from 73 to 167 beats/min (2.5-fold), and an increase in left ventricular stroke volume index from 41 to 58 ml/m 2 (1.4-fold). During low levels of exercise, there was a linear increase in cardiac index due to an increase in both heart rate and stroke volume index; stroke volume index increased as a result of an increase in left ventricular filling pressure and end-diastolic volume index and, to a much smaller extent, a decrease in end-systolic volume index. During high levels of exercise, further increases in cardiac index resulted entirely from an increase in heart rate, since stroke volume index increased no further. Left ventricular end-diastolic volume index decreased despite a linear increase in pulmonary artery wedge pressure; stroke volume index was maintained by a further decrease in endsystolic volume index. The degree to which stroke volume index increased during exercise in individuals correlated with the change in end-diastolic volume index (r = 0.66) but not with the change in end-systolic volume index (r = 0.07). Thus, the mechanism by which left ventricular stroke volume increases during upright exercise in man is dependent upon the changing relationship between heart rate, left ventricular filling, and left ventricular contractility. At low levels of exertion, an increase in left ventricular filling pressure and end-diastolic volume are important determinants of the stroke volume response through the Starling mechanism. At high levels of exertion, the exercise tachycardia is accompanied by a decrease in end-diastolic volume despite a progressive increase in filling pressure, so that stroke volume must be maintained by a decrease in end-systolic volume. (Cire Res 58: 281-291, 1986)

The cardiovascular and behavioral adaptations associated with a 4-month program of aerobic exercise training were examined in 101 older men and women (mean age = 67 years). Subjects were randomly assigned to an Aerobic Exercise group, a Yoga and Flexibility control group, or a Waiting List control group. Prior to and following the 4-month program, subjects underwent comprehensive physiological and psychological evaluations. Physiological measures included measurement of blood pressure, lipids, bone density, and cardiorespiratory fitness including direct measurements of peak oxygen consumption (VO2) and anaerobic threshold. Psychological measures included measures of mood, psychiatric symptoms, and neuropsychological functioning. This study demonstrated that 4 months of aerobic exercise training produced an overall 11.6% improvement in peak VO2 and a 13% increase in anaerobic threshold. In contrast, the Yoga and Waiting List control groups experienced no change in cardiorespiratory fitness. Other favorable physiological changes observed among aerobic exercise participants included lower cholesterol levels, diastolic blood pressure levels, and for subjects at risk for bone fracture, a trend toward an increase in bone mineral content. Although few significant psychological changes could be attributed to aerobic exercise training, participants in the two active treatment groups perceived themselves as improving on a number of psychological and behavioral dimensions.

Alzheimer disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. Current consensus statements have emphasized the need for early recognition and the fact that a diagnosis of AD can be made with high accuracy by using clinical, neuropsychologic, and imaging assessments. Magnetic resonance (MR) or computed tomographic (CT) imaging is recommended for the routine evaluation of AD. Coronal MR images can be useful to document or quantify atrophy of the hippocampus and entorhinal cortex, both of which occur early in the disease process. Both volumetric and subtraction MR techniques can be used to quantify and monitor dementia progression and rates of regional atrophy. MR measures are also increasingly being used to monitor treatment effects in clinical trials of cognitive enhancers and antidementia agents. Positron emission tomography (PET) and single photon emission CT offer value in the differential diagnosis of AD from other cortical and subcortical dementias and may also offer prognostic value. In addition, PET studies have demonstrated that subtle abnormalities may be apparent in the prodromal stages of AD and in subjects who carry susceptibility genes. PET ligands are in late-stage development for demonstration of amyloid plaques, and human studies have already begun. Functional MR-based memory challenge tests are in development as well.

This large, prospective, nationally representative registry of elderly cancer patients found that physicians often change their intended management on the basis of PET scan results across the full spectrum of its potential uses.

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